In vitro elicitation of intestinal immune Responses in Teleost Fish: evidence for a type IV hypersensitivity reaction in Rainbow Trout.

In fish the gut immune system has been the subject of few investigations until now. Here, we provide novel morphological and immunological data on the gut isolated from rainbow trout Salmo gairdneri. The pyloric (P) and terminal (T) segments of trout gut, when morphologically examined, evidenced lymphocytes and macrophages (MO) loosely dispersed in the intestinal mucosa and in the lamina propria in the absence of typical Peyer's patches-like structures. Furthermore, incubation of P and T sections with Candida albicans (Ca) and functional analysis of supernatants generated some interesting results. In fact, active supernatants, when compared with controls, exhibited cytokine-like activities attributable to the presence of interferon (IFN)-gamma and migration inhibiting factor (MIF), respectively. In particular, IFN-gamma-like activity gave rise to an enhancement of Ca phagocytosis by MO, whereas MIF inhibited MO migration in agarose. Taken together, these in vitro data suggest that the gut-associated lymphoreticular tissue in fish possesses the appropriate armamentarium to mount a type IV hypersensitivity response when challenged by microbial antigens

Longitudinal serum bicarbonate and mortality risk in older patients with advanced chronic kidney disease: Analyses from the EQUAL cohort

Background. We aimed to explore the relationship between serum bicarbonate (SBC) and mortality in advanced chronic kidney disease (CKD) during three distinct treatment periods: during the pre-kidney replacement therapy (KRT) period, during the transition phase surrounding the start of KRT (transition-CKD) and during KRT. Methods. Using the European QUALity Study on treatment in advanced CKD (EQUAL) cohort, which includes patients aged ≥65 years and estimated glomerular filtration rate (eGFR) ≤20 mL/min/1.73 m2 from six European countries, we explored the association between longitudinal SBC and all-cause mortality in three separate CKD populations: pre-KRT, transition-CKD and in the KRT populations, using multivariable time-dependent Cox regression models. We evaluated effect modification by pre-specified variables on the relationship between SBC and mortality Results. We included 1485 patients with a median follow-up of 2.9 (interquartile range 2.7) years, during which 529 (35.6%) patients died. A U-shaped relationship between SBC levels and all-cause mortality was observed in the pre-KRT population (P = .03). Low cumulative exposure, defined as the area under the SBC trajectory before KRT initiation, was associated with increased mortality risk after transitioning to KRT (P = .01). Similarly, in the KRT population, low SBC levels showed a trend towards increased mortality risk (P = .13). We observed effect modification by subjective global assessment category (P-value for interaction = .02) and KRT (P-value for interaction = .02). Conclusions. A U-shaped relationship describes the association between SBC and mortality in the advanced CKD pre-KRT population, whereas in the KRT population a trend towards an increased mortality risk was observed for low SBC levels

Prescribing patterns in older people with advanced chronic kidney disease towards the end of life

Background. Advancing age and chronic kidney disease (CKD) are risk factors for polypharmacy. Polypharmacy is associated with negative healthcare outcomes. Deprescribing, the systematic rationalization of potentially inappropriate medications, is a proposed way of addressing polypharmacy. The aim of this study was to describe longitudinal prescribing patterns of oral medications in a cohort of older people with advanced CKD in their last years of life. Methods. The European QUALity ( EQUAL) study is a European, prospective cohort study of people >= 65 years with an incident estimated glomerular filtration rate (eGFR) of <= 20 mL/min/1.73 m(2). We analysed a decedent subcohort, using generalized additive models to explore trends in the number and types of prescribed oral medications over the years preceding death. Results. Data from 563 participants were analysed ( comprising 2793 study visits) with a median follow-up time of 2.2 years (interquartile range 1.1-3.8) pre-death. Participants' numbers of prescribed oral medications increased steadily over the years approaching death-7.3 ( 95% confidence interval 6.9-7.7) 5 years pre-death and 8.7 ( 95% confidence interval 8.4-9.0) at death. Over the years pre-death, the proportion of people prescribed (i) proton-pump inhibitors and opiates increased and ( ii) statins, calcium-channel blockers and renin-angiotensin-aldosterone system inhibitors decreased, whilst ( iii) beta-blockers, diuretics and gabapentinoids remained stable. At their final visits pre-death 14.6% and 5.1% were prescribed opiates and gabapentinoids, respectively. Conclusion. Elderly people with advanced CKD experienced persistent and increasing levels of polypharmacy as they approached the end of life. There was evidence of cessation of certain classes of medications, but at a population level this was outweighed by new prescriptions. This work highlights the potential for improved medication review in this setting to reduce the risks associated with polypharmacy. Future work should focus at the individual patient-clinician level to better understand the decision-making process underlying the observed prescribing patterns

Clinical and patient-reported trajectories at end-of-life in older patients with advanced CKD

Background We explore longitudinal trajectories of clinical indicators, patient-reported outcomes, and hospitalizations, in the years preceding death in a population of older patients with advanced chronic kidney disease (CKD). Methods The EQUAL study is a European observational prospective cohort study with an incident eGFR Results We included 661 decedents with a median time to death of 2.0 years (IQR 0.9-3.2). During the years preceding death, eGFR, Subjective Global Assessment score, and blood pressure declined, with accelerations seen at 6 months preceding death. Serum hemoglobin, hematocrit, cholesterol, calcium, albumin, and sodium values declined slowly during follow-up, with accelerations observed between 6 and 12 months preceding death. Physical and mental quality of life declined linearly throughout follow-up. The number of reported symptoms was stable up to 2 years prior to death, with an acceleration observed at 1 year prior to death. The rate of hospitalization was stable at around one hospitalization per person year, increasing exponentially at 6 months preceding death. Conclusions We identified clinically relevant physiological accelerations in patient trajectories that began similar to 6 to 12 months prior to death, which are likely multifactorial in nature, but correlate with a surge in hospitalizations. Further research should focus on how to effectively use this knowledge to inform patient and family expectations, to benefit the planning of (end-of-life) care, and to establish clinical alert systems.Clinical epidemiolog

Do fish thrombocytes play an immunological role? Their cytoenzymatic profiles and function during an accidental piscine candidiasis in aquarium

Fish (F) thrombocytes (THRs) from healthy trouts were studied in terms of cytoenzyme expression. FTHRs were positive to acid periodic of shiff (PAS) and acid phosphatase (ac. phos.) without tartaric acid (-TA) stainings, as well to alkaline phosphatase. However, when compared with autologous macrophages (MOs), they were negative to naphthol cloroacetate esterase (AS-D), alpha-naphthyl acetate esterase (Anae), peroxidase (perox) and control ac. phos. with tartaric acid (+TA) stainings, thus indicating a lack of typical lysosomial enzymes. This evidence supports the notion that FTHRs are not true digesting cells. Quite interestingly, trouts and human MOs were positive for PAS, AS-D, Anae, and perox stainings, thus confirming that cellular cytochemistries are maintained across evolution as their phagocytic functions. Additionally, blood films from trouts, accidentally infected with Candida albicans in aquarium, were morphologically analyzed. Actually, FTHRs interact with erythrocytes, potentiating the formation of rosettes around a central MO. Polymorph nuclear cells and lymphocytes are present in these cellular aggregates, thus suggesting that FTHRs may represent a link between innate and adaptive immunity

A phylogenetic comparison between acute monocytic leukemia cells and monocytes-macrophages in lower vertebrates

In humans, monocytes and macrophages (MO) play a central role in immune regulation, tissue maintenance and pathogen control. In lower vertebrates, a few studies have been conducted on MO like cells. In acute monocytic leukemia monocytic cells, as immature cells restrained in one of the phases of their ontogenesis, would offer the opportunity to rebuild an archaic condition helpful to understand the phylogenesis. Therefore, aim of this work was to characterize in the Rainbow trout (Salmo Gairdneri Richardson) MO and compare them with acute leukemia monocytic cells. In the trout, MO' s morphology is similar to that of mammals. In particular, MO possess an irregular embryoshaped nucleus occupying 2/3 of the cell, while the peripheral cytoplasmic profile is irregular with extroflexed plasmalemma and pseudopods. A morphological transition towards MO is featured by a wavy hyaline classical membrane and an irregular and extroflexed surface.In humans, monocytes and macrophages (MO) play a central role in immune regulation, tissue maintenance and pathogen control. In lower vertebrates, a few studies have been conducted on MO like cells. In acute monocytic leukemia monocytic cells, as immature cells restrained in one of the phases of their ontogenesis, would offer the opportunity to rebuild an archaic condition helpful to understand the phylogenesis. Therefore, aim of this work was to characterize in the Rainbow trout (Salmo Gairdneri Richardson) MO and compare them with acute leukemia monocytic cells.In the trout, MO' s morphology is similar to that of mammals. In particular, MO possess an irregular embryoshaped nucleus occupying 2/3 of the cell, while the peripheral cytoplasmic profile is irregular with extroflexed plasmalemma and pseudopods.A morphological transition towards MO is featured by a wavy hyaline classical membrane and an irregular and extroflexed surface