Is it in their eyes? Correlation between microorganisms isolated from bronchial aspirates and conjunctival swabs in a Pediatric Intensive Care Unit / ¿Está en sus ojos? Correlación entre microorganismos aislados de aspirados bronquiales e hisopos conjuntivales en una Unidad de Cuidados Intensivos Pediátricos

Objectives. Our observational, retrospective study aimed to determine the correlation between bacteria isolated from bronchial aspirates of pediatric ICU patients (PICU) with respiratory infections and those obtained from conjunctival swabs of the same patients exhibiting clinical conjunctivitis. Material and methods. Throughout the period from 2015 to 2022, we reviewed all clinically significant bronchial aspirates (≥105 CFU/mL) and positive conjunctival swabs obtained from PICU patients. These records were retrieved from the microbiology database, cross-referencing the data to identify patients who tested positive for both during the same clinical episode. Results. The median age of the patients was 5 months (interquartile range: 1-7). Among the cohort, twenty-one patients exhibited positivity in both bronchial aspirate and conjunctival swab samples, showcasing a microbial match in 85.71% of cases (18 out of 21). The most frequently isolated microorganisms were Haemophilus influenzae (55.6%), followed by Pseudomonas aeruginosa (14.3%), Klebsiella aerogenes (9.5%), and Escherichia coli, Stenotrophomonas maltophilia, and Enterobacter cloacae, each accounting for 4.8% of the isolates. Conclusions. Our study demonstrates a strong concordance between the isolated microorganisms from both samples in patients presenting clear symptoms of clinical conjunctivitis. These findings provide a basis for future prospective studies that may leverage conjunctival swabs as a predictive tool for identifying microorganisms involved in respiratory infections. (AU)

Objetivos. Nuestro estudio observacional y retrospectivo tuvo como objetivo determinar la correlación entre las bacterias aisladas de aspirados bronquiales de pacientes de UCI pediátrica (UCIP) con infecciones respiratorias y las obtenidas de hisopos conjuntivales de los mismos pacientes que presentaban conjuntivitis clínica. Material y métodos. A lo largo del periodo comprendido entre 2015 y 2022, se revisaron todos los aspirados bronquiales clínicamente significativos (≥105 UFC/mL) y los hisopos conjuntivalespositivos obtenidos de pacientes de UCIP. Estos registros se recuperaron de la base de datos de microbiología, cruzando los datos para identificar a los pacientes que dieron positivo en ambos durante el mismo episodio clínico. Resultados. La mediana de edad de los pacientes fue de 5 meses (rango intercuartílico: 1-7). Entre la cohorte, veintiún pacientes presentaron positividad tanto en las muestras de aspirado bronquial como en las de hisopo conjuntival, mostrando una coincidencia microbiana en el 85,71% de los casos (18 de 21). Los microorganismos más frecuentemente aislados fueron Haemophilus influenzae (55,6%), seguido de Pseudomonas aeruginosa (14,3%), Klebsiella aerogenes (9,5%) y Escherichia coli, Stenotrophomonas maltophiliay Enterobacter cloacae, cada uno de los cuales representó el 4,8% de los aislamientos. Conclusiones. Nuestro estudio demuestra una fuerte concordancia entre los microorganismos aislados de ambas muestras en pacientes que presentan síntomas claros de conjuntivitis clínica. Estos hallazgos proporcionan una base para futuros estudios prospectivos que podrían aprovechar los hisopos conjuntivales como herramienta predictiva para identificar microorganismos implicados en infecciones respiratorias. (AU)

Post- versus intra-operative implant for breast cancer interstitial brachytherapy: How to choose?

Purpose: Breast brachytherapy (BB) represents an important radiation therapy modality in modern breast cancer treatments. Currently, BB is mainly used for accelerated partial breast irradiation (APBI), local boost after whole breast radiation therapy (WBRT), and as salvage re-irradiation after second lumpectomy (APBrl). Two multi-catheter interstitial brachytherapy (MIB) techniques can be offered: intra-operative (IOB) and post-operative (POB) brachytherapy. The aim of this article was to summarize current available data on these two different brachytherapy approaches for breast cancer. Material and methods: A literature search was performed, and different experiences published by BB expert teams were analyzed and compared. These two different brachytherapy approaches for breast cancer have also been presented and discussed during meetings of the GEC-ESTRO BCWG. In addition, expert recommendations were defined. Results: A comprehensive description and practical comparison of both the techniques, i.e., IOB and POB, considering the latest available published data were presented. Different technical, logistic, and clinical aspects of both the methods were thoroughly examined and analyzed. This detailed comparison of the two breast brachytherapy techniques was supported by scientific data from extensive experience of experts, facilitating an objective analysis that, to our knowledge, has not been previously published. Conclusions: Based on the comprehensive analysis of both the brachytherapy techniques available, this article serves as a valuable resource to guide breast teams in selecting the optimal BB technique (POB or IOB), considering hospital environment, multi-disciplinary collaboration, and patient logistics.

Very accelerated partial breast irradiation in 1 or 2 days: Late toxicity and early oncological outcome of the GEC-ESTRO VAPBI cohort.

PURPOSE: To analyze late toxicity after very accelerated partial breast irradiation (VAPBI) for low-risk breast cancer. MATERIALS: Methods: In this retrospective, observational, international multicenter study (HDH F20220713143949), patients with low-risk breast cancer underwent lumpectomy + vAPBI (high-dose rate multicatheter interstitial brachytherapy-MIBT). VAPBI was performed with 4(4x6.2 Gy/2d), 3(3x7.45 Gy/2d) or 1 fraction (1x16Gy or 1x18Gy/1d). Primary endpoint was late toxicity. Secondary endpoints were cumulative incidence of breast cancer local relapse (LR) and distant metastatic relapse (DMR) and specific (SS) and overall (OS) survivals. Prognostic factors for late toxicity were analyzed. RESULTS: From 01/2012 to 06/2022, 516 pts with early breast cancer were enrolled. Median follow-up was 44 months [95 %CI 39-46]. Median age was 71 years [40-100]. Median tumor size was 12 mm [1-35]. VAPBI delivered 1, 3 and 4 fractions for 205pts (39.7 %), 167pts (32.4 %) and 144pts (28 %) respectively. 221 late toxicity events were observed in 168pts (32.6 %) (Fibrosis, dyschromia, pain and telangiectasia). Grade 2 and 3 late toxicities were observed in 7.2 and 0.6 % respectively (no G4) with no difference between 1 and ≥ 2 treatment days. CTV > 50 cc (p = 0.007) and V150 > 40 % (p = 0.027) were prognostic factors for G ≥ 2 late toxicity. Four-year cumulative incidence rates of LR and DMR were 2 % [95 %CI 0-3] and 1 % [95 %CI 0-2] respectively. CONCLUSIONS: VAPBI based on 1 or ≥ 2 days of MIBT represents an attractive de-escalation of irradiation approach for low-risk breast cancer. Late toxicity profile appears acceptable while early oncological outcome shows encouraging local control. Longer follow-up is warranted in order to confirm these preliminary results.

Status of head and neck brachytherapy in Spain in 2022

Purpose Brachytherapy (BT) has been used for many years for disease control in tumours of the head and neck area (H&N). It is currently performed with high dose rate (HDR) or pulsed dose rate (PDR), but its use has been reduced due to the implementation of new non-invasive external beam radiotherapy techniques such as intensity modulation (IMRT) and volumetric modulated arc therapy (VMAT) and the improvement of surgical techniques. Methods The Spanish Brachytherapy Group (GEB) has carried out a survey to find out the number of centres in Spain that continue to use BT in H&N and its indications and expectations for the future. Results The results were presented at the XX GEB Consensus Meeting held on October 21, 2022, in Valencia (Spain) and it was confirmed that, although there are fewer and fewer centres that use BT in H&N, there are still units with extensive experience in this technique that should be positioned as referral centres. Conclusion It is necessary to carry out continuous work with other specialities involved, such as H&N surgeons, and other radiation oncologists, to improve the training of residents, both oncologists and medical physicists (AU)

Comparison of dynamic cyclic fatigue resistance of Reciproc® Blue and WaveOne® Gold after sterilization and/or immersion in sodium hypochlorite.

Background: This study aims to compare the cyclic fatigue resistance (CFR) of the Reciproc Blue and WaveOne Gold instruments under a dynamic cyclical fatigue test. Material and Methods: 210 Reciproc Blue "R25" and WaveOne Gold "primary" files were assigned into 7 groups (n =15) for each brand. Groups G: Files were not exposed to NaOCl or sterilization. Groups A and D: files were immersed for 3 minutes in NaOCl 1 and 3 times, respectively. Groups B and E: Files were autoclaved 1 and 3 times, respectively. Groups C and F: files were exposed to both, NaOCl immersion and autoclaving 1 and 3 times, respectively. Subsequently, files underwent a dynamic CFR test. The chemical composition of the files' surface from Group G was analysed by energy-dispersive X-ray spectroscopy (EDS). Cyclic fatigue resistance time was statistically analysed using 1-way and 2-way analyses of variance (ANOVA) and T-test. A p-value ≤0,05 was set to be statistically significant. Results: There was a significantly higher CFR of RB files than WOG in groups A, B, C, D and G (p<0.05). WOG files were superior to RB in group E (p>0.05). There were no statistically significant differences between files in group F (p>0.05). RB files from groups B, C, D, E and F had significantly lower resistance than new ones (Group G) (p<0.05). WaveOne Gold files exposed to 5 % NaOCl immersion in combination with sterilization cycles (Groups C and F) had significantly lower CFR than new ones (p<0.05). Reciproc Blue and WaveOne Gold NiTi alloys differed in atomic wt % of carbon, oxygen, nickel and titanium. Conclusions: The Reciproc Blue files outperformed the WaveOne Gold files in terms of CFR. The Reciproc Blue files were more vulnerable to the cycles of NaOCl immersion or autoclave sterilisation. The combined autoclaving and NaOCl cycles had the most significant impact on the mechanical properties of both files. Key words:Cyclic fatigue, Reciproc blue, Wave one gold, Dynamic test, Simulated channels, Sodium hypochlorite, Sterilization.

Industrial and culinary treatments applied to Piquillo pepper (Capsicum annuum cv. Piquillo) impact positively on (poly)phenols' bioaccessibility and gut microbiota catabolism.

Thermal treatments applied to plant-based foods prior to consumption might influence (poly)phenols' bioaccessibility and the metabolization of these compounds by the gut microbiota. In the present research, the impact of industrial (grilling and canning) and culinary (microwaving and frying) treatments on the bioaccessibility and colonic biotransformations of (poly)phenols from Piquillo pepper (Capsicum annum cv. Piquillo) were evaluated by in vitro gastrointestinal digestion and colonic fermentation models and HPLC-ESI-MS/MS. The application of industrial treatments impacted positively on (poly)phenols' bioaccessibility compared to raw pepper. Microwaving also exerted a positive effect on (poly)phenols' bioaccessibility compared to canning whereas the addition of oil for frying seemed to negatively affect (poly)phenols' release from the food matrix. Throughout the 48 hours of the colonic fermentation process (poly)phenolic compounds were catabolized into different (poly)phenol derivatives whose formation was also positively affected by industrial and culinary treatments. Based on the concentration and time of appearance of these derivatives, catabolic pathways of (poly)phenols from Piquillo pepper were proposed. The major (poly)phenol derivatives identified (3-(3'-hydroxyphenyl)propanoic acid, 4-hydroxy-3-methoxyphenylacetic acid and benzene-1,2-diol) are considered of great interest for the study of their bioactivity and the potential effect on human health.

Status of head and neck brachytherapy in Spain in 2022.

PURPOSE: Brachytherapy (BT) has been used for many years for disease control in tumours of the head and neck area (H&N). It is currently performed with high dose rate (HDR) or pulsed dose rate (PDR), but its use has been reduced due to the implementation of new non-invasive external beam radiotherapy techniques such as intensity modulation (IMRT) and volumetric modulated arc therapy (VMAT) and the improvement of surgical techniques. METHODS: The Spanish Brachytherapy Group (GEB) has carried out a survey to find out the number of centres in Spain that continue to use BT in H&N and its indications and expectations for the future. RESULTS: The results were presented at the XX GEB Consensus Meeting held on October 21, 2022, in Valencia (Spain) and it was confirmed that, although there are fewer and fewer centres that use BT in H&N, there are still units with extensive experience in this technique that should be positioned as referral centres. CONCLUSION: It is necessary to carry out continuous work with other specialities involved, such as H&N surgeons, and other radiation oncologists, to improve the training of residents, both oncologists and medical physicists.

Trasplante autólogo de progenitores hematopoyéticos en paciente con enfermedad de Crohn refractaria / Autologous hematopoietic stem cell transplantation in a patient with refractory Crohn’s disease

La enfermedad de Crohn es una condición crónica para la que en ocasiones no existe tratamiento efectivo, ni médi-co ni quirúrgico. En estos casos, el trasplante autólogo de progenitores hematopoyéticos puede ser una opción tera-péutica con la que restaurar la tolerancia inmunológica del paciente. En algunos casos se conseguirá la remisión de la enfermedad o un descenso en su actividad, haciendo que fármacos que habían fracasado vuelvan a ser efectivos. El perfil de seguridad del procedimiento, unido al hecho de que no es un tratamiento curativo, hace que la selección de los pacientes tenga que ser muy rigurosa.Presentamos nuestra experiencia con el primer pacien-te seleccionado en nuestro centro para trasplante autólogo de progenitores hematopoyéticos: un varón de 27 años con enfermedad de Crohn (A1L3B1p) refractaria a múltiples líneas de tratamiento médico y no candidato a tratamien-to quirúrgico, que dos años tras el trasplante se encuentra asintomático (AU)

Crohn’s disease is a chronic condition for which some-times there is no effective medical or surgical treatment. Autologous hematopoietic stem cell transplantation may be a therapeutic option for these patients to restore immune tolerance. Consequently, this may lead to remission of the disease or decrease its activity, making drugs that have pre-viously failed be effective. Due to the safety profile of the procedure and the fact that it is a non-curative treatment, patient selection must be rigorous.We report our experience with the first patient se-lected in our centre for autologous hematopoietic stem cell transplantation: 27 years old male with Crohn’s dis-ease (A1L3B1p) refractory to multiple lines of medical treatment and not a candidate for surgical treatment. Two years after the transplantation, the patient remains asymptomatic (AU)

Clinical and Microbiological Impact of Implementing a Decision Support Algorithm through Microbiologic Rapid Diagnosis in Critically Ill Patients: An Epidemiological Retrospective Pre-/Post-Intervention Study.

BACKGROUND: Data on the benefits of rapid microbiological testing on antimicrobial consumption (AC) and antimicrobial resistance patterns (ARPs) are scarce. We evaluated the impact of a protocol based on rapid techniques on AC and ARP in intensive care (ICU) patients. METHODS: A retrospective pre- (2018) and post-intervention (2019-2021) study was conducted in ICU patients. A rapid diagnostic algorithm was applied starting in 2019 in patients with a lower respiratory tract infection. The incidence of nosocomial infections, ARPs, and AC as DDDs (defined daily doses) were monitored. RESULTS: A total of 3635 patients were included: 987 in the pre-intervention group and 2648 in the post-intervention group. The median age was 60 years, the sample was 64% male, and the average APACHE II and SOFA scores were 19 points and 3 points. The overall ICU mortality was 17.2% without any differences between the groups. An increase in the number of infections was observed in the post-intervention group (44.5% vs. 17.9%, p < 0.01), especially due to an increase in the incidence of ventilator-associated pneumonia (44.6% vs. 25%, p < 0.001). AC decreased from 128.7 DDD in 2018 to 66.0 DDD in 2021 (rate ratio = 0.51). An increase in Pseudomonas aeruginosa susceptibility of 23% for Piperacillin/tazobactam and 31% for Meropenem was observed. CONCLUSION: The implementation of an algorithm based on rapid microbiological diagnostic techniques allowed for a significant reduction in AC and ARPs without affecting the prognosis of critically ill patients.

Altered Clock Gene Expression in Female APP/PS1 Mice and Aquaporin-Dependent Amyloid Accumulation in the Retina.

Alzheimer's disease (AD), the most prevalent form of dementia, is a neurodegenerative disorder characterized by different pathological symptomatology, including disrupted circadian rhythm. The regulation of circadian rhythm depends on the light information that is projected from the retina to the suprachiasmatic nucleus in the hypothalamus. Studies of AD patients and AD transgenic mice have revealed AD retinal pathology, including amyloid-ß (Aß) accumulation that can directly interfere with the regulation of the circadian cycle. Although the cause of AD pathology is poorly understood, one of the main risk factors for AD is female gender. Here, we found that female APP/PS1 mice at 6- and 12-months old display severe circadian rhythm disturbances and retinal pathological hallmarks, including Aß deposits in retinal layers. Since brain Aß transport is facilitated by aquaporin (AQP)4, the expression of AQPs were also explored in APP/PS1 retina to investigate a potential correlation between retinal Aß deposits and AQPs expression. Important reductions in AQP1, AQP4, and AQP5 were detected in the retinal tissue of these transgenic mice, mainly at 6-months of age. Taken together, our findings suggest that abnormal transport of Aß, mediated by impaired AQPs expression, contributes to the retinal degeneration in the early stages of AD.

Psychometric validation of the Spanish version of the Expanded Prostate Cancer Index Composite-26.

PURPOSE: To assess the validity, reliability, and responsiveness of the Spanish version of the Expanded Prostate cancer Index Composite (EPIC) with 26 items. METHODS: Multicentric longitudinal study of patients diagnosed with localized or locally advanced prostate cancer (any T, any N, M0) treated with active surveillance, surgery, external radiotherapy, or brachytherapy. The EPIC-50 was administered initially to the cohort (n = 324 patients), until it was replaced in November 2019 by the EPIC-26 (n = 543), in both groups before treatment and 12 months after. We assessed confirmatory factor analysis (CFA), reliability with Cronbach's alpha coefficient, criterion validity with the intraclass correlation coefficient (ICC), and responsiveness by testing a priori hypotheses on deterioration effect size (ES). RESULTS: The CFA confirmed the five-domain structure of the EPIC-26 proposed by the original instrument (comparative fit index = 0.95). The agreement between EPIC-50 (gold standard) and EPIC-26 domains was excellent (ICC > 0.90). Cronbach's alpha was > 0.7 in almost all domains, and the floor effect was near zero, although ceiling effect was higher than 50% in urinary incontinence and bowel domains. Hypothesized changes between before and 12 months after treatment were confirmed: ES > 0.8 in both urinary incontinence and sexual domains among patients who underwent surgery; and ES ranging 0.44-0.48 for bowel and sexual domains in patients treated with external radiotherapy. CONCLUSION: The Spanish version of the EPIC-26 has demonstrated adequate metric properties, similar to those of the original version, with acceptable goodness-of-fit indices, good criterion validity, reliability, and responsiveness to detect changes after radical prostatectomy or external radiotherapy.

[Autologous hematopoietic stem cell transplantation in a patient with refractory Crohn's disease].

Crohn's disease is a chronic condition for which sometimes there is no effective medical or surgical treatment. Autologous hematopoietic stem cell transplantation may be a therapeutic option for these patients to restore immune tolerance. Consequently, this may lead to remission of the disease or decrease its activity, making drugs that have previously failed be effective. Due to the safety profile of the procedure and the fact that it is a non-curative treatment, patient selection must be rigorous. We report our experience with the first patient selected in our centre for autologous hematopoietic stem cell transplantation: 27 years old male with Crohn's disease (A1L3B1p) refractory to multiple lines of medical treatment and not a candidate for surgical treatment. Two years after the transplantation, the patient remains asymptomatic.

Spatial patterns associated with the distribution of immature stages of Aedes aegypti in three dengue high-risk municipalities of Southwestern Colombia.

Aedes aegypti mosquitoes are the main vector of human arbovirosis in tropical and subtropical areas. Their adaptation to urban and rural environments generates infestations inside households. Therefore, entomological surveillance associated with spatio-temporal analysis is an innovative approach for vector control and dengue management. Here, our main aim was to inspect immature pupal stages in households belonging to municipalities at high risk of dengue in Cauca, Colombia, by implementing entomological indices and relating how they influence adult mosquitos' density. We provide novel data for the geographical distribution of 3,806 immature pupal stages of Ae. aegypti. We also report entomological indices and spatial characterization. Our results suggest that, for Ae. aegypti species, pupal productivity generates high densities of adult mosquitos in neighbouring households, evidencing seasonal behaviour. Our dataset is essential as it provides an innovative strategy for mitigating vector-borne diseases using vector spatial patterns. It also delineates the association between these vector spatial patterns, entomological indicators, and breeding sites in high-risk neighbourhoods.

Brachytherapy for targeting the immune system in cervical cancer patients.

BACKGROUND: New combinations based on standard therapeutic modalities and immunotherapy require understanding the immunomodulatory properties of traditional treatments. The objective was to evaluate the impact of brachytherapy (BT) on the immune system of cervical cancer and to identify the best modality, High-dose-rate brachytherapy (HDR-BT) vs. Pulsed-dose-rate (PDR-BT), to target it. METHODS: Nineteen patients enrolled in a prospective study received chemoradiation (CRT) and subsequently HDR-BT or PDR-BT. Peripheral blood samples were obtained for immunophenotyping analysis by flow-cytometry before CRT, BT, and two and four weeks after BT. The Friedman one-way ANOVA, Conover post hoc test, and the Wilcoxon signed-rank test were used to compare changes in cell populations at different periods, perform multiple pairwise comparisons and assess differences between treatment groups (PDR and HDR). RESULTS: Natural killer cells (NKs) were the best target for BT. Patients receiving HDR-BT achieved significantly higher values ​​and longer time of the CD56dimCD16 + NK cells with greater cytotoxic capacity than the PDR-BT group, which presented their highest elevation of CD56-CD16 + NK cells. Furthermore, both BT modalities were associated with an increase in myeloid-derived suppressor cells (MDSCs), related to a worse clinical prognosis. However, there was a decrease in the percentage of CD4 + CD25 + Foxp3 + CD45RA + regulatory T cells (Tregs) in patients receiving HDR-BT, although there were no significant differences between BT. CONCLUSIONS: Immune biomarkers are important predictive determinants in cervical cancer. Higher cytotoxic NK cells and a trend toward lower values of Tregs might support the use of HDR-BT to the detriment of PDR-BT and help develop effective combinations with immunotherapy.

Spatial patterns associated with the distribution of immature stages of Aedes aegypti in three high-risk dengue municipalities of Southwestern Colombia / Patrones espaciales asociados a la distribución de estadios inmaduros de Aedes aegypti en tres municipios de alto riesgo para el departamento del Cauca, Colombia

Aedes aegypti mosquitoes are the main vector of human arbovirosis in tropical and subtropical areas.  Its adaptation to urban and rural environments generates infestations inside households. Therefore, entomological surveillance in association with spatio-temporal analysis is an innovative approach to vector control and dengue management. The main aim was to inspect immature pupal stages in households belonging to municipalities at high risk of dengue in Cauca, Colombia by implementing entomological indices and relating how they influence adult mosquito density. Here, we provide novel data for the geographical distribution of 3,806 immature pupal stages of Ae. aegypti. We also report entomological indices and spatial characterization. The results suggest that for Ae. aegypti species, pupal productivity generates high densities of adults in neighbouring households, evidencing seasonal behaviour. This dataset is of great importance as it provides an innovative strategy for vector-borne disease mitigation using vector spatial patterns and their association with entomological indicators and breeding sites in high-risk neighbourhoods.

Los mosquitos Aedes aegypti son el principal vector de las arbovirosis humanas en zonas tropicales y subtropicales. Su adaptación a entornos urbanos y rurales genera infestaciones en el intradomicilio de las viviendas. De aquí que, la vigilancia entomológica en asociación con el análisis espacial y el análisis espacio-temporal sean un enfoque innovador para el control de vectores y la gestión del dengue.El objetivo principal de la investigación fue realizar una comparación de la vigilancia entomológica, mediante el uso de índices cuantitativos de pupas y de adultos en tres municipios de alto riesgo de dengue Patía (El Bordo), Miranda y Piamonte del departamento del Cauca, con el fin de examinar cómo influye la productividad de pupas, entre índices entomológicos, en la densidad de mosquitos adultos y otros patrones espaciales y temporales. Ae. aegypti , sus índices entomológicos y su caracterización espacial. Los resultados sugieren que, para las especies de Ae. aegypti , la productividad de pupas genera altas densidades de adultos en las viviendas vecinas, evidenciando un comportamiento estacional.Estos resultados son de gran importancia ya que proporciona una estrategia innovadora para la mitigación de enfermedades transmitidas por vectores utilizando patrones espaciales de los vectores y su asociación con indicadores entomológicos y lugares de cría en barrios de alto riesgo para la transmisión del dengue.

Adenovirus Infection in Hematopoietic and Solid Organ Paediatric Transplant Recipients: Treatment, Outcomes, and Use of Cidofovir.

BACKGROUND: human adenovirus (hAdV) infection constitutes an important cause of morbidity and mortality in transplant recipients, due to their immune status. Among drugs currently available, cidofovir (CDF) is the most prescribed. METHODS: Retrospective study of hAdV infection in paediatric transplant recipients from a tertiary paediatric centre, describing characteristics, management, and outcomes, and focused on the role of CDF. RESULTS: 49 episodes of infection by hAdV were detected during a four-year period: 38 episodes in patients that received allogeneic hematopoietic stem cell transplantation (77.6%) and 11 in solid organ transplant recipients (22.4%). Twenty-five patients (52.1%) were symptomatic, presenting mainly fever and/or diarrhoea. CDF was prescribed in 24 patients (49%), with modest results. CDF use was associated with the presence of symptoms resulting in lower lymphocyte count, paediatric intensive care unit admission, and high viral load. Other therapeutic measures included administration of intravenous immunoglobulin, reducing immunosuppression, and T-lymphocyte infusion. Despite treatment, 22.9% of patients did not resolve the infection and there were three deaths related to hAdV infection. All-cause mortality was 16.7% (8 episodes) by 30 days, and 32.7% (16 episodes) by 90 days, of which, 3 episodes (3/16, 18.8%) were attributed to hAdV directly. CONCLUSIONS: hAdV infection had high morbidity and mortality in our series. CDF use is controversial, and available therapeutic options are limited. Transplant patients with low lymphocyte count are at higher risk of persistent positive viremias, and short-term survival of these patients was influenced by the resolution of hAdV infection.

Monocyte Activation and Ageing Biomarkers in the Development of Cardiovascular Ischaemic Events or Diabetes in People with HIV.

We investigated whether blood telomere length (TL), epigenetic age acceleration (EAA), and soluble inflammatory monocyte cytokines are associated with cardiovascular events or diabetes (DM) in people living with HIV (PLHIV). This was a case-control study nested in the Spanish HIV/AIDS Cohort (CoRIS). Cases with myocardial infarction, stroke, sudden death, or diabetes after starting antiretroviral therapy were included with the available samples and controls matched for sex, age, tobacco use, pre-ART CD4 cell count, viral load, and sample time-point. TL (T/S ratio) was analysed by quantitative PCR and EAA with DNA methylation changes by next-generation sequencing using the Weidner formula. Conditional logistic regression was used to explore the association with cardiometabolic events. In total, 180 participants (94 cases (22 myocardial infarction/sudden death, 12 strokes, and 60 DM) and 94 controls) were included. Of these, 84% were male, median (IQR) age 46 years (40-56), 53% were current smokers, and 22% had CD4 count ≤ 200 cells/mm3 and a median (IQR) log viral load of 4.52 (3.77-5.09). TL and EAA were similar in the cases and controls. There were no significant associations between TL, EAA, and monocyte cytokines with cardiometabolic events. TL and EAA were mildly negatively correlated with sCD14 (rho = -0.23; p = 0.01) and CCL2/MCP-1 (rho = -0.17; p = 0.02). We found no associations between TL, EAA, and monocyte cytokines with cardiovascular events or diabetes. Further studies are needed to elucidate the clinical value of epigenetic biomarkers and TL in PLHIV.

Differences in glucose metabolic activity in liver metastasis separates two groups of metastatic uveal melanoma patients with different prognosis.

BACKGROUND: Uveal melanoma metastasizes to the liver. We aimed to explore the metabolic activity of liver metastases (LM) as a biomarker for survival. METHODS: We analyzed newly diagnosed patients with metastatic UM (MUM) with LM detected by liver-directed imaging and had undergone a PET/CT at diagnosis. FINDINGS: 51 patients were identified between 2004 and 2019. Median age was 62 years, 41% male and 22% ECOG ≥1. LDH, ALP, and GGT were elevated in 49%, 37%, and 57% of patients. Median LM SUVmax was 8.5 (3-42.2). Same size lesions presented a wide range of metabolic activity. Median OS was 17.3 m (95% CI:10.6-23.9). Patients with SUVmax ≥8.5 had an OS of 9.4 m (95% CI:6.4-12.3), whereas patients with SUVmax <8.5 had an OS of 38.4 m (95% CI:21.4-55.5; p < 0.0001, HR = 2.9). We observed similar results when studying M1a disease separately. Multivariate analysis showed SUVmax as an independent prognostic factor for the whole population and those with M1a disease. INTERPRETATION: Increased metabolic activity of LM seems to be an independent predictor of survival. MUM is a heterogeneous disease and metabolic activity probably reflects a different intrinsic behavior.

LC-MS/MS Analysis Elucidates the Different Effects of Industrial and Culinary Processing on Total and Individual (Poly)phenolic Compounds of Piquillo Pepper (Capsicum annuum cv. Piquillo).

Pepper constitutes an important source of (poly)phenols, mainly flavonoids. Nevertheless, heat treatments applied prior to consumption may have an impact on these antioxidants, and thus may also affect their potential bioactivity. In this study, the effect of industrial and culinary treatments on the total and individual (poly)phenolic content of Piquillo pepper (Capsicum annuum cv. Piquillo) was thoroughly evaluated by high-performance liquid chromatography coupled to tandem mass spectrometry. A total of 40 (poly)phenols were identified and quantified in raw pepper. Flavonoids (10 flavonols, 15 flavones, and 2 flavanones) were the major compounds identified (62.6%). Among the 13 phenolic acids identified in raw samples, cinnamic acids were the most representative. High temperatures applied and subsequent peeling during industrial grilling drastically decreased the total (poly)phenolic content from 2736.34 to 1099.38 µg/g dm (59.8% reduction). In particular, flavonoids showed a higher reduction of 87.2% after grilling compared to nonflavonoids which only decreased by 14%. Moreover, 9 nonflavonoids were generated during grilling, modifying the (poly)phenolic profile. After culinary treatments, specifically frying, (poly)phenols appear to be better released from the food matrix, enhancing their extractability. Overall, industrial and culinary treatments differently affect both the total and individual (poly)phenolic compounds of pepper and, despite the reduction, they might also positively influence their bioaccessibility.