Effects on Biochemical Parameters and Animal Welfare of Dusky Grouper (Epinephelus marginatus, Lowe 1834) by Feeding CTX Toxic Flesh.

Ciguatera is a foodborne disease caused by ciguatoxins (CTXs), produced by dinoflagellates (genera Gambierdiscus and Fukuyoa), which bioaccumulate in fish through the food web, causing poisoning in humans. Currently, the physiological mechanisms of the species with the highest amount of toxins in their adult stage of life that are capable of causing these poisonings are poorly understood. Dusky grouper (Epinephelus marginatus) is a relevant fishing species and is part of the CTX food chain in the Canary Islands. This study developed an experimental model of dietary exposure featuring adult dusky groupers with two diets of tissue naturally contaminated with CTXs (amberjack and moray eel flesh) with two different potential toxicities; both groups were studied at different stages of exposure (4, 6, 10, 12, and 18 weeks). The results showed that this species did not show changes in its behavior due to the provided feeding, but the changes were recorded in biochemical parameters (mainly lipid and hepatic metabolism) that may respond to liver damage and alterations in the homeostasis of the fish; more research is needed to understand histopathological and cytotoxic changes.

Everolimus Treatment for Chronic Lung Allograft Dysfunction in Lung Transplantation.

Our study aims to evaluate the effect of everolimus treatment on lung function in lung transplant (LT) patients with established chronic lung allograft dysfunction (CLAD). METHODS: This retrospective study included LT patients in two reference LT units who started everolimus therapy to treat CLAD from October 2008 to October 2016. We assessed the variation in the maximum forced expiratory volume in the first second (FEV1) before and after the treatment. RESULTS: Fifty-seven patients were included in this study. The variation in the FEV1 was -102.7 (149.6) mL/month before starting everolimus compared to -44.7 (109.6) mL/month within the first three months, +1.4 (63.5) mL/month until the sixth month, and -7.4 (46.2) mL/month until the twelfth month (p < 0.05). Glomerular filtrate remained unchanged after everolimus treatment [59.1 (17.5) mL/min per 1.73 m2 at baseline and 60.9 (19.6) mL/min per 1.73 m2, 57.7 (20.5) mL/min per 1.73 m2, and 57.3 (17.8) mL/min per 1.73 m2, at 1, 3, and 6 months, respectively] (p > 0.05). Everolimus was withdrawn in 22 (38.6%) patients. The median time to withdrawal was 14.1 (5.5-25.1) months. CONCLUSIONS: This study showed an improvement in FEV1 decline in patients with CLAD treated with everolimus. However, the drug was withdrawn in a high proportion of patients.

Study of histopathology on Arbacia lixula (Arbaciidae: Arbacioida) and Paracentrotus lividus (Parachinidae: Camarodonta) with bald sea urchin disease symptoms in Gran Canaria Island, Spain / Estudio de histopatología en Arbacia lixula (Arbaciidae: Arbacioida) y Paracentrotus lividus (Parachinidae: Camarodonta) con síntomas de la enfermedad del erizo desnudo en la Isla de Gran Canaria, España

Abstract Introduction: Sea urchin diseases have been documented in several locations worldwide, with reported occurrences of bacterial, protozoan, fungal, and algal infections. Objective: This study aimed to investigate pathogen agents in populations of Arbacia lixula and Paracentrotus lividus along the coast of Gran Canaria Island (Central-East Atlantic, Spain). Methods: Sampling was conducted at San Cristobal beach, on the Northeast side of the island, where sea urchins were manually collected from depths of 1-3 m during June, July, and October 2022. Swab samples were taken from the external and internal areas of the lesions and cultured on various media plates. Results: Eight different pathogen agents, including bacteria and fungi, were identified, with Vibrio alginolyticus being the most frequently observed bacteria in all diseased sea urchin samples. Additionally, ciliated protozoans were found within the tests, potentially acting as opportunistic parasites. Conclusions: This research provides a unique perspective on bald sea urchin disease by identifying a significant number of associated pathogens, including Candida, previously unreported in diseased organisms. Furthermore, the study highlights the presence of an inflammatory response in tissues with bacterial colonies, offering crucial insights into understanding this sea urchin disease.

Resumen Introducción: Las enfermedades en los erizos de mar han sido descritas en muchas localidades alrededor del mundo, y se han asociado con la presencia de infecciones por bacterias, protozoarios, hongos y algas. Objetivo: Este estudio tuvo como finalidad investigar sobre los agentes patógenos que afectan a las poblaciones de Arbacia lixula y Paracentrotus lividus a lo largo de la costa de la Isla de Gran Canaria (Atlántico Centro-Oriental, España). Métodos: El muestreo fue llevado a cabo en la playa de San Cristóbal, al noreste de la isla, dónde los organismos fueron capturados entre 1-3 metros de profundidad, durante junio, julio y octubre del año 2022. Se tomaron muestras en la zona interna y externa de la lesión en cada organismo, y se cultivaron en varios medios de cultivo. Resultados: Fueron identificados ocho agentes patógenos diferentes, incluyendo bacterias y hongos, y siendo Vibrio alginolyticus la bacteria más frecuentemente observada en todas las muestras de erizos enfermos. Además, se observaron protozoarios ciliados dentro de los caparazones, actuando potencialmente como parásitos oportunistas. Conclusiones: Esta investigación proporciona una perspectiva única sobre la enfermedad del erizo desnudo al identificar un número significativo de patógenos asociados, incluida Candida, que no se había reportado previamente en organismos enfermos. Además, el estudio destaca la presencia de una respuesta inflamatoria en tejidos con colonias bacterianas, lo que ofrece información crucial para comprender esta enfermedad de los erizos de mar.

Unlocking the Potential of Adequate Bacillus Calmette-Guérin Immunotherapy in Very-high-risk Non-muscle-invasive Bladder Carcinoma: A Multicenter Analysis of Oncological Outcomes and Risk Dynamics.

BACKGROUND: The European Association of Urology (EAU) recommends discussing upfront radical cystectomy for all patients with very high risk (VHR) non-muscle-invasive bladder carcinoma (NMIBC), but the role of bacillus Calmette-Guérin (BCG) treatment remains controversial. OBJECTIVE: To analyze oncological outcomes in VHR NMIBC patients (EAU risk groups) treated with adequate BCG. DESIGN, SETTING, AND PARTICIPANTS: A multi-institutional retrospective study involving patients with VHR NMIBC who received adequate BCG therapy from 2007 to 2020 was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A survival analysis estimated recurrence-free survival (RFS), progression-free survival (PFS), and the cumulative incidence of cancer-specific mortality (CSM) after accounting for other causes of mortality as competing risk events and of the overall mortality (OM). Conditional survival probabilities for 0-4 yr without events were computed. Cox regression assessed the predictors of oncological outcomes. RESULTS AND LIMITATION: A total of 640 patients, with a median 47 (32-67) mo follow-up for event-free individuals, were analyzed. High-grade RFS and PFS at 5 yr were 53% (49-57%) and 78% (74-82%), respectively. The cumulative incidence of CSM and OM at 5 yr was 13% (10-16%) and 16% (13-19%), respectively. Conditional RFS, PFS, overall survival, and cancer-specific survival at 4 yr were 91%, 96%, 87%, and 94%, respectively. Cox regression identified tumor grade (hazard ratio [HR]: 1.54; 1.1-2) and size (HR: 1.3; 1.1-1.7) as RFS predictors. Tumor multiplicity predicted RFS (HR: 1.6; 1.3-2), PFS (HR: 2; 1.2-3.3), and CSM (HR: 2; 1.2-3.2), while age predicted OM (HR: 1.48; 1.1-2). CONCLUSIONS: Patients with VHR NMIBC who receive adequate BCG therapy have a more favorable prognosis than predicted by EAU risk groups, especially among those with a sustained response, in whom continuing maintenance therapy emerges as a viable alternative to radical cystectomy. PATIENT SUMMARY: Our research shows that a sustained response to bacillus Calmette-Guérin in patients can lead to favorable outcomes, serving as a viable alternative to cystectomy for select cases.

First-line Management of Metastatic Urothelial Cancer: Current and Future Perspectives After the EV-302 and CheckMate-901 Studies.

The standard of care for the first-line management of metastatic urothelial carcinoma has been recently challenged, with the combination of pembrolizumab and enfortumab vedotin (P-EV) strongly arising as a practice-changing option from classical platinum-based chemotherapies. With this paradigm shift on the horizon new questions, including the most suitable second line of treatment for these patients, and the role that the molecular characterization of these tumours will have when selecting these therapies will inevitably arise. Furthermore, after the negative results of the Keynote 361 and IMvigor 130 trials, the combination of nivolumab with platinum-based chemotherapy followed by nivolumab maintenance (Nivo GC-Nivo) has also shown positive results when compared with chemotherapy alone. Translational studies at a molecular, cellular, and functional level will be key to better explain these discordant results. In this Current Perspective, we discuss the potential impact of these results in clinical practice and propose specific guidance for prospective translational research.

Equitable Machine Learning for Hypoglycaemia Risk Management.

We developed a machine learning (ML) model for the detection of patients with high risk of hypoglycaemic events during their hospital stay to improve the detection and management of hypoglycaemia. Our model was trained on data from a regional local health care district in Australia. The model was found to have good predictive performance in the general case (AUC 0.837). We conducted subgroup analysis to ensure that the model performed in a way that did not disadvantage population subgroups, in this case based on gender or indigenous status. We found that our specific problem domain assisted us in reducing unwanted bias within the model, because it did not rely on practice patterns or subjective judgements for the outcome measure. With careful analysis for equity there is great potential for ML models to automate the detection of high-risk cohorts and automate mitigation strategies to reduce preventable errors.

Are PARP Inhibitors Ready for Prime Time in Metastatic Prostate Cancer? Maybe Not.

While PARP inhibitors such as rucaparib and olaparib have shown activity in metastatic castration-resistant prostate cancer, they have failed to show a clear improvement in hard outcomes such as overall survival or quality of life. Because of methodological limitations, we suggest caution before implementing these treatments in routine clinical practice; offering them to patients without a BRCA1/2 mutation is probably inappropriate.

Evaluating the Certainty of Evidence in Evidence-based Medicine.

Certainty of evidence (formerly known as quality of evidence) is defined as the extent to which our confidence in an estimate of the effect is correct or our certainty that such estimate supports a particular recommendation for a clinical practice guideline. Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) is a structured and reproducible framework for assigning a level of certainty on a per-outcome basis for evidence derived from randomized and nonrandomized studies. The level of certainty starts as high or low and can be increased or decreased after considering several criteria (eg, risk of bias, inconsistency of results, publication bias, dose-response gradient, large magnitude of effect, among others). Here we describe in brief the GRADE process for summarizing and assigning a certainty rating for evidence. PATIENT SUMMARY: The GRADE framework is a way to work out how much we can trust results from medical research studies. This helps doctors in making informed decisions with their patients.

Leser-Trélat Syndrome, an Underdiagnosed Cutaneous Paraneoplastic Syndrome That Could Aid in Early Detection of Colon Cancer: A Case Report.

Leser-Trélat syndrome, a rare cutaneous paraneoplastic phenomenon, has gained attention for its potential role as an early indicator of underlying internal malignancies. This article presents a comprehensive case study of a 67-year-old male with a history of alcohol and tobacco use, emphasizing the importance of recognizing this syndrome in clinical practice. The sudden onset of seborrheic keratoses on the thorax and back, retrospectively identified as Leser-Trélat syndrome, prompted investigations that led to the early diagnosis of a colon adenocarcinoma. We discuss the pathophysiology, clinical relevance, and controversies surrounding this syndrome, highlighting the need for increased awareness among healthcare professionals. Timely recognition of Leser-Trélat syndrome can significantly impact patient care, leading to improved prognoses for associated neoplasms. This case underscores the importance of comprehensive evaluations and further research to enhance our understanding and management of cutaneous paraneoplastic syndromes.

Evaluation of Quality of Life and Self-reported Complications in Patients With Clean Intermittent Catheterization: An Observational Study.

PURPOSE: This study sought to determine health-related quality of life and self-reported complications associated with clean intermittent catheterization (CIC). DESIGN: Observational, cross-sectional study. SUBJECTS AND SETTING: The target population was patients cared for by the urology department at Hospital 12 de Octubre in Madrid, Spain, undergoing CIC for chronic urinary retention of any etiology (neurogenic bladder dysfunction, neobladder, and other). The sample comprised 50 respondents with a mean age of 49 years; a majority (66%, n = 33) were female. Participants performed an average of 4 CICs. METHODS: All participants completed the ISC-Q (Intermittent Self-Catheterization Questionnaire) and a questionnaire about CIC-associated complications. Data were collected in February 2019. RESULTS: A vast majority of respondents (98%, n = 49) indicated preparation for catheterization was simple, and 76% (n = 38) indicated the catheter was easy to insert. One in 5 (20%, n = 10) considered carrying catheters and supplies inconvenient, though 58% (n = 29) indicated it was easy to dispose of the catheters outside the home. Most respondents (98%, n = 49) indicated they felt self-conscious about their need to self-catheterize, and 16% (n = 8) felt that CIC created limitations when visiting friends and family. The most frequent complication was symptomatic urinary tract infections (UTIs); participants reported an average of 1.7 UTIs in the last year. Additional complications, such as epididymo-orchitis, urethral stenosis, and urethral bleeding, were reported by less than 5% (n = 2) of participants. CONCLUSIONS: Participants managed by CIC for chronic urinary retention of any cause reported acceptable levels of satisfaction with the procedure. The reported incidence of complications was low, except for UTIs.

The definition of ideal training of a urology resident from two different perspectives: trainees vs professors. Is there agreement in their idea of good training?

Introduction: At the end of their residency program, urology trainees should reach the minimum skills required to be able to work by themselves and within a team. To achieve this objective, it is fundamental that the training involves not only surgical activities, but also theoretical, academic, and relational ones. What is the perfect balance between these activities within the ideal urological training? This study aims to evaluate the concordance in different concepts of good urological training between different perspectives (trainees vs professors). Material and methods: Between January and December 2020 the same survey was distributed via email to 967 urology trainees and urology tutors. The survey investigated 5 educational fields: theoretical, clinical, surgical, relational, and simulation. For each field, specific questions investigated the importance of different activities and the training outcomes considered fundamental to be reached by a resident. The questions were evaluated by responders through a Likert 10-point scale. Results: The survey was completed by 155 trainees (58.9%, Group A) and 108 tutors (41.1%, Group B) from 26 different countries. Relative to the tutors, residents assigned statistically significantly lower scores to prostate biopsy (median score 9.11 vs 9.24), robotic simulator training (5.66 vs 5.93), on-call duties with consultants (6.85 vs 7.99), as well as all aspects of relational training (e.g., proper dialogue with colleagues: 7.95 vs 8.88). Conversely, residents assigned statistically significantly higher scores, albeit below sufficiency, to the performance of robotic prostatectomy as a first operator (4.45 vs 4.26). Finally, no discrepancies between residents' and tutors' scores were recorded regarding the remaining items of clinical training (e.g., urodynamics, outpatient clinic, ward duties) and surgical training (e.g., major open, laparoscopic and endoscopic surgical training; all p values >0.05). Conclusions: There was partial concordance between trainees and tutors regarding the activities that should be implemented and the skills that should be achieved during a urological residency. The residents aimed for more surgical involvement, while the tutors and professors, although giving importance to surgical and theoretical training, considered clinical practice as the fundamental basis on which to train future urologists.

ERS International Congress 2022: highlights from the Respiratory Intensive Care Assembly.

Early Career Members of Assembly 2 (Respiratory Intensive Care) attended the 2022 European Respiratory Society (ERS) International Congress in Barcelona, Spain. The conference covered acute and chronic respiratory failure. Sessions of interest to our Assembly members and to those interested in respiratory critical care included the state-of-the-art session on respiratory critical care, the journal session (ERS/Lancet) on acute respiratory distress syndrome (ARDS) phenotyping into precision medicine, and sessions on specificity of coronavirus disease 2019 ARDS and its post-critical care. A symposium on treatment of acute respiratory failure in patients with COPD and innovations in mechanical ventilation either in the intensive care unit or at home were also reported upon. These sessions are summarised in this article.

Ciguatoxin-like toxicity distribution in flesh of amberjack (Seriola spp.) and dusky grouper (Epinephelus marginatus).

Ciguatoxins (CTXs) are marine neurotoxins that cause ciguatera poisoning (CP), mainly through the consumption of fish. The distribution of CTXs in fish is known to be unequal. Studies have shown that viscera accumulate more toxins than muscle, but little has been conducted on toxicity distribution in the flesh, which is the main edible part of fish, and the caudal muscle is also most commonly targeted for the monitoring of CTXs in the Canary Islands. At present, whether this sample is representative of the toxicity of an individual is undisclosed. This study aims to assess the distribution of CTXs in fish, considering different muscle samples, the liver, and gonads. To this end, tissues from four amberjacks (Seriola spp.) and four dusky groupers (Epinephelus marginatus), over 16.5 kg and captured in the Canary Islands, were analyzed by neuroblastoma-2a cell-based assay. Flesh samples were collected from the extraocular region (EM), head (HM), and different areas from the fillet (A-D). In the amberjack, the EM was the most toxic muscle (1.510 CTX1B Eq·g-1), followed by far for the caudal section of the fillet (D) (0.906 CTX1B Eq·g-1). In the dusky grouper flesh samples, D and EM showed the highest toxicity (0.279 and 0.273 CTX1B Eq·g-1). In both species, HM was one of the least toxic samples (0.421 and 0.166 CTX1B Eq·g-1). The liver stood out for its high CTX concentration (3.643 and 2.718 CTX1B Eq·g-1), as were the gonads (1.620 and 0.992 CTX1B Eq·g-1). According to these results, the caudal muscle next to the tail is a reliable part for use in determining the toxicity of fish flesh to guarantee its safe consumption. Additionally, the analysis of the liver and gonads could provide further information on doubtful specimens, and be used for CTX monitoring in areas with an unknown prevalence of ciguatera.

Limited Probiotic Effect of Enterococcus gallinarum L1, Vagococcus fluvialis L21 and Lactobacillus plantarum CLFP3 to Protect Rainbow Trout against Saprolegniosis.

Previous studies have demonstrated that the strains Enterococcus gallinarum L1, Vagococcus fluvialis L21 and Lactobacillus plantarum CLFP3 are probiotics against vibriosis or lactococosis in sea bass or rainbow trout. In this study, the utility of these bacterial strains in the control of saprolegniosis was evaluated. For this purpose, both in vitro inhibition studies and competition for binding sites against Saprolegnia parasitica and in vivo tests with experimentally infected rainbow trout were carried out. In the in vitro tests, the three isolates showed inhibitory activity upon mycelium growth and cyst germination and reduced the adhesion of cysts to cutaneous mucus; however, this effect depended on the number of bacteria used and the incubation time. In the in vivo test, the bacteria were administered orally at 108 CFU g-1 in the feed or at 106 CFU ml-1 in the tank water for 14 days. None of the three bacteria showed protection against S. parasitica infection either through water or feed, and the cumulative mortality reached 100% within 14 days post infection. The obtained results show that the use of an effective probiotic against a certain disease in a host may not be effective against another pathogen or in another host and that the results obtained in vitro may not always predict the effects when used in vivo.

The Association Between Temporal Atrophy and Episodic Memory Is Moderated by Education in a Multi-Center Memory Clinic Sample.

BACKGROUND: Cognitive reserve (CR) is hypothesized to partially explain the discrepancy between Alzheimer's disease related brain pathology and cognitive performance. Educational attainment is often used as a proxy for CR. OBJECTIVE: To examine the association of years of education and the relationship between atrophy in the medial temporal lobe and episodic memory, in a cross-sectional ecological multi-center memory clinic cohort. METHODS: Included patients (n = 702) had undergone memory clinic examination and were diagnosed with subjective cognitive impairment (n = 99), mild cognitive impairment (n = 471), or dementia (n = 132). Total years of education were used as a moderating variable and neuropathology was operationalized as visual ratings of medial temporal lobe atrophy (MTA) on magnetic resonance imaging and computer tomography images. Weighted least squares regression and multiple regression were used to analyze moderation and the effect of education separately by diagnostic group. A composite score of two episodic memory tests constituted the dependent variable. RESULTS: After controlling for age and gender the interaction term between MTA and years of education was significant indicating moderation. In particular, the regression model showed that at low levels of MTA, high education individuals had better episodic memory performance. However, at higher MTA levels, high education individuals had the lowest episodic memory performance. Education had a significant positive effect on episodic memory in SCI and MCI, but not dementia. CONCLUSION: These results extend the findings of education moderating the effect of MTA on cognition to a naturalistic memory clinic setting. Implications of the findings for theories on CR are discussed.