Spirocerca lupi in the stomach of two Andean foxes (Lycalopex culpaeus) from Chile.

The genus Spirocerca includes nematodes that parasitize the stomach and the oesophagus of carnivores, chiefly canids. Herein, we provide new data about the morphological, histopathological, and molecular characterization of Spirocerca sp. in Andean foxes (Lycalopex culpaeus) in Chile. Intact immature worms, identified as Spirocerca sp., were recovered in the lumen of the stomach from two foxes. Histologically, worms morphologically consistent with spirurid nematodes were present within the wall of the stomach and surrounded by nodular areas of inflammation with central necrotic debris. Molecular analysis of the cox1 gene yielded 19 sequences and 5 nucleotide sequence types with 99.95 to 99.98% similarity, being shared between both foxes. Nucleotide similarity ranged from 93.1 (with genotype 2 of S. lupi and S. vulpis) to 95.8% (with genotype 1 of S. lupi), a higher similarity than noted from sequences of S. lupi from an Andean fox from Peru (91.0 to 93.3%). However, the Poisson Tree Processes for species delineation did not support the existence of a new species Spirocerca. Phylogenetic and nucleotide analyses suggest that these specimens belong to a new variant or genotype of S. lupi or to a cryptic species. Whether the presence of the worms in the stomach has to do with genotypic differences in parasites or host or some combination is uncertain. Spirocerca lupi has never been found in Chilean dogs and must be investigated.

Genetics of randomly bred cats support the cradle of cat domestication being in the Near East.

Cat domestication likely initiated as a symbiotic relationship between wildcats (Felis silvestris subspecies) and the peoples of developing agrarian societies in the Fertile Crescent. As humans transitioned from hunter-gatherers to farmers ~12,000 years ago, bold wildcats likely capitalized on increased prey density (i.e., rodents). Humans benefited from the cats' predation on these vermin. To refine the site(s) of cat domestication, over 1000 random-bred cats of primarily Eurasian descent were genotyped for single-nucleotide variants and short tandem repeats. The overall cat population structure suggested a single worldwide population with significant isolation by the distance of peripheral subpopulations. The cat population heterozygosity decreased as genetic distance from the proposed cat progenitor's (F.s. lybica) natural habitat increased. Domestic cat origins are focused in the eastern Mediterranean Basin, spreading to nearby islands, and southernly via the Levantine coast into the Nile Valley. Cat population diversity supports the migration patterns of humans and other symbiotic species.

High seroprevalence of feline morbilliviruses in free-roaming domestic cats in Chile.

Feline morbillivirus infections have gained increased attention due to repeated reports of their association with urinary tract disease in cats. In the present study, 112 serum samples from free-roaming domestic cats in Chile were tested for antibodies against feline morbillivirus genotypes 1 and 2 (FeMV-1 and FeMV-2) using an indirect immunofluorescence assay. In total, 63% of the animals showed antibodies against one or both FeMV genotypes. Antibodies directed exclusively against FeMV-2 were significantly more prevalent in male cats. The correlation of sex and FeMV-2 infection might give insight into potential routes of transmission. We provide, for the first time, serological data on FeMV in Chile.

Hemoplasmas Are Endemic and Cause Asymptomatic Infection in the Endangered Darwin's Fox (Lycalopex fulvipes).

Mycoplasma haemocanis is prevalent in the endangered Darwin's fox (Lycalopex fulvipes) in its main stronghold, Chiloé Island (Chile). The origin of the infection, its dynamics, its presence in other fox populations and the potential consequences for fox health remain unexplored. For 8 years, hemoplasmal DNA was screened and characterized in blood from 82 foxes in Chiloé and two other fox populations and in 250 free-ranging dogs from Chiloé. The prevalence of M. haemocanis in foxes was constant during the study years, and coinfection with "Candidatus Mycoplasma haematoparvum" was confirmed in 30% of the foxes. Both hemoplasma species were detected in the two mainland fox populations and in Chiloé dogs. M. haemocanis was significantly more prevalent and more genetically diverse in foxes than in dogs. Two of the seven M. haemocanis haplotypes identified were shared between these species. Network analyses did not show genetic structure by species (foxes versus dogs), geographic (island versus mainland populations), or temporal (years of study) factors. The probability of infection with M. haemocanis increased with fox age but was not associated with sex, season, or degree of anthropization of individual fox habitats. Some foxes recaptured years apart were infected with the same haplotype in both events, and no hematological alterations were associated with hemoplasma infection, suggesting tolerance to the infection. Altogether, our results indicate that M. haemocanis is enzootic in the Darwin's fox and that intraspecific transmission is predominant. Nevertheless, such a prevalent pathogen in a threatened species represents a concern that must be considered in conservation actions.IMPORTANCEMycoplasma haemocanis is enzootic in Darwin's foxes. There is a higher M. haemocanis genetic diversity and prevalence in foxes than in sympatric dogs, although haplotypes are shared between the two carnivore species. There is an apparent tolerance of Darwin's foxes to Mycoplasma haemocanis.

Molecular survey for cyst-forming coccidia (Toxoplasma gondii, Neospora caninum, Sarcocystis spp.) in Mediterranean periurban micromammals.

Rodents and other micromammals constitute important reservoirs of infectious diseases; their role in the life cycle of apicomplexan parasites such as Toxoplasma gondii, Neospora caninum, and Sarcocystis spp. still needs clarification. In the present study, we analyzed by PCR and Sanger sequencing methods the presence of specific parasite DNA within brain and heart tissues of 313 individuals of five synanthropic small mammal species (Apodemus sylvaticus, Mus spretus, M. musculus, Rattus rattus, and Crocidura russula) collected in Barcelona metropolitan area (NE Spain). In addition, PCR-RFLP and microsatellites were also used as tools for genotypic characterization of T. gondii and N. caninum, respectively. Specific DNA of T. gondii, N. caninum, and Sarcocystis spp. was detected in 0.3% (n = 1), 1.3% (n = 4), and 3.8% (n = 12) of the animals, respectively. No mixed infections were observed. Crocidura russula stood out as the main host for Sarcocystis spp. Toxoplasma gondii-specific DNA detected in a house rat was genetically characterized by PCR-RFLP, presenting type II and III alleles (SAG1 [II], SAG3 [II], GRA6 [II], c22-8 [III], Apico [III]). Also, unsuccessful DNA sequencing and microsatellite typing were attempted in N. caninum-positive samples, which suggested a lack of PCR specificity and open avenues to speculate the host competence of rodents for N. caninum. Likewise, Sarcocystis spp. identity was studied by alignment and phylogenetic analyses of cox1 and 28S rRNA sequences from the 14 positive samples. It resulted in at least three unknown organisms closely similar (95.7-100% cox1-sequence homology) to Sarcocystis pantherophisi from the Eastern rat snake (Pantherophis alleghaniensis) (KU891603), suggesting together with 28S rRNA sequences analyses, three Sarcocystis sp. with a life cycle conformed by rodents as intermediate host (IH) and snakes as definitive hosts (DH) infecting the periurban micromammals surveyed. Prevalence figures found in this first survey carried out in Spain agree with other international studies focused on periurban areas. Further surveys should be conducted in farms and their surroundings in order to unravel the role of wild micromammals in the epidemiology of such protozoan parasites affecting our livestock, and therefore human population.

Molecular investigation of vector-borne parasites in wild micromammals, Barcelona (Spain).

Information about the role of micromammals in the epidemiology of Leishmania infantum and Babesia sp. in southern Europe is scarce. Wild micromammals were captured in natural areas in the Barcelona province (NE Spain) in 2011 and analysed by real-time PCR for the presence of DNA of Piroplasmida (n = 253) and Leishmania infantum (n = 166). The wood mouse (Apodemus sylvaticus) was the most abundant species, but all specimens tested negative for L. infantum, for which two out of 15 (13.3%) white-toothed shrews (Crocidura russula) and one out of 23 (4.3%) Algerian mice (Mus spretus) resulted positive. No individual was positive for Piroplasmida DNA. The role of wild micromammals in the epidemiology of these parasites in the study area seems negligible.

Differences in the ectoparasite fauna between micromammals captured in natural and adjacent residential areas are better explained by sex and season than by type of habitat.

We compared the ectoparasite fauna in 608 micromammals (chiefly 472 wood mice Apodemus sylvaticus, 63 Algerian mice Mus spretus, and 51 greater white-toothed shrews Crocidura russula) captured in natural and adjacent residential areas in spring and autumn during three consecutive years in four areas in periurban Barcelona (NE Spain). We found little support for an association of urbanization with differences in infestation by ectoparasites. Prevalence of Rhipicephalus sp. tick in wood mice and shrews was significantly higher in residential than in natural habitats, and the opposite was found for the flea Ctenophtalmus andorrensis catalanensis in shrews. Marked differences in the prevalence of the flea Leptopsylla taschenbergi amitina in wood mice between seasons were observed in natural but not in residential habitats, probably due to enhanced flea survival probabilities in the latter. However, as a rule, males were more frequently and heavily infested than females, and the prevalence was higher in autumn than in spring. Our results suggest that the ectoparasite fauna of periurban micromammals is shaped more by other factors than by habitat modification. People living in residential areas are at risk of contact with the arthropods borne by non-commensal micromammals and the pathogens transmitted by them.

Using a top predator as a sentinel for environmental contamination with pathogenic bacteria: the Iberian wolf and leptospires.

The Iberian wolf (Canis lupus) is the top predator in the Iberian environments in which it lives, feeding on a wide range of species, thus encountering a wide range of disease agents. Therefore, the wolf can serve as sentinel of environmental contamination with pathogens. We investigated the exposure of free-living wolves to 14 serovars of Leptospira interrogans sensu lato. Kidney samples from 49 wolves collected from 2010-2013 in northwestern Spain were analysed by culture, direct immunofluorescence and polymerase chain reaction. Tissue fluids were analysed for antibodies by a microscopic agglutination test. Ten wolves (observed prevalence: 20%, 95% confidence interval = 11-33%) showed evidence of contact with leptospires, eight through direct detection and nine through serology (7 wolves were positive according to both techniques). Titres below the cut-off level were also detected in seven cases. Serovars confirmed were Canicola (n = 4), Icterohaemorrhagiae (n = 3) and Sejroë, Ballum and Grippotyphosa (n = 1 each), indicating that wolves were infected with serovars for which dogs, rodents and ungulates, are the natural hosts and supporting the utility of the wolf and other large predators as environmental sentinels for pathogens.

Role of wildlife in the epidemiology of Leishmania infantum infection in Europe.

Although dogs are considered the main reservoir of Leishmania infantum infection in endemic areas in Europe, the existence of other wild vertebrate reservoirs has been proposed as a possible cause of the lack of success of control measures. Evidence of L. infantum infection in European wildlife has been reported in carnivores, lagomorphs, and rodents. The red fox (Vulpes vulpes) received most attention, probably due to its taxonomic relationship with the dog and because it is the most abundant wild carnivore in Europe. Foxes and other wild carnivores often displayed high prevalences of infection but their infectiveness to the sandfly vector has never been demonstrated. However, xenodiagnosis demonstrated that black rats (Rattus rattus), are infectious to sandflies. This, together with their relative abundance, high rates of infection, and the fact that infected rats have been found on a Mediterranean island where dogs are not present, makes rats good candidate to be reservoirs of L. infantum. Recently, the Iberian hare (Lepus granatensis) has been recognized as the origin of a leishmaniosis outbreak in humans in Spain and xenodiagnosis showed that this species is also able to infect sandflies. In contrast, a recent survey in cave bats failed to detect infected individuals. In the future, the comparison of parasite isolates from humans, dogs and wildlife, xenodiagnosis studies in wild carnivores, and the study of other vertebrate taxonomic groups will help determine the current role of European wildlife in the epidemiology of leishmaniosis.

Factors associated with the prevalence and pathology of Calodium hepaticum and C. splenaecum in periurban micromammals.

Calodium hepaticum (syn. Capillaria hepatica) and Calodium splenaecum (syn. Capillaria splenaecum) are nematodes that infect the liver and spleen, respectively, of mammals. While the host range, distribution, pathology and zoonotic potential of C. hepaticum are well known, very little is known about C. splenaecum. The observed prevalence of these two parasites, the factors associated with prevalence, and the lesions resulting in the different host species were studied in 408 micromammals captured in two periurban areas of Barcelona (NE Spain) from 2011 to 2013. C. hepaticum was found in 4% of 322 wood mice (Apodemus sylvaticus) (with local prevalence up to 16%) and 1 of 2 Norwegian rats (Rattus norvegicus). C. splenaecum was found in 10 % of 38 greater white-toothed shrew (Crocidura russula) (local prevalence up to 30%). Neither parasite was detected in 29 Algerian mice (Mus spretus) and 17 black rats (Rattus rattus). Prevalence of C. hepaticum was significantly higher in wood mice captured in natural areas (6.4%) than those from residential areas (0%), and infected mice were in better body condition. No differences in prevalence were found among age and sex groups, years and seasons. Lesions of hepatic capillariasis in wood mice consisted mainly of mild to moderate multifocal granulomas around degenerating adult parasites and/or eggs, while lesions seen in a rat consisted of multifocal granulomatous hepatitis and bridging fibrosis extending from the necrotic areas caused by the parasites. Splenic lesions found in shrews due to C. splenaecum, representing the first histological description of this parasite, were single nodules that corresponded to finely encapsulated clusters of eggs with adult parasites.

Absence of Leishmania infantum in cave bats in an endemic area in Spain.

Though dogs have been historically considered the main reservoir of Leishmania infantum, the role of wildlife in its epidemiology is attracting increasing attention. Rodents, wild carnivores and, recently, hares (Lepus spp.) have been proposed as sylvatic reservoirs for this parasite. Bats have never been tested for L. infantum infection in Europe. Nevertheless, bats have a widespread distribution, they live in abundant colonies, and some species inhabit caves, where constant temperatures and humidity provide ideal habitat for the sand fly vector. We tested blood samples from 35 Schreibers' bats (Miniopterus schreibersii), abundant cave bats in NE Spain, which is an enzootic area of leishmaniasis. A PCR-amplifying fragment of the high copy of Leishmania donovani group kDNA minicircles was used. None of the analyzed samples were positive (maximum possible prevalence = 8.20%). Though the susceptibility of this bat to parasitization by L. infantum cannot be ruled out, our survey indicates that this species may not be a relevant sylvatic reservoir of L. infantum in the Mediterranean area. Nevertheless, even if the prevalence of infection in bats is low, such an abundant taxonomic group would still provide a significant maintenance population for the parasite.

Influence of occlusal loading on peri-implant clinical parameters. A pilot study.

OBJECTIVES: To investigate the relation between occlusal loading and peri-implant clinical parameters (probing depth, bleeding on probing, gingival retraction, width of keratinized mucosa, and crevicular fluid volume) in patients with implant-supported complete fixed prostheses in both arches. MATERIAL AND METHODS: This clinical study took place at the University of Valencia (Spain) dental clinic. It included patients attending the clinic for regular check-ups during at least 12 months after rehabilitation of both arches with implant-supported complete fixed ceramo-metallic prostheses. One study implant and one control implant were established for each patient using the T-Scan®III computerized system (Tesco, South Boston, USA). The maxillary implant closest to the point of maximum occlusal loading was taken as the study implant and the farthest (with least loading) as the control. Occlusal forces were registered with the T-Scan® III and then occlusal adjustment was performed to distribute occlusal forces correctly. Peri-implant clinical parameters were analyzed in both implants before and two and twelve months after occlusal adjustment. RESULTS: Before occlusal adjustment, study group implants presented a higher mean volume of crevicular fluid (51.3 ± 7.4 UP) than the control group (25.8 ± 5.5 UP), with statistically significant difference. Two months after occlusal adjustment, there were no significant differences between groups (24.6 ± 3.8 UP and 26 ± 4.5 UP respectively) (p=0.977). After twelve months, no significant differences were found between groups (24.4 ± 11.1 UP and 22.5 ± 8.9 UP respectively) (p=0.323). For the other clinical parameters, no significant differences were identified between study and control implants at any of the study times (p>0.05). CONCLUSIONS: Study group implants receiving higher occlusal loading presented significantly higher volumes of crevicular fluid than control implants. Crevicular fluid volumes were similar in both groups two and twelve months after occlusal adjustment.

Description of Rhipicephalus hibericus sp. nov. (Ixodoidea: Ixodidae), a species of the Rhipicephalus sanguineus group in southwestern Europe.

We describe all the life stages of Rhipicephalus hibericus n. sp., provide the types, and present molecular support for a new species of the Rhipicephalus sanguineus sensu lato group, present in southwestern Europe, that has been historically confused with Rhipicephalus turanicus Pomerantzev, 1940. A new name is proposed for this taxon because it was impossible to ascribe to types of already described species in the group, deposited for more than 100 years in natural history institutions. The males have a dorsum showing deep and coarse punctations (absent in Rhipicephalus sanguineus sensu stricto) and adanal plates with large punctations (absent in R. sanguineus s.s.); the tail of the spiracular plate is as wide as the closest festoon (half the width in R. sanguineus s.s.). Females have large punctations in dorsal fields, a wide spiracular plate, and a "V" shaped genital opening; such a combination of characters cannot be found in other species of the group. Immatures are described from specimens collected on hosts (Rodentia and Eulipotyphla). Both larvae and nymphs are markedly smaller than R. sanguineus s.s. Nymphs display long, backward-projected auriculae; larvae are almost half the size of R. sanguineus s.s. The new species can hybridize with R. sanguineus s.s. in laboratory colonies producing an unfertile F2, laying brown and dry eggs that did not hatch. Phylogenetic analysis of partial coxI gene sequences placed R. hibericus in a well-supported clade with other sequences of R. sanguineus s.l. from Portugal, as a sister clade of R. sanguineus s.s. The new species does not belong to the R. turanicus group of species. Both 12S and 16S partial gene sequences were not as precise in the correct phylogenetic placement of R. hibericus, in part probably due to the existence of erroneously identified sequences in GenBank©. This description, together with the previous reinstatement of Rhipicephalus secundus and Rhipicephalus rutilus, and the description of the neotypes of R. sanguineus s.s. should help researchers to adequately identify their collections. Our findings demonstrate that R. turanicus is absent in southwestern Europe. Old collections should be re-examined to provide the actual range of the new species.

High diversity, novel genotypes, and vertical transmission of hemotropic Mycoplasma in micromammals.

Hemotropic mycoplasmas (hemoplasmas) are emerging zoonotic pathogens. Micromammals have received little attention as hosts for hemoplasmas despite their ubiquitous presence, high population abundances, and close association with humans. A PCR protocol targeting a fragment of the 16 S rRNA gene and direct sequencing in blood samples of 189 adult specimens and 35 fetuses belonging to three species of Eulipotyphla (shrews) and seven species of Rodentia, captured in three ecologically diverse habitats in North-Eastern Spain (Steppe, High Mountain, Mediterranean) yielded and occurrence of 26%, including 36% of 39 shrews and 23% of 150 rodents. Sequencing revealed the presence of 14 nucleotide sequence types (ntST) among the 56 readable sequences. In general, each ntST was associated with a given host species, although in some cases, the same ntST was sequenced in different species (chiefly rodents). Most ntST were closely related to rodent and/or bat hemoplasmas, but one was identical with Mycoplasma haemocanis/haemofelis, and others can be considered novel genotypes. High sequence diversity was detected in rodents, whereas in the white-toothed shrew (Crocidura russula), 9/11 sequences from two distant areas were identical. Phylogenetic and network analyses classified our sequences in different clades including hemoplasmas of rodents, carnivores, bats, and humans. Twelve of the fetuses (34.2%) of 9/12 litters (75.0%) of shrews and rodents were hemoplasma-positive, indicating frequent vertical transmission. Our study contributes to expanding our knowledge about the distribution, diversity, and transmission of hemoplasmas.

Epizootiology and Pathology of Sarcoptic Mange in Two Species of Fox (Lycalopex spp.) in Human-Dominated Landscapes of Central Chile.

Sarcoptic mange caused by Sarcoptes scabiei can have catastrophic consequences for wildlife. We inspected 122 Andean foxes (Lycalopex culpaeus), collected by active (n=66) or passive (n=56) surveillance, and 28 South American gray foxes (Lycalopex griseus; all from passive surveillance) for mange in Chile (2015-19). In Andean foxes, gross lesions of mange were diagnosed in 24% of passively and 9% of actively collected foxes, although observed prevalences might be underestimated. Seroprevalence was 37 and 18%, respectively, indicating that some individuals recovered from infection or were developing the disease. No differences were found between age and sex groups. Comparing data from passive surveillance, occurrence of gross lesions was lower in gray foxes (5%). Body condition was significantly better in Andean foxes without lesions than in diseased foxes, which had significantly lower albumin concentrations than healthy individuals. Among the 12 foxes with gross lesions, four, six and two individuals were categorized as having type I, type II, and type III lesions, respectively, based on clinical severity. Histologic severity correlated with gross lesions and included irregular epidermal hyperplasia with hyperkeratosis, which was marked in type II and III infections. Conventional PCR targeting of the cox1 gene fragment revealed four nucleotide sequence types, showing 99-100% identity among them and between 99% and 100% identity with previously published sequences of S. scabiei. A significant association between the occurrence of mange in foxes and distance to the nearest house was found. We speculate that diseased foxes tended to approach human settlements, perhaps in search of food. Visual inspection of 211 rural dogs from the study area did not reveal gross mange lesions in any animal. Sarcoptic mange is enzootic in the Andean fox in the study area and should be considered in the management of the species.

Radiographic Study of Transcrestal Sinus Floor Elevation Using Osseodensification Technique with Graft Material: A Pilot Study.

This pilot study aimed to evaluate the level of implant success after transcrestal sinus floor elevation (tSFE) using the osseodensification technique (OD) combined with beta-tricalcium phosphate (ß-TCP) by analyzing clinical and radiographic results. Moreover, the increase in bone height was analyzed immediately after surgery, 3 months after, and before loading by taking standardized radiographic measurements. Thirteen patients, four males and nine females, with a mean age of 54.69 ± 5.86 years, requiring the placement of one implant in the upper posterior maxilla, with a residual bone height of <8 mm and a minimum bone width of 5 mm, participated in the study. The bone gain data was obtained using cone-beam computed tomography (CBCT) immediately after surgery and twelve months after the placement. The correlation between initial and final bone height with implant stability was also assessed. The results were analyzed using SPSS 23 software (p < 0.05). The results of the study indicated a 100% implant success rate after a follow-up period of twelve months. Preoperative main bone height was 5.70 ± 0.95 mm. The osseodensification technique allowed a significant increase of 6.65 ± 1.06 mm immediately after surgery. After a twelve-month follow-up, a graft material contraction of 0.90 ± 0.49 mm was observed. No correlation was observed between the bone height at the different times of the study and the primary stability of the implant. Considering the limitations of the size sample of this study, the osseodensification technique used for transcrestal sinus lift with the additional bone graft material (ß-TCP) may provide a predictable elevation of the maxillary sinus floor, allowing simultaneous implant insertion with adequate stability irrespective of bone height limitations.

Blood-Based FTIR Spectroscopy as a Minimally Invasive Diagnostic Method for Colorectal Cancer: A Meta-Analysis.

OBJECTIVE: This meta-analysis aims to pool the results of existing studies to obtain more precise estimates on the diagnostic efficiency of the Fourier transform infrared (FTIR) spectroscopy in detecting CRC using blood-based samples. METHODS: A comprehensive database search identified 4,931 studies that were screened for eligibility. Relevant data were then extracted and collated and analyzed using Meta-DiSc 1.4 to measure the pooled diagnostic accuracy, sensitivity, specificity, likelihood ratio, and diagnostic odds ratio and presented in forest plots. RESULTS: The pooled sensitivity across all six data entries was 86.10% (p = 0.20), and the specificity was 91.2% (p < 0.001). The pooled positive likelihood ratio was 9.84 (p < 0.001), indicating a strongly moderate diagnostic value, while the negative likelihood ratio was 0.16 (0.12), suggesting moderately decreased efficacy of FTIR spectroscopy in ruling out the disease. The pooled AUC was found to be at 0.94 which indicate excellent discriminating potential of FTIR of the method. CONCLUSION: Overall, the study suggests that FTIR spectroscopy has potential as minimally invasive diagnostic method for CRC using plasma samples.

Relationship between clinical congestion and worsening renal function after intravenous initiation of furosemide in patients with acute heart failure.

To investigate if worsening renal function (WRF) appearing in some patients with acute heart failure (AHF) after intravenous furosemide initiation is influenced by severity of congestion. We conducted a retrospective secondary analysis of consecutive patients diagnosed with AHF and prospectively included in 10 Spanish emergency departments (EDs) for whom serum creatinine at ED arrival and after 2-7 days of intravenous furosemide initiation were available. Congestion was clinically evaluated by identification of 7 signs/symptoms and by chest X-ray. The outcome was WRF, defined as a delta-creatinine ≥ 0.3 mg/dL. Risk of WRF according to congestion was estimated in models adjusted by patient baseline characteristics and vitals at ED arrival, and interaction was also investigated. We included 3027 patients (median age 82 years, 56% women), and 657 (21.7%) presented WRF after intravenous furosemide initiation. When signs/symptoms were individually considered, only lower limbs edema was associated with decreased risk of WRF (20.1% vs. 24.8%; OR = 0.76, 95%CI = 0.64-0.91). After adjustment, lower limbs edema persisted inversely associated with WRF (aOR = 0.78, 95%CI = 0.65-0.94), with significant lower risk for patients ≤ 80 years and without chronic kidney disease, functional limitation, and hypoxemia (p for interaction 0.01, 0.04, 0.02 and 0.03, respectively). Neither degree of clinical congestion (number of signs/symptoms of congestion) nor radiological congestion in chest X-ray were related to WRF. Worsening renal function was associated with a higher 1-year all-cause mortality (40.1% vs 34.6%; HR = 1.27, 1.10-1.46; aHR = 1.331, 1.151-1.540). In patients with WRF, liver cirrhosis, chronic treatment with loop diuretics and renin-angiotensin system inhibitors, age (> 80 years), dementia, heart valve disease and NYHA class III-IV were associated with higher mortality. Intravenous furosemide initiation in patients with AHF without lower limbs edema must be cautious, as they are at increasing risk of developing WRF during the next following days, which in turn is associated with a higher 1-year mortality.

Association of intravenous digoxin use in acute heart failure with rapid atrial fibrillation and short-term mortality according to patient age, renal function, and serum potassium.

BACKGROUND: Intravenous digoxin is still used in emergency departments (EDs) to treat patients with acute heart failure (AHF), especially in those with rapid atrial fibrillation. Nonetheless, many emergency physicians are reluctant to use intravenous digoxin in patients with advanced age, impaired renal function, and potassium disturbances due to its potential capacity to increase adverse outcomes. OBJECTIVE: We investigated whether intravenous digoxin used to treat rapid atrial fibrillation in patients with AHF may influence mortality in patients with specific age, estimated glomerular filtration rate (eGFR), and serum potassium classes. DESIGN: A secondary analysis of patients included in in the Spanish EAHFE cohort, which includes patients diagnosed with AHF in the ED. SETTING: 45 Spanish EDs. PARTICIPANTS: Two thousand one hundred ninety-four patients with AHF and rapid atrial fibrillation (heart rate ≥100 bpm) not receiving digoxin at home, divided according to whether they were or were not treated with intravenous digoxin in the ED. OUTCOME: The relationships between age, eGFR, and potassium with 30-day mortality were investigated using restricted cubic spline (RCS) models adjusted for relevant patient and episode variables. The impact of digoxin use on such relationships was assessed by checking interaction. MAIN RESULTS: The median age of the patients was 82 years [interquartile range (IQR) = 76-87], 61.4% were women, 65.2% had previous episodes of atrial fibrillation, and the median heart rate at ED arrival was 120 bpm (IQR = 109-135). Digoxin and no digoxin groups were formed by 864 (39.4%) and 1330 (60.6%) patients, respectively. There were 191 deaths within the 30-day follow-up period (8.9%), with no differences between patients receiving or not receiving digoxin (8.5 vs. 9.1%, P  = 0.636). Although analysis of RCS curves showed that death was associated with advanced age, worse renal function, and hypo- and hyperkalemia, use of intravenous digoxin did not interact with any of these relationships ( P  = 0.156 for age, P  = 0.156 for eGFR; P  = 0.429 for potassium). CONCLUSION: The use of intravenous digoxin in the ED was not associated with significant changes in 30-day mortality, which was confirmed irrespective of patient age or the existence of renal dysfunction or serum potassium disturbances.

Digoxin initiation after an acute heart failure episode and its association with post-discharge outcomes: an international multicenter analysis.

Digoxin is commonly used to treat acute heart failure (AHF), especially in patients with concurrent atrial fibrillation (AF). Nonetheless, there is little consensus about in which patients digoxin should be given, the proper time for digoxin initiation, and whether digoxin initiation is associated with improved outcomes. We investigated factors related to digoxin initiation after an episode of AHF and whether patients receiving digoxin presented better short-term outcomes. We analyzed digoxin-naïve AHF patients from a Spanish and Swiss database, who were dichotomized into cohorts based on their receipt of digoxin treatment at discharge. The relationship between digoxin initiation and 23 additional patient covariates, including chronic treatment, was investigated, as well as its association with 90-day combined adverse events (defined as all-cause death or AHF hospitalization). Of 13,105 patients (10,600/2505 from the Spanish/Swiss cohorts, respectively), the median (interquartile range) age was 83 (74.87) years, and 51% were women. Of these, 484 (3.7%) received digoxin at discharge, which was associated with AF, female sex, left ventricular ejection fraction (LVEF) < 50%, and coming from the Spanish cohort. Parameters inversely associated with receiving digoxin at discharge included some chronic treatments, diabetes mellitus (DM), and chronic kidney disease (CKD). Digoxin initiation was not association with 90-day adverse events, adjusted hazard ratio (aHR) = 0.939 (0.769-1.146), but there was an interaction for CKD, aHR = 1.390 (0.831-2.325) vs. 0.854 (0.682-1.183), p = 0.039, and for cohort pertinence, with higher risk in the Swiss cohort; aHR = 1.405 (0.827-2.386) vs. 0.862 (0.689-1.077), p = 0.046. Digoxin initiation after an AHF episode was more frequent in the Spanish cohort and was associated with certain patient characteristics (AF, female sex, reduced LVEF, no DM, no CKD), but had no effect on 90-day outcomes.