[Acute heart failure (AHF)].

INTRODUCTION: Acute heart failure (AHF) is a frequent cause for emergency consultations, leads to long hospital stays and is characterized by high mortality and rehospitalization rates, with the first months after hospitalization having the highest risk («vulnerable phase¼). The clinical presentation is usually characterized by fluid accumulation. Over the last three decades, few advances have been achieved in the treatment of AHF, as most studies with diuretics or vasodilators failed to show positive effects in terms of mortality and rehospitalization rates. In this context, the treatment of AHF must have an integrative approach, consisting of rapid correction of systemic congestion on the one hand, and specific therapies for the precipitating factors, the underlying cardiac pathology, and non-cardiac comorbidities on the other. Recently, it has been shown that a rapid and intensive up-titration of oral heart failure medical therapy during and immediately after hospitalization can improve the prognosis during the vulnerable phase after AHF. In this article, the principles of optimization and personalization of diuretic therapy and oral heart failure medication during hospitalization and the early outpatient phase after AHF are discussed.

Model systems for regeneration: zebrafish.

Tissue damage can resolve completely through healing and regeneration, or can produce permanent scarring and loss of function. The response to tissue damage varies across tissues and between species. Determining the natural mechanisms behind regeneration in model organisms that regenerate well can help us develop strategies for tissue recovery in species with poor regenerative capacity (such as humans). The zebrafish (Danio rerio) is one of the most accessible vertebrate models to study regeneration. In this Primer, we highlight the tools available to study regeneration in the zebrafish, provide an overview of the mechanisms underlying regeneration in this system and discuss future perspectives for the field.

Prevalence and characteristics of upfront diuretic resistance in acute heart failure: The P-Value-AHF study.

AIMS: Diuretic resistance (i.e., insufficient diuretic and natriuretic response to an appropriate dose of intravenously administered loop diuretic) is a major cause of insufficient decongestion in acute heart failure (AHF). Early assessment of diuretic and natriuretic response already after the first administration of loop diuretic is currently recommended, but few data exist on the prevalence and characteristics of upfront diuretic resistance in AHF. The aim of this sub-study of the P-Value-AHF randomized clinical trial was to investigate the prevalence and characteristics of upfront diuretic resistance in patients presenting with AHF in the emergency department (ED). METHODS: Consecutive patients presenting with a clinical diagnosis of AHF, ≥1 sign of congestion, and NT-proBNP >1000 ng/L between February and June 2024 were prospectively screened. Loop diuretics were administered per protocol: 40 mg furosemide i.v. in diuretic-naïve patients and those on oral torasemide <40 mg, 80 mg furosemide i.v. in patients on oral torasemide ≥40 mg daily. Urine output was measured over the following 2 h and in patients with urine volume <300 mL, urine sodium concentration was additionally measured in a spot sample. Upfront diuretic resistance was defined as urine volume <300 mL in 2 h and urine sodium concentration <70 mmol/L. RESULTS: From a total of 127 screened AHF patients presenting to the ED, 17 subjects were excluded after denial of informed consent and 17 could not be treated according to the protocol due to one or more exclusion criteria. Of the remaining 93 per-protocol-treated patients, 91 showed an adequate diuretic response either in terms of urine volume or urine sodium concentration. Only two of 93 patients (2.2%) met the criteria of upfront diuretic resistance. In a post-hoc analysis, patients with diuretic resistance had higher prevalence of chronic kidney or liver diseases, markedly lower blood pressure and heart rate, markedly higher serum creatinine and potassium levels, and lower serum sodium. Notably, clinical signs of congestion, circulating NT-proBNP, and left-ventricular ejection fraction were similar in both groups. CONCLUSIONS: Upfront diuretic resistance in an unselected population of AHF patients presenting to the ED affects only a minority of patients. These data highlight the importance of a standardized, protocolized approach to decongestive treatment in AHF, which includes the rapid administration of loop diuretics in an adequate dose. Pre-existing chronic kidney disease and high creatinine levels were more prevalent in patients with diuretic resistance.

Differences in mitochondrial function and morphology during cooling and rewarming between hibernator and non-hibernator derived kidney epithelial cells.

Hibernators show superior resistance to ischemia and hypothermia, also outside the hibernation season. Therefore, hibernation is a promising strategy to decrease cellular damage in a variety of fields, such as organ transplantation. Here, we explored the role of mitochondria herein, by comparing epithelial cell lines from a hibernator (hamster kidney cells, HaK) and a non-hibernator (human embryonic kidney cells, HEK293) during cold preservation at 4 °C and rewarming. Cell survival (Neutral Red), ATP and MDA levels, mitochondrial membrane potential (MMP), mitochondrial morphology (using fluorescent probes) and metabolism (seahorse XF) were assessed. Hypothermia induced dispersion of the tubular mitochondrial network, a loss of MMP, increased oxygen radical (MDA) and decreased ATP production in HEK293. In contrast, HaK maintained MMP and ATP production without an increase in oxygen radicals during cooling and rewarming, resulting in superior cell survival compared to HEK293. Further, normothermic HaK showed a dispersed mitochondrial network and higher respiratory and glycolysis capacity compared to HEK293. Disclosing the mechanisms that hibernators use to counteract cell death in hypothermic and ischemic circumstances may help to eventually improve organ preservation in a variety of fields, including organ transplantation.

The efficacy of repellents against Aedes, Anopheles, Culex and Ixodes spp. - a literature review.

BACKGROUND: Travellers are confronted with a variety of vector-borne threats. Is one type of repellent effective against all biting vectors? The aim of this review is to examine the literature, up to December 31st, 2012, regarding repellent efficacy. METHODS: We searched PubMed for relevant papers. Repellents of interest were DEET, Icaridin as well as other piperidine-derived products (SS220), Insect Repellent (IR) 3535 (ethyl-butylacetyl-amino-propionat, EBAAP) and plant-derived products, including Citriodora (para-menthane-3,8-diol). As vectors, we considered the mosquito species Anopheles, Aedes and Culex as well as the tick species Ixodes. We selected only studies evaluating the protective efficacy of repellents on human skin. RESULTS: We reviewed a total of 102 publications. Repellents were evaluated regarding complete protection time or as percentage efficacy [%] in a time interval. We found no standardized study for tick bite prevention. CONCLUSIONS: Regarding Aedes, DEET at concentration of 20% or more, showed the best efficacy providing up to 10 h protection. Citriodora repellency against this mosquito genus was lower compared to the other products. Also between subspecies a difference could be observed: Ae. aegypti proved more difficult to repel than Ae. Albopictus. Fewer studies have been conducted on mosquito species Anopheles and Culex. The repellency profile against Anopheles species was similar for the four principal repellents of interest, providing on average 4-10 h of protection. Culex mosquitoes are easier to repel and all four repellents provided good protection. Few studies have been conducted on the tick species Ixodes. According to our results, the longest protection against Ixodes scapularis was provided by repellents containing IR3535, while DEET and commercial products containing Icaridin or PMD showed a better response than IR3535 against Ixodes ricinus. Many plant-based repellents provide only short duration protection. Adding vanillin 5% to plant-based repellents and to DEET repellents increased the protection by about 2 h.