OBJECTIVE: 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.

The majority of somatosensory DRG neurons express GABAA receptors (GABAAR) and depolarise in response to its activation based on the high intracellular chloride concentration maintained by the Na-K-Cl cotransporter type 1 (NKCC1). The translation of this response to peripheral nerve terminals in people is so far unclear. We show here that GABA (EC50 = 16.67μM) acting via GABAAR produces an influx of extracellular calcium in approximately 20% (336/1720) of isolated mouse DRG neurons. In contrast, upon injection into forearm skin of healthy volunteers GABA (1mM, 100μl) did not induce any overt sensations nor a specific flare response and did not sensitize C-nociceptors to slow depolarizing electrical sinusoidal stimuli. Block of the inward chloride transporter NKCC1 by furosemide (1mg/100μl) did not reduce electrically evoked pain ratings nor did repetitive GABA stimulation in combination with an inhibited NKCC1 driven chloride replenishment by furosemide. Finally, we generated a sustained period of C-fiber firing by iontophoretically delivering codeine or histamine to induce tonic itch. Neither the intensity nor the duration of histamine or codeine itch was affected by prior injection of furosemide. We conclude that although GABA can evoke calcium transients in a proportion of isolated mouse DRG neurons, it does not induce or modify pain or itch ratings in healthy human skin even when chloride gradients are altered by inhibition of the sodium coupled NKCC1 transporter.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: LNCs and PNCs are considered promising nanosysems for improving the diuretic effect of FSM.

OBJECTIVE: 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.

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.

Furosemide is the most used diuretic for volume overload symptoms in patients with heart failure (HF). Recent data suggested that torsemide may be superior to furosemide in this setting. However, whether this translates into better clinical outcomes in this population remains unclear. To assess whether torsemide is superior to furosemide in the setting of HF. We performed a systematic review and meta-analysis of RCTs comparing the efficacy of torsemide versus furosemide in patients with HF. PubMed, Embase, and Web of Science were searched for eligible trials. Outcomes of interest were all-cause hospitalizations, hospitalizations for HF (HHF), hospitalizations for all cardiovascular causes, all-cause mortality, and NYHA class improvement. Echocardiographic parameters were also assessed. We applied a random-effects model to calculate risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) and a 0.05 level of significance. 12 RCTs were included, comprising 4,115 patients. Torsemide significantly reduced HHF (RR 0.60; 95% CI, 0.43-0.83; p=0.002; I2=0%), hospitalization for cardiovascular causes (RR 0.72; 95% CI, 0.60-0.88; p=0.0009; I2=0%), and improved LVEF (MD 4.51%; 95% CI, 2.94 to 6.07; p<0.0001; I2=0%) compared with furosemide. There was no significant difference in all-cause hospitalizations (RR 0.93; 95% CI, 0.86-1.00; p=0.04; I2=0%), all-cause mortality (RR 0.98; 95% CI, 0.87-1.10; p=0.73; I2=0%), NYHA class improvement (RR 1.25; 95% CI, 0.92-1.68; p=0.15; I2=0%), or NYHA class change (MD -0.04; 95% CI, -0.24 to 0.16; p=0.70; I2=15%) between groups. Torsemide significantly reduced hospitalizations for HF and cardiovascular causes, also improving LVEF.
A furosemida é o diurético mais utilizado para o tratamento de sintomas de sobrecarga de volume em pacientes com insuficiência cardíaca. Dados recentes sugerem que a torsemida pode ser superior à furosemida neste contexto. No entanto, ainda não é claro se isso se traduz em melhores resultados clínicos nesta população. Avaliar se a torsemida é superior à furosemida no contexto da insuficiência cardíaca. Realizamos uma revisão sistemática e metanálise de estudos clínicos randomizados (ECRs) comparando a eficácia da torsemida em comparação com a furosemida em pacientes com insuficiência cardíaca. PubMed, Embase e Web of Science foram as bases de dados pesquisadas em busca de estudos elegíveis. Os desfechos de interesse foram internações por todas as causas, internações por insuficiência cardíaca (IIC), internações por todas as causas cardiovasculares, mortalidade por todas as causas, e melhoria de classe da NYHA. Parâmetros ecocardiográficos também foram avaliados. Foi aplicado um modelo de efeitos aleatórios para calcular as razões de risco (RR) e as diferenças médias (DM) com intervalos de confiança (IC) de 95% e nível de significância de 0,05. Foram incluídos 12 ECRs, envolvendo 4.115 pacientes. A torsemida reduziu significativamente a IIC (RR de 0,60; IC de 95%, 0,43-0,83; p=0,002; I2=0%), internação por causas cardiovasculares (RR de 0,72; IC de 95%, 0,60-0,88; p=0,0009; I2=0%), e melhora da fração de ejeção do ventrículo esquerdo (FEVE) (DM de 4,51%; IC de 95%, 2,94 a 6,07; p<0,0001; I2=0%) em comparação com a furosemida. Não houve diferença significativa no número de internações por todas as causas (RR de 0,93; IC de 95%, 0,86-1,00; p=0,04; I2=0%), mortalidade por todas as causas (RR de 0,98; IC de 95%, 0,87-1,10; p=0,73; I2=0%), melhora da classe NYHA (RR de 1,25; IC de 95%, 0,92-1,68; p=0,15; I2=0%), ou mudança de classe NYHA (DM de -0,04; IC de 95%, -0,24 a 0,16; p=0,70; I2=15%) entre os grupos. A torsemida reduziu significativamente as internações por insuficiência cardíaca e causas cardiovasculares, melhorando também a FEVE.

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.

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: 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.
CONCLUSIONS: 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.
BACKGROUND: ClinicalTrials.gov Identifier: NCT05916963 , first received: 22 June 2023. EU Clinical Trials Register EudraCT Number: 2022-502890-40-00.

UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: The subcutaneous furosemide OBI can be safely and effectively used by patients, caregivers, and HCPs, regardless of training.

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.