Prognostic impact of outpatient loop diuretic reduction patterns in patients with chronic heart failure.

Background: The relationship between patterns of outpatient oral loop diuretic (LD) dose reduction and prognosis in patients with heart failure (HF) remains unclear. Methods: We evaluated 679 patients with HF-prescribed LDs at baseline between September 2015 and August 2019. Dose reduction was defined as a change to a lower LD dose than the previous outpatient dose. Dose intensification was defined as a change to a higher LD dose than the previous outpatient dose. Patients were classified into no-reduction (no LD dose reduction during follow-up) and reduction groups (categorized into successive-reduction [≥2 successive LD dose reductions without intervening LD dose intensification] and single-reduction [LD dose reduction without successive dose reduction] groups). The primary outcomes were all-cause death, HF hospitalization (HFH), and the composite of cardiovascular death (CVD) or HFH. Results: Within a median follow-up of 53.7 (range, 2.6-99.1) months, 156 deaths were recorded: 121 (29 %), 31 (15 %), and three (4 %) patients in the no-reduction (n = 411), single-reduction (n = 195), and successive-reduction (n = 73) groups, respectively. After adjusting for cofounders, the reduction group had a lower risk of primary outcomes than the no reduction group (all-cause death: hazard ratio (HR) = 0.65, 95 % confidence interval (CI) = 0.44-0.96; CVD or HFH: HR=0.69, 95 %CI=0.52-0.93; HFH: HR=0.69, 95 % CI=0.52-0.93). The successive-reduction group had a lower risk of the composite of CVD or HFH (HR=0.26, 95 % CI: 0.10-0.67) and HFH (HR=0.34, 95 % CI=0.13-0.86) than the single-reduction group. Conclusions: Outpatient LD dose reduction patterns can be indicators of good prognosis in HF patients.

Diuretic dosing and outcomes with torsemide and furosemide following hospitalization for heart failure: The TRANSFORM-HF trial.

AIMS: The TRANSFORM-HF trial found no difference in clinical outcomes between torsemide versus furosemide after hospitalization for heart failure. This analysis aimed to assess the impact of diuretic dosing on the primary and secondary clinical outcomes. METHODS AND RESULTS: This post-hoc analysis of TRANSFORM-HF categorized patients into three groups by discharge diuretic dose: (1) ≤40 mg, (2) >40-80 mg, and (3) >80 mg of furosemide equivalents. The associations between discharge dose and 12-month clinical events, and change in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS), were assessed. Overall, 2379 patients were included, aged 65 years (interquartile range 56-75), 883 (37.1%) women, and 812 (34.2%) Black. Furosemide had adjusted hazard ratios (aHR) for all-cause mortality of 1.21 (95% confidence interval [CI] 0.91-1.59) for discharge dose group 2 and 1.40 (95% CI 1.04-1.88) for group 3, compared with group 1. For torsemide, aHRs were 1.74 (95% CI 1.32-2.30) for group 2 and 1.58 (95% CI 1.14-2.19) for group 3. No evidence of heterogeneity for the association between increased mortality and higher dose was found by loop diuretic type (pinteraction = 0.17). Higher doses of furosemide and torsemide were associated with increased risk of all-cause hospitalization and the composite of all-cause mortality and hospitalization, without evidence of heterogeneity by loop diuretic type (pinteraction > 0.2). Changes in KCCQ-CSS from baseline at 12 months was similar across dose groups for both drugs. CONCLUSION: Following hospitalization for heart failure, higher loop diuretic dosing was independently associated with worse clinical and patient-reported outcomes. The correlation between higher loop diuretic dose and outcomes was consistent, regardless of loop diuretic used.

The Role of Subcutaneous Furosemide in Heart Failure Management: A Systematic Review.

BACKGROUND: Acute decompensated heart failure (ADHF) patients with symptomatic congestion often require in-hospital admission for intravenous (IV) diuretic, impacting both patient well-being and healthcare expenses. Subcutaneous (SC) furosemide has a potential to facilitate outpatient management of ADHF patients. Thus, this study aims to assess the efficacy and safety of SC furosemide utilization, offering a potential alternative to traditional IV administration. METHODS: A systematic search was conducted until April 14 2024 across scientific databases. This review included studies comparing SC furosemide with oral and IV formulations in adult HF patients. RESULTS: This study analyzed 687 patients from 20 studies. The results demonstrate that SC furosemide can effectively manage symptomatic congestion in HF patients and results in significant cost reductions, symptom relief, and improved quality of life. Although further investigation into mortality rates is needed, SC furosemide demonstrates efficacy comparable to IV furosemide in diuresis and weight loss, with similar bioavailability and natriuretic effects. Adverse events are generally minor, predominantly related to skin irritation. Innovative strategies, such as developing isotonic alkaline solutions and improved infusion devices, are being explored to address these challenges. CONCLUSION: SC furosemide offers a promising alternative for managing ADHF, particularly in symptomatic HF patients with volume overload. The integration of SC furosemide into routine clinical practice and future guidelines, could optimize the management of HF, reducing hospital admission and improving patient outcomes.

The furosemide stress test predicts successful discontinuation of continuous renal replacement therapy in critically ill patients with acute kidney injury.

PURPOSE: There is still no good method for predicting renal recovery and successful discontinuation of continuous renal replacement therapy (CRRT). This study assessed the ability of the furosemide stress test (FST) to predict successful discontinuation of CRRT. MATERIALS AND METHODS: This prospective single-center study included patients with acute kidney injury who underwent an initial attempt at discontinuation of CRRT. Successful discontinuation was defined as alive without renal replacement therapy for 7 days after discontinuation. Furosemide 1.0 mg/kg was administered intravenously within 2 h after discontinuation of CRRT. Urine output was recorded for the next 2 h. Receiver-operating characteristic curve and logistic regression analyses were performed to determine the best discriminative variable and to identify independent risk factors. RESULTS: Discontinuation of CRRT was successful in 30 of 55 patients. The area under the curve for prediction of successful discontinuation was significantly greater for urine output in the 2 h following the FST (0.913) than for 24-h urine output on the previous day (0.739, P = 0.003) and urine neutrophil gelatinase-associated lipocalin (0.725, P = 0.020). A 2-h urine output of 188 mL had optimal sensitivity (0.800) and specificity (0.920). Multivariate analysis showed that 2-h urine output independently predicted successful discontinuation. CONCLUSIONS: A urine output >188 mL in the first 2 h after FST predicted successful discontinuation of CRRT.

Modified furosemide responsiveness index and biomarkers for AKI progression and prognosis: a prospective observational study.

BACKGROUND: Modified furosemide responsiveness index (mFRI) is a novel biomarker for assessing diuretic response and AKI progression in patients with early AKI. However, the comparative predictive performance of mFRI and novel renal biomarkers for adverse renal outcomes remains unclear. In a single-center prospective study, we aimed to evaluate the discriminatory abilities of mFRI and other novel renal biomarkers in predicting AKI progression and prognosis in patients with initial mild and moderate AKI (KDIGO stage 1 to 2). RESULTS: Patients with initial mild and moderate AKI within 48 h following cardiac surgery were included in this study. The mFRI, renal biomarkers (including serum or urinary neutrophil gelatinase-associated lipocalin [sNGAL or uNGAL], serum cystatin C, urinary N-acetyl-beta-D-glycosaminidase [uNAG], urinary albumin-to-creatinine ratio) and cytokines (TNF, IL-1ß, IL-2R, IL-6, IL-8, and IL-10) were measured at AKI diagnosis. The mFRI was calculated for each patient, which was defined as 2-hour urine output divided by furosemide dose and body weight. Of 1013 included patients, 154 (15.2%) experienced AKI progression, with 59 (5.8%) progressing to stage 3 and 33 (3.3%) meeting the composite outcome of hospital mortality or receipt of renal replacement therapy (RRT). The mFRI showed non-inferiority or potential superiority to renal biomarkers and cytokines in predicting AKI progression (area under the curve [AUC] 0.80, 95% confidence interval [CI] 0.77-0.82), progression to stage 3 (AUC 0.87, 95% CI 0.85-0.89), and composite outcome of death and receipt of RRT (AUC 0.85, 95% CI 0.82-0.87). Furthermore, the combination of a functional biomarker (mFRI) and a urinary injury biomarker (uNAG or uNGAL) resulted in a significant improvement in the prediction of adverse renal outcomes than either individual biomarker (all P < 0.05). Moreover, incorporating these panels into clinical model significantly enhanced its predictive capacity for adverse renal outcomes, as demonstrated by the C index, integrated discrimination improvement, and net reclassification improvement (all P < 0.05). CONCLUSIONS: As a rapid, cost-effective and easily accessible biomarker, mFRI, exhibited superior or comparable predictive capabilities for AKI progression and prognosis compared to renal biomarkers in cardiac surgical patients with mild to moderate AKI. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04962412. Registered July 15, 2021, https://clinicaltrials.gov/ct2/show/NCT04962412?cond=NCT04962412&draw=2&rank=1 .

Real world experience in effect of torsemide vs. furosemide after discharge in patients with HFpEF.

AIMS: Few studies have focused on the effect of torsemide versus furosemide after discharge on prognosis in patients with heart failure with preserved ejection fraction (HFpEF). This single-centre retrospective real-world study was conducted to evaluate the effect of torsemide versus furosemide after discharge on all-cause mortality and rehospitalization for heart failure in patients with HFpEF. METHODS: Consecutive patients who were diagnosis with HFpEF after discharge between January 2015 and April 2018 at the First Affiliated Hospital of Dalian Medical University and who had been treated with torsemide or furosemide were included in this study. The primary outcome was all-cause mortality. The second outcome was rehospitalization for heart failure. RESULTS: A total of 445 patients (mean age 68.56 ± 8.07, female 55%) were divided into the torsemide group (N = 258) or furosemide group (N = 187) based on the treatment course at discharge from the hospital. During a mean follow-up of 87.67 ± 11.15 months, death occurred in 68 of 258 patients (26.36%) in the torsemide group and 60 of 187 patients (30.09%) in the furosemide group [hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.57-1.15, P = 0.239]. Rehospitalization for heart failure occurred in 111 of 258 patients (43.02%) in the torsemide groups and 110 of 187 patients (58.82%) in the furosemide group (HR 0.64, 95% CI 0.49-0.85, P = 0.002). CONCLUSIONS: Compared with furosemide, torsemide did not significantly reduce all-cause mortality, but there was association between torsemide and reduced rehospitalization for heart failure in patients with HFpEF.

Avoiding Treatment in Hospital With Subcutaneous Furosemide for Worsening Heart Failure: A Pilot Study (AT HOME-HF).

BACKGROUND: Therapies are needed to address worsening congestion, without hospitalization, in patients with chronic heart failure (HF). OBJECTIVES: This pilot study assessed outcomes of a novel subcutaneous (SC) furosemide formulation compared to usual care in outpatients with worsening congestion. METHODS: Participants with chronic HF and worsening congestion were randomized open-label 2:1 to SC furosemide compared to usual care (UC). Decongestion was estimated by tracking body weight. The primary endpoint was a win ratio of a 30-day hierarchical composite of cardiovascular death, HF events, and change in N-terminal pro-B-type natriuretic peptide. Secondary endpoints included dyspnea severity, functional capacity, and quality of life. RESULTS: Thirty-four participants were randomized to SC furosemide and 17 to UC. SC furosemide caused greater reduction in body weight: between-group difference in least square mean change was -2.02 kg at day 3 (95% CI: -3.9 to -0.14; P = 0.035). SC furosemide-to-UC win ratio was 1.11 (95% CI: 0.48-2.50; P = 0.806). Significant between-group least square mean differences favoring SC furosemide occurred in 7-point dyspnea score (P = 0.017) and 6-minute walk test (P = 0.032), with trend in Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 Overall Summary Score of 9.15 (95% CI: 1.95-20.3; P = 0.106). The most common related adverse event with SC furosemide was mild infusion site pain (11.8%). CONCLUSIONS: SC furosemide augmented weight loss in patients with HF and worsening congestion. The composite primary endpoint was not statistically significant in this pilot investigation. However, findings of improved dyspnea scores and functional capacity, with favorable trend in KCCQ-12 score, warrant additional investigation to further document the clinical value of SC furosemide as an alternative to hospitalization (AT HOME-HF [Avoiding Treatment in the Hospital With Furoscix for the Management of Congestion in Heart Failure-A Pilot Study]; NCT04593823).

Bimetallic FeCo-MOFs mediated Au nanorods etching for the multi-colorimetric and photothermal immunosensing of illegal additive.

With the rapid expansion of the health food industry, the scope of safety supervision has also increased. However, traditional instrument detection methods cannot meet the requirements for the rapid on-site detection. Hence, the development of a rapid, precise, and simple method for the analysis of illegal additives in health foods is of great importance. In this work, by using FeCo-MOFs as mimetic peroxidase to mediate Au nanorods (Au NRs) etching, a dual-mode immunosensor based on multi-colorimetric and photothermal signals was fabricated to detect furosemide (FUR). In multi-colorimetric channel, the localized surface plasmon resonance (LSPR) peaks of Au NRs shifted blue, resulting in multi-color changes from red to gray to blue and finally to purple. In photothermal channel, the photothermal effect of Au NRs decreased, resulting in temperature changes. In the range of 1.0 × 10-5-1.0 × 10-2 µg/mL, both LSPR peak blue shift and temperature changes were linearly correlated with the logarithm of FUR concentration, with the detection limits were 4.9 × 10-6 and 8.5 × 10-6 µg/mL, respectively. Furthermore, its concentration can be accurately and intuitively assessed through the observation of vivid colorimetric changes. This advancement offers a highly promising approach for the on-site detection of FUR, facilitating timely and efficient monitoring, thereby significantly enhancing regulatory compliance and ensuring consumer safety.

Furosemide for patent ductus arteriosus during cyclooxygenase inhibitor therapy: A systematic review.

BACKGROUND: Although furosemide is used during cyclooxygenase (COX) inhibitor therapy for patent ductus arteriosus (PDA), there are concerns regarding increased ductal closure failure and acute renal failure (ARF). This systematic review explores the effects of furosemide during COX inhibitor therapy. METHODS: We searched MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi databases for randomized clinical trials that assessed furosemide during COX inhibitor therapy for PDA in preterm infants. The primary outcome measure was PDA closure failure. Mortality and other complications were also assessed. The risk of bias was assessed using the Cochrane risk-of-bias tool for randomized control trials, and the certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation criteria. RESULTS: Overall, three trials involving 121 patients were included in the analysis. The overall incidence of PDA closure failure was 28%. Although the result of PDA closure failure, mortality, and ARF were obtained, other outcomes were not described in any of the studies. The risk of bias was high. The risk of PDA closure failure did not increase with furosemide administration. Furosemide was not associated with decreased mortality but was associated with an increased risk of ARF (risk ratio, 4.96 [95% confidence interval: 1.80-13.6]). The certainty of evidence for all outcomes was very low. CONCLUSION: Although furosemide is not associated with an increased risk of PDA closure failure or mortality, the risk of ARF increases after furosemide administration during COX inhibitor therapy.

Assessment of ureteric jets as a supportive diagnostic modality for unilateral pelvi-ureteric junction obstruction and its utility in follow-up: A pilot study.

INTRODUCTION: Pelvi-Ureteric Junction Obstruction (PUJO) is a common cause of hydronephrosis (HDN) in children. While ultrasonography (USG) is useful for initial assessment and grading of hydronephrosis, it cannot differentiate obstructive from non-obstructive cases. Renal Dynamic Scintigraphy (RDS) confirms the diagnosis but involves ionizing radiation exposure. Ureteric jets using colour Doppler USG have been proposed for diagnosing obstructive HDN. OBJECTIVE: Our study aimed to evaluate Ureteric Jet Frequency (UJF) and Relative Jet Frequency (RJF) in unilateral PUJO before and after furosemide (Lasix) administration, assessing their diagnostic and post-operative utility. MATERIALS AND METHODS: Children (<14 years) with unilateral HDN underwent USG and RDS for PUJO diagnosis. Pyeloplasty was performed based on standard criteria. UJF and RJF were assessed before and after furosemide administration (0.5 mg/kg) by colour Doppler USG. The non-obstructed side was taken as the control. Follow-up included repeat RDS and ureteric jet assessment. RESULTS: Fifty-two cases were included. UJF (pre- and post-Lasix) was significantly lower in the obstructed side compared to the non-obstructed side at baseline and post-pyeloplasty (p < 0.0001). However, the baseline UJF difference between cases and controls was not significant (p > 0.05). UJF and RJF (pre- and post-Lasix) increased postoperatively. The UJF difference decreased postoperatively (p < 0.05). (attached Table) CONCLUSION: UJF and RJF are useful for diagnosing and monitoring unilateral PUJO. The effect of furosemide on UJF needs to be assessed using additional studies with larger sample sizes to understand if it can affect UJF in a way similar to that noted in diuretic scintigraphy.

Impact of natriuresis on worsening renal function during episodes of acute heart failure.

INTRODUCTION AND OBJECTIVES: Worsening renal function (WRF) is a frequent complication in acute heart failure (AHF) with a controversial prognostic value. We aimed to study the usefulness of natriuresis to evaluate WRF. METHODS: We conducted an observational, prospective, multicenter study of patients with AHF who underwent a furosemide stress test. The patients were classified according to whether WRF was present or absent and according to the median natriuretic response. The main endpoint was the combination of mortality, rehospitalization due to HF, and heart transplant at 6 months of follow-up. RESULTS: One hundred and fifty-six patients were enrolled, and WRF occurred in 60 (38.5%). The patients were divided into 4 groups: a) 47 (30.1%) no WRF/low UNa (UNa ≤ 109 mEq/L); b) 49 (31.4%) no WRF/high UNa (UNa >109 mEq/L); c) 31 (19.9%) WRF/low UNa and d) 29 (18.6%) WRF/high UNa. The parameters of the WRF/low UNa group showed higher clinical severity and worse diuretic and decongestive response. The development of WRF was associated with a higher risk of the combined event (HR, 1.88; 95%CI, 1.01-3.50; P=.046). When stratified by natriuretic response, WRF was associated with an increased risk of adverse events in patients with low natriuresis (HR, 2.28; 95%CI, 1.15-4.53; P=.019), but not in those with high natriuresis (HR, 1.18; 95%CI, 0.26-5.29; P=.826). CONCLUSIONS: Natriuresis could be a useful biomarker for interpreting and prognosticating WRF in AHF. WRF is associated with a higher risk of adverse events only in the context of low natriuresis.

Intravenous delivery of furosemide using lipid-based versus polymer-based nanocapsules: in vitro and in vivo studies.

OBJECTIVES: Furosemide (FSM), a potent loop diuretic, is used to treat edema due to hypertension, congestive heart failure, and liver and renal failures. FSM applications are limited by its low bioavailability. Our aim is to use different nanoencapsulation strategies to control the release of FSM and enhance its pharmacokinetic properties. METHODS: Two types of FSM-loaded nanocapsules, namely FSM-loaded lipid nanocapsules (LNCs) and polymeric nanocapsules (PNCs), were developed, physicochemically characterized, and subjected to pharmacokinetic and pharmacodynamic studies. Lipid nanocapsules were prepared by the simple phase inversion method using LabrafacTM lipid, while the polymeric nanocapsules were prepared by nanoprecipitation method using polycaprolactone polymer. RESULTS: Transmission electron microscopy ascertains spherical structures, corroborating the nanometric diameter of both types of nanocapsules. The particle size of the optimized FSM-loaded LNCs and FSM-loaded PNCs was 32.19 ± 0.72 nm and 230.7 ± 5.13 nm, respectively. The percent entrapment efficiency was 63.56 ± 1.40% of FSM for the optimized PNCs. The in vitro release study indicated prolonged drug release compared to drug solutions. The two loaded nanocapsules systems succeeded in enhancing the pharmacokinetic parameters in comparison to the marketed FSM solution with superior diuretic activity (p < 0.05). The results of the stability study and the terminal sterilization by autoclave indicated the superiority of LNCs over PNCs in maintaining the physical parameters under storage conditions and the drastic conditions of sterilization. CONCLUSIONS: LNCs and PNCs are considered promising nanosysems for improving the diuretic effect of FSM.

Analysis of Survival Modification by Furosemide Use in a Cohort of Hospitalized COVID-19 Patients with Severe or Critical Disease in Mexico: Due to Its Chemical Structure, Furosemide Is More than Just a Diuretic.

In the ongoing fight against Coronavirus Disease 2019 (COVID-19), researchers are exploring potential treatments to improve outcomes, especially in severe cases. This includes investigating the repurposing of existing medications, such as furosemide, which is widely available. This study aimed to evaluate the impact of furosemide on mortality rates among COVID-19 patients with severe or critical illness. We assessed a cohort of 515 hospitalized adults who experienced a high mortality rate of 43.9%. Using a multivariate analysis with adjusted risk ratios (AdRRs), factors like smoking (AdRR 2.48, 95% CI 1.53-4.01, p < 0.001), a high Pneumonia Severity Index (PSI) score (AdRR 7.89, 95% CI 5.82-10.70, p < 0.001), mechanical ventilation (AdRR 23.12, 95% CI 17.28-30.92, p < 0.001), neutrophilia (AdRR 2.12, 95% CI 1.52-2.95, p < 0.001), and an elevated neutrophil-to-lymphocyte ratio (NLR) (AdRR 2.39, 95% CI 1.72-3.32, p < 0.001) were found to increase mortality risk. In contrast, vaccination and furosemide use were associated with reduced mortality risk (AdRR 0.58, p = 0.001 and 0.60, p = 0.008; respectively). Furosemide showed a pronounced survival benefit in patients with less severe disease (PSI < 120) and those not on hemodialysis, with mortality rates significantly lower in furosemide users (3.7% vs. 25.7%). A Kaplan-Meier analysis confirmed longer survival and better oxygenation levels in patients treated with furosemide. Furthermore, a Structure-Activity Relationship analysis revealed that furosemide's sulfonamide groups may interact with cytokine sites such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), potentially explaining its beneficial effects in COVID-19 management. These findings suggest that furosemide could be a beneficial treatment option in certain COVID-19 patient groups, enhancing survival and improving oxygenation.

Magnetic molecularly imprinted polymer based on coordination for the determination of trace banned substance furosemide in human urine.

Furosemide (FUR), banned in sports events by the World Anti-Doping Agency, is a key target in drug tests, necessitating a pretreatment material capable of selectively, rapidly, and sufficiently separating/enriching analytes from complex matrices. Herein, a metal-mediated magnetic molecularly imprinted polymer (mMIP) was rationally designed and synthesized for the specific capture of FUR. The preparations involved the utilization of chromium (III) as the binding pivot, (3-aminopropyl)triethoxysilane as functional monomer, and Fe3O4 as core, all assembled via free radical polymerization. Both the morphologies and adsorptive properties of the mMIP were characterized using multiple methods. The resulting Cr(III)-mediated mMIP (ChM-mMIP) presented excellent selectivity and specificity toward FUR. Under optimized conditions, the adsorption capacity reached 128.50 mg/g within 10 min, and the imprinting factor was 10.41. Moreover, it was also successfully applied as a dispersive solid-phase extraction material, enabling the detection of FUR concentration as low as 20 ng/mL in human urine samples when coupled with a high-performance liquid chromatography/photodiode array. Overall, this study offers a valuable strategy for the development of novel recognition material.

FIRE Stones: impact of forced diuresis on the residual fragment rate after flexible ureteroscopy for destruction of kidney stones with laser-protocol for a randomized controlled two-parallel group multicenter trial with blinding evaluation.

BACKGROUND: Lithiasis is a common and recurrent disease. Flexible ureteroscopy (fURS) is the cornerstone of laser treatment of kidney stones. Kidney stones destruction requires its laser pulverization into small fragments in order to remove them through the ureter or improve their spontaneous expulsion along the urinary tract. However, most of the time, all the micro-fragments and dust created cannot be extracted using our surgical tools and may stay intra-renally at the end of the procedure. Adjuvant treatments (such as forced diuresis, inversion or mechanical pressure) were previously described to improve the expulsion of stone fragments after extra-corporeal shock wave lithotripsy. Nevertheless, the impact of adjuvant treatment after fURS remains unclear and mainly theoretical. OBJECTIVE: The primary objective is to show that the injection of 40 mg of furosemide in slow intravenous during 10 min, after the procedure, increases the stone-free rate 3 months after a fURS for destruction of kidney stones with laser. METHODS/DESIGN: The study will be a two-parallel group randomized, controlled, multicentric trial with a blinding evaluation. Nine French departments of urology will participate. Patients will be randomized in 2 groups: the experimental group (injection of 40 mg of furosemide at the end of the surgery) and a control one (usual care). Patients will be followed up for 3 months (± 2 weeks) after the surgery. Then, we will perform a low dose abdomino-pelvic CT scan. The primary outcome is the stone-free rate at 3 months. A centralized review of the images will be performed by two specialized radiologists, in a blind and crossed way to allow a homogenization of the results. The secondary outcomes will include the rate of early post-operative urinary tract infection (UTI), the evaluation of post-operative pain, and the safety of the use of furosemide in patients treated by fURS for renal stone laser destruction. As secondary objectives, it is also planned to look at the effect of the prescription of an alpha-blocker as usual treatment on stone-free rate and to assess the agreement between the imaging analysis of the urologist and the specialized radiologist. DISCUSSION: Lithiasis is a public health problem. It affects about 10% of the general population. This prevalence is increasing (multiplied by 3 in 40 years), partly due to changes in the population's eating habits over the years. The lithiasis patient is a patient with a chronic disease requiring annual follow-up and who may suffer from multiple recurrences, with a recurrence rate at 5 years of 50%. Recurrences are partly due to residual fragments left in the kidneys at the end of the operation. Other risk factors for recurrence include dietary hygiene and the presence of an associated metabolic disease. The metabolic blood and urine tests recommended by the Association Française d'Urologie (AFU) can be used to manage these last two problems. As far as residual fragments are concerned, their presence leads to an early recurrence of stones because they form the bed for a new aggregation of crystals in the kidneys. Being able to reduce the rate of residual fragments in patients with the use of furosemide at the end of the intervention therefore seems essential in the management of recurrences in our patients. This will also improve our patients' quality of life. Indeed, lithiasis disease leads to chronic pain associated with acute pain that motivates consultations to the emergency for specialized management. This study is the first to evaluate the impact of forced diuresis with the use of furosemide on the stone-free rate after a fURS for destruction of kidney stone with laser. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05916963 , first received: 22 June 2023. EU Clinical Trials Register EudraCT Number: 2022-502890-40-00.

Human Factors Validation of a Wearable, On-Body Infusor for Subcutaneous Administration of Furosemide.

Purpose: Furoscix® (subcutaneous furosemide) is administered using a wearable On-Body Infusor (OBI) and is approved for the treatment of congestion associated with heart failure (HF). The purpose of this study was to assess the safe and effective use of the OBI and Instructions for Use (IFU) by patients with HF, caregivers, and healthcare practitioners (HCPs). Methods: Sixty participants (patients, n=30; caregivers, n=15; HCPs, n=15) were evaluated on completion of OBI use tasks and IFU knowledge tasks in a simulated use environment. Fifteen of the patients received OBI/IFU training before evaluation. Results: Overall, 893/900 (99.2%) use tasks and 2211/2220 (99.6%) knowledge tasks were completed successfully, without differences due to training. The most common (n=6) use error was failure to wipe skin or cartridge tip with an alcohol wipe. Errors were due to forgetfulness/misinterpretation rather than IFU clarity. Conclusion: The subcutaneous furosemide OBI can be safely and effectively used by patients, caregivers, and HCPs, regardless of training.

Effects of Functional Biomaterials on the Attributes of Orally Disintegrating Tablets Loaded with Furosemide Nanoparticles: In Vitro and In Vivo Evaluations.

Furosemide (FUR) is a diuretic used to relieve edema, congestive heart failure, cirrhosis, end-stage renal disease, and hypertension. FUR is a class IV according to the Biopharmaceutics Classification System. It is practically insoluble in water. This study aimed to optimize and formulate porous orally disintegrating tablets (ODTs) prepared by sublimation and loaded with FUR nanoparticles prepared by using a planetary ball mill. Different functional biomaterials called stabilizers were used to stabilize the nanoparticle formula. Pluronic F-127 was the optimum stabilizer in terms of particle size (354.07 ± 6.44), zeta potential (-25.3 ± 5.65), and dissolution efficiency (56.34%). The impact of the stabilizer concentration was studied as well, and a concentration of 3% showed the smallest particle size (354.07 ± 6.44), best zeta potential value (-25.3 ± 5.65), and percentage of dissolution rate (56.34%). A FUR-loaded nanoparticle formula was successfully prepared. The nanoparticle formula was stabilized by using 3% pluronic F-127, and 3% was chosen for further study of the incorporation into oral disintegration tablets prepared by the sublimation technique. The impact of the matrix sublimating agent and superdisintegrant on the ODTs' attributes (in vitro disintegration, wetting time, and in vitro dissolution efficiency) was studied using 32 full factorial designs. In vivo, the diuretic activity was tested for the optimized FUR ODTs by calculating the Lipschitz value using rats as an animal model. The stability of the ODTs loaded with FUR nanoparticles was assessed under accelerated conditions for 6 months. Finally, the ODT formula loaded with FUR NPs showed a rapid onset of action that was significantly faster than untreated drugs. Nanonization and ODT formulation enhances the dissolution rate and bioavailability of FUR. Many factors can be controlled to achieve optimization results, including the formulation and process parameters.

Amiloride versus furosemide for the treatment of edema in patients with nephrotic syndrome: A pilot study (AMILOR).

AIM: In rodent models of nephrotic syndrome (NS), edema formation was prevented by blockade of the epithelial sodium channel ENaC with amiloride. However, apart from case reports, there is no evidence favoring ENaC blockade in patients with NS. METHODS: The monocentric randomized controlled AMILOR study investigated the antiedematous effect of amiloride (starting dose 5 mg/day, max. 15 mg/day) in comparison to standard therapy with the loop diuretic furosemide (40 mg/day, max. 120 mg/day) over 16 days. Overhydration (OH) was measured by bioimpedance spectroscopy (BCM, Fresenius). Depending on the OH response, diuretic dose was adjusted on days 2, 5, 8 and 12, and if necessary, hydrochlorothiazide (HCT) was added from d8 (12.5 mg/day, max. 25 mg/day). The primary endpoint was the decrease in OH on d8. The study was terminated prematurely due to insufficient recruitment and a low statistical power due to a low actual effect size. RESULTS: Median baseline OH was +26.4 (interquartile range 15.5-35.1)% extracellular water (ECW) in the amiloride arm and + 27.9 (24.1-29.4)% ECW in the furosemide arm and decreased by 1.95 (0.80-6.40) and 5.15 (0.90-8.30)% ECW after 8 days, respectively, and by 10.10 (1.30-14.40) and 7.40 (2.80-10.10)% ECW after 16 days, respectively. OH decrease on d8 and d16 was not significantly different between both arms. CONCLUSION: The AMILOR study is the first randomized controlled pilot study suggesting a similar antiedematous effect as furosemide. Further studies are required to better define the role of amiloride in NS (EudraCT 2019-002607-18).

Intralesional combined digoxin and furosemide versus intralesional 5-flurouracil for the treatment of recalcitrant plantar warts: a prospective, randomized study.

There are many therapeutic modalities for plantar warts, however treating it remains challenging. Intralesional injection of 5-fluorouarcil and combined digoxin and furosemide were observed to be effective and safe, however no comparison study between them was done. Our study was conducted to evaluate the efficacy of both therapies in the treatment of plantar warts. 90 adult patients with multiple recalcitrant plantar warts were included in our study. They were randomly allocated to one of three groups; combined digoxin and furosemide, 5-fluorouarcil, or normal saline group. Fortnightly injections were done into all studied warts till complete clearance or up to 5 sessions. Warts were evaluated clinically and dermoscopically. Clinical response was reported in 24 patients (80%) of the combined digoxin and furosemide group with 40% complete response and in 24 patients (80%) of the 5-fluorouarcil group with 33.3% complete response. No statistically significant difference was observed between the two groups concerning efficacy and safety. Intralesional injection of 5-fluorouarcil and combined digoxin and furosemide are nearly equivalent in efficacy and safety for plantar wart treatment. Dermoscopy helps to take the truthful judgment about complete clearance of warts.