Dietary tryptophan intervention counteracts stress-induced transcriptional changes in a teleost fish HPI axis during inflammation.

Immune nutrition is currently used to enhance fish health by incorporating functional ingredients into aquafeeds. This study aimed to investigate the connections between tryptophan nutrition and the network that regulates the communication pathways between neuroendocrine and immune systems in European seabass (Dicentrarchus labrax). When tryptophan was supplemented in the diet of unstressed fish, it induced changes in the hypothalamic-pituitary-interrenal axis response to stress. Tryptophan-mediated effects were observed in the expression of anti-inflammatory cytokines and glucocorticoid receptors. Tryptophan supplementation decreased pro-opiomelanocortin b-like levels, that are related with adrenocorticotropic hormone and cortisol secretion. When stressed fish fed a tryptophan-supplemented diet were subjected to an inflammatory stimulus, plasma cortisol levels decreased and the expression of genes involved in the neuroendocrine response was altered. Modulatory effects of tryptophan dietary intervention on molecular patterns seem to be mediated by altered patterns in serotonergic activity.

Dietary Salicornia ramosissima improves the European seabass (Dicentrarchus labrax) inflammatory response against Photobacterium damselae piscicida.

Introduction: Modern fish farming faces challenges in sourcing feed ingredients, most related with their prices, 21 availability, and specifically for plant protein sources, competition for the limited cultivation space for 22 vegetable crops. In that sense, halophytes have the added value of being rich in valuable bioactive compounds and salt tolerant. This study assessed the inclusion of non-food fractions of S. ramosissima in European seabass diets. Methods: Different levels (2.5%, 5%, and 10%) were incorporated into seabass diets, replacing wheat meal (diets ST2.5, ST5, and ST10) or without inclusion (CTRL). Experimental diets were administered to seabass juveniles (8.62 ± 0.63 g) for 34 and 62 days and subsequent inflammatory responses to a heat-inactivated Photobacterium damselae subsp. piscicida (Phdp) were evaluated in a time-course manner (4, 24, 48, and 72 h after the challenge). At each sampling point, seabass haematological profile, plasma immune parameters, and head-kidney immune-related gene expression were evaluated. Results: After both feeding periods, most parameters remained unaltered by S. ramosissima inclusion; nonetheless, seabass fed ST10 showed an upregulation of macrophage colony-stimulating factor 1 receptor 1 (mcsf1r1) and cluster of differentiation 8 (cd8ß) compared with those fed CTRL after 62 days of feeding. Regarding the inflammatory response, seabass fed ST10 showed lower plasma lysozyme levels than their counterparts fed ST2.5 and ST5 at 24 h following injection, while 4 h after the inflammatory stimulus, seabass fed ST10 presented higher numbers of peritoneal leucocytes than fish fed CTRL. Moreover, at 4 h, fish fed ST2.5, ST5, and ST10 showed a higher expression of interleukin 1ß (il1ß), while fish fed ST5 showed higher levels of ornithine decarboxylase (odc) than those fed CTRL. An upregulation of macrophage colony-stimulating factor 1 receptor 1 (mcsf1r1) and glutathione peroxidase (gpx) was also observed at 72 h in fish fed ST10 or ST5 and ST10 compared with CTRL, respectively. Discussion: In conclusion, incorporating up to 10% of the non-food fraction S. ramosissima in feed did not compromise seabass growth or immune status after 62 days, aligning with circular economy principles. However, S. ramosissima inclusion improved the leucocyte response and upregulated key immune-related genes in seabass challenged with an inactivated pathogen.

Shotgun metagenomics and systemic targeted metabolomics highlight indole-3-propionic acid as a protective gut microbial metabolite against influenza infection.

The gut-to-lung axis is critical during respiratory infections, including influenza A virus (IAV) infection. In the present study, we used high-resolution shotgun metagenomics and targeted metabolomic analysis to characterize influenza-associated changes in the composition and metabolism of the mouse gut microbiota. We observed several taxonomic-level changes on day (D)7 post-infection, including a marked reduction in the abundance of members of the Lactobacillaceae and Bifidobacteriaceae families, and an increase in the abundance of Akkermansia muciniphila. On D14, perturbation persisted in some species. Functional scale analysis of metagenomic data revealed transient changes in several metabolic pathways, particularly those leading to the production of short-chain fatty acids (SCFAs), polyamines, and tryptophan metabolites. Quantitative targeted metabolomics analysis of the serum revealed changes in specific classes of gut microbiota metabolites, including SCFAs, trimethylamine, polyamines, and indole-containing tryptophan metabolites. A marked decrease in indole-3-propionic acid (IPA) blood level was observed on D7. Changes in microbiota-associated metabolites correlated with changes in taxon abundance and disease marker levels. In particular, IPA was positively correlated with some Lactobacillaceae and Bifidobacteriaceae species (Limosilactobacillus reuteri, Lactobacillus animalis) and negatively correlated with Bacteroidales bacterium M7, viral load, and inflammation markers. IPA supplementation in diseased animals reduced viral load and lowered local (lung) and systemic inflammation. Treatment of mice with antibiotics targeting IPA-producing bacteria before infection enhanced viral load and lung inflammation, an effect inhibited by IPA supplementation. The results of this integrated metagenomic-metabolomic analysis highlighted IPA as an important contributor to influenza outcomes and a potential biomarker of disease severity.

Enhanced passive safety surveillance of high-dose and standard-dose quadrivalent inactivated split-virion influenza vaccines in Germany and Finland during the 2022/23 influenza season.

Enhanced Passive Safety Surveillance (EPSS) was conducted for quadrivalent inactivated split-virion influenza vaccines (IIV4) in Germany (high dose [HD]) and Finland (standard dose [SD]) for the northern hemisphere (NH) 2022/23 influenza season. The primary objective was to assess adverse events following immunization (AEFI) occurring ≤7 days post-vaccination. In each country, the EPSS was conducted at the beginning of the NH influenza season. Exposure information was documented using vaccination cards (VC), and AEFI were reported via an electronic data collection system or telephone. AEFI were assessed by seriousness and age group (Finland only). The vaccinee reporting rate (RR) was calculated as the number of vaccinees reporting ≥ 1 AEFI divided by the total vaccinees. In Germany, among 1041 vaccinees, there were 31 AEFI (ten vaccinees) during follow-up, including one serious AEFI. Of 16 AEFI (six vaccinees) with reported time of onset, 15 occurred ≤7 days post-vaccination (RR 0.58%, 95% confidence interval [CI] 0.21, 1.25), which was lower than the 2021/22 season (RR 1.88%, 95% CI: 1.10, 3.00). In Finland, among 1001 vaccinees, there were 142 AEFI (51 vaccinees) during follow-up, none of which were serious. Of 133 AEFI (48 vaccinees) with time of onset reported, all occurred ≤7 days post-vaccination (RR 4.80%, 95% CI: 3.56, 6.31), which was similar to the 2021/22 season (RR 4.90%, 95% CI: 3.65, 6.43). The EPSS for HD-IIV4 and for SD-IIV4 in the 2022/23 influenza season did not suggest any clinically relevant changes in safety beyond what is known/expected for IIV4s.

Survival in multiple myeloma and SARS-COV-2 infection through the COVID-19 pandemic: Results from the EPICOVIDEHA registry.

Patients affected by multiple myeloma (MM) have an increased risk of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection and subsequent coronavirus (20)19 disease (COVID-19)-related death. The changing epidemiological and therapeutic scenarios suggest that there has been an improvement in severity and survival of COVID-19 during the different waves of the pandemic in the general population, but this has not been investigated yet in MM patients. Here we analyzed a large cohort of 1221 patients with MM and confirmed SARS-CoV-2 infection observed between February 2020, and August 2022, in the EPICOVIDEHA registry from 132 centers around the world. Median follow-up was 52 days for the entire cohort and 83 days for survivors. Three-hundred and three patients died (24%) and COVID-19 was the primary reason for death of around 89% of them. Overall survival (OS) was significantly higher in vaccinated patients with both stable and active MM versus unvaccinated, while only a trend favoring vaccinated patients was observed in subjects with responsive MM. Vaccinated patients with at least 2 doses showed a better OS than those with one or no vaccine dose. Overall, according to pandemic waves, mortality rate decreased over time from 34% to 10%. In multivariable analysis, age, renal failure, active disease, hospital, and intensive care unit admission, were independently associated with a higher number of deaths, while a neutrophil count above 0.5 × 109 /L was found to be protective. This data suggests that MM patients remain at risk of SARS-CoV-2 infection even in the vaccination era, but their clinical outcome, in terms of OS, has progressively improved throughout the different viral phases of the pandemic.

Natural history and prognostic factors of candidemia in kidney transplant recipients: A retrospective, multinational study.

BACKGROUND: The natural history of candidemia in kidney transplant recipients (KTR) remains poorly understood. This study aimed to evaluate mortality, prognostic factors and overall graft loss after candidemia in KTRs. METHODS: This is a retrospective multicentre study enrolling all KTRs ≥15 years old with candidemia diagnosed at hospitals in Brazil, Spain and Italy from 2010 to 2020. Primary endpoints were mortality rates at 14 and 30 days. Secondary endpoints were prognostic factors of 14-day mortality and overall graft loss. RESULTS: We enrolled 93 KTRs of which 75 were from Brazil. The mean time interval from transplantation to the onset of candidemia was 45.2 ± 61.5 months. 42% of all patients were on haemodialysis, 31.3% had an episode of sepsis and 39% underwent surgery within 30 days before fungemia. European patients were more likely to receive echinocandin (32 vs. 72%, p < .001). 22.7% of Brazilian patients did not receive any antifungal before death. All-cause mortality at 14 days was higher in Brazil (41.3 vs. 11.1%, p = .016). Candida colonisation (OR 6.91 [95% CI: 1.08-44.3], p = .042) and hypotension (OR 4.87 [95% CI: 1.62-14.66], p = .005) were associated with 14-day mortality. Echinocandin treatment had a protective effect (OR 0.19 [95% CI: 0.05-0.73], p = .015). Graft loss at 90 days occurred in 48% of patients (70.7 in Brazil vs. 22.2% in Europe, p < .01). CONCLUSIONS: Candidemia in KTR is usually documented late after engraftment in patients requiring HD, surgical procedures and dysbiosis secondary to antibiotic use. Mortality was higher in Brazil. Echinocandin therapy was associated with improved survival.

Trends in antifungal resistance in Candida from a multicenter study conducted in Madrid (CANDIMAD study): fluconazole-resistant C. parapsilosis spreading has gained traction in 2022.

We previously conducted a multicenter surveillance study on Candida epidemiology and antifungal resistance in Madrid (CANDIMAD study; 2019-2021), detecting an increase in fluconazole-resistant Candida parapsilosis. We here present data on isolates collected in 2022. Furthermore, we report the epidemiology and antifungal resistance trends during the entire period, including an analysis per ward of admission. Candida spp. incident isolates from blood cultures and intra-abdominal samples from patients cared for at 16 hospitals in Madrid, Spain, were tested with the EUCAST E.Def 7.3.2 method against amphotericin B, azoles, micafungin, anidulafungin, and ibrexafungerp and were molecularly characterized. In 2022, we collected 766 Candida sp. isolates (686 patients; blood cultures, 48.8%). Candida albicans was the most common species found, and Candida auris was undetected. No resistance to amphotericin B was found. Overall, resistance to echinocandins was low (0.7%), whereas fluconazole resistance was 12.0%, being higher in blood cultures (16.0%) mainly due to fluconazole-resistant C. parapsilosis clones harboring the Y132F-R398I ERG11p substitutions. Ibrexafungerp showed in vitro activity against the isolates tested. Whereas C. albicans was the dominant species in most hospital wards, we observed increasing C. parapsilosis proportions in blood. During the entire period, echinocandin resistance rates remained steadily low, while fluconazole resistance increased in blood from 6.8% (2019) to 16% (2022), mainly due to fluconazole-resistant C. parapsilosis (2.6% in 2019 to 36.6% in 2022). Up to 7 out of 16 hospitals were affected by fluconazole-resistant C. parapsilosis. In conclusion, rampant clonal spreading of C. parapsilosis fluconazole-resistant genotypes is taking place in Madrid.

Coronary Computed Tomography Angiography Versus Invasive Coronary Angiography in Stable Chest Pain: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The efficacy of coronary computed tomography angiography (CCTA) versus invasive coronary angiography (ICA) among patients with stable chest pain has been studied in several trials with conflicting results. METHODS: We performed a systematic review and meta-analysis comparing CCTA first versus direct ICA among patients with stable chest pain, who were initially referred to ICA. PubMed, EMBASE, and Cochrane Central were searched for randomized controlled trials comparing the 2 strategies. Risk ratios (RRs) and mean differences with 95% CIs were computed for binary and continuous outcomes, respectively. RESULTS: Five randomized controlled trials with a total of 5727 patients were included, of whom 51.1% were referred to CCTA and 22.5% of patients had evidence of ischemia on a prior functional test. In the follow-up ranging from 1 to 3.5 years, 660 of the 2928 patients randomized to CCTA first underwent ICA (23%). Patients who underwent CCTA had lower rates of coronary revascularization (RR, 0.74 [95% CI, 0.66-0.84]; P<0.001) and stroke (RR, 0.50 [95% CI, 0.26-0.98]; P=0.043). Cardiovascular mortality (RR, 0.55 [95% CI, 0.24-1.23]; P=0.146), major adverse cardiovascular events (RR, 0.84 [95% CI, 0.64-1.10]; P=0.198), nonfatal myocardial infarction (RR, 1.09 [95% CI, 0.63-1.88]; P=0.768), and cardiovascular hospitalizations (RR, 0.91 [95% CI, 0.59-1.39]; P=0.669) did not differ significantly between groups. CONCLUSIONS: In patients with stable chest pain referred for ICA, CCTA avoided the need for ICA in 77% of patients otherwise referred for ICA. CCTA was associated with a reduction in the rates of coronary revascularization and stroke compared with direct ICA. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42023383143.

L-methionine supplementation modulates IgM+ B cell responses in rainbow trout.

The interest in dietary amino acids (AAs) as potential immunomodulators has been growing the recent years, since specific AAs are known to regulate key metabolic pathways of the immune response or increase the synthesis of some immune-related proteins. Methionine, tryptophan and lysine are among the ten essential AAs for fish, meaning that they cannot be produced endogenously and must be provided through the diet. To date, although dietary supplementation of fish with some of these AAs has been shown to have positive effects on some innate immune parameters and disease resistance, the effects that these AAs provoke on cells of the adaptive immune system remained unexplored. Hence, in the current study, we have investigated the effects of these three AAs on the functionality of rainbow trout (Oncorhynchus mykiss) IgM+ B cells. For this, splenic leukocytes were isolated from untreated adult rainbow trout and incubated in culture media additionally supplemented with different doses of methionine, tryptophan or lysine in the presence or absence of the model antigen TNP-LPS (2,4,6-trinitrophenyl hapten conjugated to lipopolysaccharide). The survival, IgM secreting capacity and proliferation of IgM+ B cells was then studied. In the case of methionine, the phagocytic capacity of IgM+ B cells was also determined. Our results demonstrate that methionine supplementation significantly increases the proliferative effects provoked by TNP-LPS and also up-regulates the number of cells secreting IgM, whereas tryptophan or lysine have either minor or even negative effects on rainbow trout IgM+ B cells. This increase in the number of IgM-secreting cells in response to methionine surplus was further verified in a feeding experiment, in which the beneficial effects of methionine on the specific response to anal immunization were also confirmed. The results presented demonstrate the beneficial effects of dietary supplementation with methionine on the adaptive immune responses of fish.

Age, successive waves, immunization, and mortality in elderly COVID-19 hematological patients: EPICOVIDEHA findings.

OBJECTIVES: Elderly patients with hematologic malignancies face the highest risk of severe COVID-19 outcomes. The infection's impact on different age groups remains unstudied in detail. METHODS: We analyzed elderly patients (age groups: 65-70, 71-75, 76-80, and >80 years old) with hematologic malignancies included in the EPICOVIDEHA registry between January 2020 and July 2022. Univariable and multivariable Cox regression models were conducted to identify factors influencing death in COVID-19 patients with hematological malignancy. RESULTS: The study included data from 3,603 elderly patients (aged 65 or older) with hematological malignancy, with a majority being male (58.1%) and a significant proportion having comorbidities. The patients were divided into four age groups, and the analysis assessed COVID-19 outcomes, vaccination status, and other variables in relation to age and pandemic waves. The 90-day survival rate for patients with COVID-19 was 71.2%, with significant differences between groups. The pandemic waves had varying impacts, with the first wave affecting patients over 80 years old, the second being more severe in 65-70, and the third being the least severe in all age groups. Factors contributing to 90-day mortality included age, comorbidities, lymphopenia, active malignancy, acute leukemia, less than three vaccine doses, severe COVID-19, and using only corticosteroids as treatment. CONCLUSION: These data underscore the heterogeneity of elderly hematological patients, highlight the different impacts of COVID-19 waves and the pivotal importance of vaccination, and may help in planning future healthcare efforts.

Early Molecular Immune Responses of Turbot (Scophthalmus maximus L.) Following Infection with Aeromonas salmonicida subsp. salmonicida.

Turbot aquaculture production is an important economic activity in several countries around the world; nonetheless, the incidence of diseases, such furunculosis, caused by the etiological agent A. salmonicida subsp. salmonicida, is responsible for important losses to this industry worldwide. Given this perspective, this study aimed to evaluate early immune responses in turbot (S. maximus L.) following infection with A. salmonicida subsp. salmonicida. For this, 72 fish were individually weighed and randomly distributed into 6 tanks in a circulating seawater system. For the bacterial challenge, half of the individuals (3 tanks with 36 individuals) were infected using a peritoneal injection with the bacterial suspension, while the other half of individuals were injected with PBS and kept as a control group. Several factors linked to the innate immune response were studied, including not only haematological (white blood cells, red blood cells, haematocrit, haemoglobin, mean corpuscular volume, mean cell haemoglobin, mean corpuscular haemoglobin concentration, neutrophils, monocytes, lymphocytes, thrombocytes) and oxidative stress parameters, but also the analyses of the expression of 13 key immune-related genes (tnf-α, il-1ß, il-8, pparα-1, acox1, tgf-ß1, nf-kB p65, srebp-1, il-10, c3, cpt1a, pcna, il-22). No significant differences were recorded in blood or innate humoral parameters (lysozyme, anti-protease, peroxidase) at the selected sampling points. There was neither any evidence of significant changes in the activity levels of the oxidative stress indicators (catalase, glutathione S-transferase, lipid peroxidation, superoxide dismutase). In contrast, pro-inflammatory (tnf-α, il-1ß), anti-inflammatory (il-10), and innate immune-related genes (c3) were up-regulated, while another gene linked with the lipid metabolism (acox1) was down-regulated. The results showed new insights about early responses of turbot following infection with A. salmonicida subsp. salmonicida.

Antifungal resistance in Candida spp within the intra-abdominal cavity: study of resistance acquisition in patients with serial isolates.

OBJECTIVES: Antifungal susceptibility testing is mostly conducted on blood-cultured Candida spp isolates. Because the intra-abdominal cavity has been highlighted as a hidden echinocandin-resistant C. glabrata reservoir, we assessed whether testing sequential isolates from a given patient might increase the chances of detecting antifungal resistance. METHODS: Intra-abdominal initial and sequential isolates from the same species from patients included in the CANDIdaemia in MADrid study (January 2019 to June 2022) were studied. We assessed antifungal susceptibility to amphotericin B, azoles, anidulafungin, micafungin, and ibrexafungerp using European Committee on Antimicrobial Susceptibility Testing (EUCAST) methodology and molecularly characterized resistant isolates. RESULTS: We collected 308 isolates (C. albicans [n = 179/308; 58.1%], C. glabrata [n = 101/308; 32.8%], C. tropicalis [n = 17/308; 5.5%], and C. parapsilosis [n = 11/308; 3.6%]) from 112 patients distributed as incident (n = 125/308) and sequential (n = 183/308). Per patient resistance rates of fluconazole (13.4% [15/112] vs. 8% [9/112]); 5.4% proportions difference (95% CI, -2.7% to 13.5%, p 0.09) and echinocandins (8.9% [10/112] vs. 1.8% [2/112]); 7.1% proportions difference (95% CI; 1.2-12.9%; p 0.01) were higher when considering all available isolates than only incident isolates. Resistance was detected in 18 of 112 patients and would have been overlooked in 11 of 18 (61.1%) patients if only incident isolates had been studied. Of the patients who harboured fluconazole or echinocandin-resistant isolates, 14 of 15 and 8 of 10 had received or were receiving fluconazole or echinocandins, respectively. DISCUSSION: Testing sequential Candida isolates from intra-abdominal samples is required to detect antifungal resistance, particularly to echinocandins, in patients whose incident isolates turned out to be susceptible. Furthermore, patients with echinocandin-resistant infections had frequently used echinocandins and had common secondary resistance acquisition.

The Impacts of Plastic Waste from Personal Protective Equipment Used during the COVID-19 Pandemic.

The period from 2019 to 2022 has been defined by the COVID-19 pandemic, resulting in an unprecedented demand for and use of Personal Protective Equipment (PPE). However, the disposal of PPE without considering its environmental impact and proper waste management practices has become a growing concern. The increased demand for PPE during the pandemic and associated waste management practices have been analyzed. Additionally, the discussion around treating these residues and exploring more environmentally friendly alternatives, such as biodegradable or reusable PPE, is crucial. The extensive use of predominantly non-degradable plastics in PPE has led to their accumulation in landfills, with potential consequences for marine environments through the formation of microplastics. Therefore, this article seeks to establish a connection between these issues and the Sustainable Development Goals, emphasizing the importance of efficient management aligned with sustainable development objectives to address these emerging challenges and ensure a more sustainable future.

Bio-Based Pultruded CFRP Laminates: Bond to Concrete and Structural Performance of Full-Scale Strengthened Reinforced Concrete Beams.

This paper presents an experimental study about the use of innovative bio-based pultruded carbon-fiber-reinforced polymer (CFRP) laminates for structural strengthening. The bio-based laminates were produced in the framework of an applied research project (BioLam) using a resin system with 50% (wt.%) bio-based content, obtained from renewable resources. In the first part of the study, their tensile and interlaminar shear properties were characterized and compared with those of conventional oil-based CFRP laminates. In the second part of the study, the bond behavior to concrete of both types of CFRP laminates applied according to the externally bonded reinforcement (EBR) technique was assessed by means of single-lap shear tests performed on CFRP-strengthened concrete blocks; the experimental results obtained from these tests were then used in a numerical procedure to calibrate local bond vs. slip laws for both types of laminates. The final part of this study comprised four-point bending tests on full-scale EBR-CFRP-strengthened reinforced concrete (RC) beams to assess the structural efficacy of the bio-based laminates; these were benchmarked with tests performed on similar RC beams strengthened with conventional CFRP laminates. The results obtained in this study show that the (i) material properties, (ii) the bond behavior to concrete, and (iii) the structural efficacy of the developed bio-based CFRP laminates are comparable to those of their conventional counterparts, confirming their potential to be used in the strengthening of RC structures.

Yeasts from blood cultures in the wake of the COVID-19 pandemic in a tertiary care hospital: Shift in species epidemiology, steady low antifungal resistance and full in vitro ibrexafungerp activity.

Several institutions reported a rise not only in fungemia incidence but also in the number of cases caused by Candida auris or fluconazole-resistant C. parapsilosis during the COVID-19 pandemic. Since the pandemic broke out in early 2020, we studied its impact on fungemia incidence, species epidemiology, potential patient-to-patient transmission, and antifungal resistance in 166 incident yeast isolates collected from January 2020 to December 2022. Isolates were molecularly identified, and their antifungal susceptibilities to amphotericin B, azoles, micafungin, anidulafungin, and ibrexafungerp were studied following the European Committee on Antimicrobial Susceptibility Testing (EUCAST) method, and genotyped. The fungemia incidence (episodes per 1000 admissions) tended to decrease over time (2020 = 1.60, 2021 = 1.36, 2022 = 1.16); P > .05). Species distribution was C. albicans (50.6%, n = 84), C. parapsilosis (18.7%, n = 31), C. glabrata (12.0%, n = 20), C. tropicalis (11.4%, n = 19), C. krusei (3.0%, n = 5), other Candida spp. (1.2%, n = 2), and non-Candida yeasts (3.0%, n = 5). The highest and lowest proportions of C. albicans and C. parapsilosis were detected in 2020. The proportion of isolates between 2020 and 2022 decreased in C. albicans (60.3% vs. 36.7%) and increased in C. parapsilosis (10.3% vs. 28.6%; P < .05) and C. tropicalis (8.8% vs. 16.3%; P > .05). Only three C. albicans intra-ward clusters involving two patients each were detected, and the percentages of patients involved in intra-ward clusters reached 9.8% and 8.0% in 2020 and 2021, respectively, suggesting that clonal spreading was not uncontrolled. Fluconazole resistance (5%) exhibited a decreasing trend (P > .05) over time (2020 = 7.6%; 2021 = 4.2%; and 2022 = 2.1%). Ibrexafungerp showed high in vitro activity.

Fungemia incidence increased during the COVID-19 pandemic in our hospital, however, clonal spreading was not uncontrolled. The proportion of C. parapsilosis and C. tropicalis cases constantly increased. Antifungal resistance remained very low, and fluconazole-resistant C. parapsilosis was undetected.

The Gastrointestinal Tract Is Pinpointed as a Reservoir of Candida albicans, Candida parapsilosis, and Candida tropicalis Genotypes Found in Blood and Intra-Abdominal Samples.

BACKGROUND: Candida spp., as part of the microbiota, can colonise the gastrointestinal tract. We hypothesised that genotyping Candida spp. isolates from the gastrointestinal tract could help spot genotypes able to cause invasive infections. MATERIALS/METHODS: A total of 816 isolates of C. albicans (n = 595), C. parapsilosis (n = 118), and C. tropicalis (n = 103) from rectal swabs (n = 754 patients) were studied. Genotyping was conducted using species-specific microsatellite markers. Rectal swab genotypes were compared with previously studied blood (n = 814) and intra-abdominal (n = 202) genotypes. RESULTS: A total of 36/754 patients had the same Candida spp. isolated from blood cultures, intra-abdominal samples, or both; these patients had candidemia (n = 18), intra-abdominal candidiasis (n = 11), both clinical forms (n = 1), and non-significant isolation (n = 6). Genotypes matching the rectal swab and their blood cultures (84.2%) or their intra-abdominal samples (92.3%) were found in most of the significant patients. We detected 656 genotypes from rectal swabs, 88.4% of which were singletons and 11.6% were clusters. Of these 656 rectal swab genotypes, 94 (14.3%) were also detected in blood cultures and 34 (5.2%) in intra-abdominal samples. Of the rectal swab clusters, 62.7% were previously defined as a widespread genotype. CONCLUSIONS: Our study pinpoints the gastrointestinal tract as a potential reservoir of potentially invasive Candida spp. genotypes.

Skin Cancer and Hydrochlorothiazide: Novel Population-Based Analyses Considering Personal Risk Factors Including Race/Ethnicity.

BACKGROUND: Hydrochlorothiazide, a common antihypertensive, has photosensitive properties, potentially increasing skin cancer risk. We evaluated melanoma and nonmelanoma skin cancer among hydrochlorothiazide users with 3 different cohorts as each allows assessment of different potential cofounders/effect modifiers, including race/ethnicity. METHODS: We built 3 cohorts using IBM MarketScan Research Databases: Commercial and Encounters (>3.5 million individuals, 2010-2018), a subcohort with health risk assessment respondents (415, 330), and Medicaid (509, 767, 2011-2017). Adults (aged 18+ years) entered the respective cohort with a first-filled prescription (cohort entry) for hydrochlorothiazide (the exposure of interest) or angiotensin-converting enzyme (ACE) inhibitors (the active comparator), with ≥12 months of continuous enrollment with medical/pharmacy coverage at baseline. We excluded those who used hydrochlorothiazide/ACE inhibitor (including fixed-dose combination products) 12 months before cohort entry and those with prior skin cancer, HIV, or organ transplant. We compared the risk for hydrochlorothiazide versus ACE inhibitor using multivariate proportional hazards regression. RESULTS: Baseline characteristics were similar, aside from more Black individuals among hydrochlorothiazide users (43.3% [95% CI, 43.0%-43.6%]) than ACE inhibitor users (28.1% [95% CI, 27.9%-28.3%]). The hazard ratio (95% CI) for nonmelanoma skin cancer related to hydrochlorothiazide (versus ACE inhibitor) was 0.96 (0.91-1.00) in the Commercial cohort, 1.01 (0.77-1.32) for the health risk assessment subcohort, and 1.33 (0.77-2.29) for Medicaid. For melanoma, the respective hazard ratios were 1.07 (0.95-1.20), 0.85 (0.43-1.67), and 0.93 (0.51-1.67), respectively. CONCLUSIONS: Our evaluation using 3 different approaches, including adjustment for race/ethnicity, did not establish a clear difference between hydrochlorothiazide and ACE inhibitor in terms of skin cancer risk.

Breakthrough invasive fungal infection among patients with haematologic malignancies: A national, prospective, and multicentre study.

OBJECTIVES: We describe the current epidemiology, causes, and outcomes of breakthrough invasive fungal infections (BtIFI) in patients with haematologic malignancies. METHODS: BtIFI in patients with ≥ 7 days of prior antifungals were prospectively diagnosed (36 months across 13 Spanish hospitals) according to revised EORTC/MSG definitions. RESULTS: 121 episodes of BtIFI were documented, of which 41 (33.9%) were proven; 53 (43.8%), probable; and 27 (22.3%), possible. The most frequent prior antifungals included posaconazole (32.2%), echinocandins (28.9%) and fluconazole (24.8%)-mainly for primary prophylaxis (81%). The most common haematologic malignancy was acute leukaemia (64.5%), and 59 (48.8%) patients had undergone a hematopoietic stem-cell transplantation. Invasive aspergillosis, principally caused by non-fumigatus Aspergillus, was the most frequent BtIFI with 55 (45.5%) episodes recorded, followed by candidemia (23, 19%), mucormycosis (7, 5.8%), other moulds (6, 5%) and other yeasts (5, 4.1%). Azole resistance/non-susceptibility was commonly found. Prior antifungal therapy widely determined BtIFI epidemiology. The most common cause of BtIFI in proven and probable cases was the lack of activity of the prior antifungal (63, 67.0%). At diagnosis, antifungal therapy was mostly changed (90.9%), mainly to liposomal amphotericin-B (48.8%). Overall, 100-day mortality was 47.1%; BtIFI was either the cause or an essential contributing factor to death in 61.4% of cases. CONCLUSIONS: BtIFI are mainly caused by non-fumigatus Aspergillus, non-albicans Candida, Mucorales and other rare species of mould and yeast. Prior antifungals determine the epidemiology of BtIFI. The exceedingly high mortality due to BtIFI warrants an aggressive diagnostic approach and early initiation of broad-spectrum antifungals different than those previously used.