Ceftazidime-Avibactam Use in a Case Series of Difficult-to-Treat or Recurrent Infections in Pediatric Patients with Complex Chronic Conditions: Effectiveness and Absence of Resistance Development.

The prevalence of multidrug-resistant Gram-negative infections, particularly carbapenem-resistant strains, has become a significant global health concern. Ceftazidime-avibactam (CZA) has emerged as a promising treatment option. However, data on its efficacy and safety in children are scarce, necessitating further investigation. We conducted a descriptive case series at a tertiary hospital in Spain from February 2019 to January 2022. Pediatric patients (<16 years) treated with CZA for confirmed or suspected multidrug-resistant Gram-negative infections were included. The clinical and microbiological characteristics, treatment approaches, and outcomes were examined. Eighteen children received CZA treatment. All had complex chronic conditions, with the most frequent underlying main diseases being liver transplantation (n = 8) and biliary atresia (n = 4). The predominant type of infection for which they received CZA was intra-abdominal infection caused or suspected to be caused by OXA-48-producing Klebsiella pneumoniae. CZA was generally well tolerated. Within the first month of starting CZA therapy, two patients died, with one case directly linked to the infection's fatal outcome. Some patients needed repeated courses of therapy due to recurrent infections, yet no resistance development was noted. In summary, the use of CZA showed effectiveness and safety, while the lack of resistance development highlights CZA's potential as a primary treatment option against OXA-48-producing infections.

Successful treatment of diplopia using prism correction combined with vision therapy/orthoptics improves health-related quality of life.

Background: To track improvement in diplopia symptoms with strabismus-specific health-related quality of life (HRQOL) questionnaire across a treatment consisting of prism correction followed by vision therapy/orthoptics when prism treatment alone has not succeeded. Methods: Forty-eight participants with diplopia and a mean age of 62.45 were asked to complete an Adult Strabismus-20 (AS-20) questionnaire and a Diplopia Questionnaire (DQ) before and after prism correction. Inclusion criteria were diplopia reported on the DQ as "sometimes", "often" or "always" at reading or straight-ahead distance. The prism correction was classified as successful if the participant reported "never" or "rarely" on the DQ for reading and straight-ahead distance; and unsuccessful if the perceived diplopia worsened or remained the same. For all participants, mean initial AS-20 scores were compared with mean post-prism correction scores, taking into account AS-20 subscales (reading and general functions, and self-perception and interaction). Participants in the failed prism treatment subgroup subsequently underwent a programme of vision therapy wearing their prism correction, the results of which were again determined by participants' responses on the AS-20 questionnaire, completed before and after the vision therapy. Results: Five of the 48 participants dropped out of the study. Prism correction was classified as successful in 22 of 43 participants (51%), and unsuccessful in 21 (49%). Those participants for whom the prism correction was classified as a success showed a statistically significant improvement (p = 0.01) in both reading and general functions. In the failed treatment subgroup, no significant change in AS-20 score was recorded for any of the domains (p = 0.1). After treatment with vision therapy/orthoptics, however, 13 of the 20 participants in the unsuccessful prism correction subgroup (one of them dropped out the study) achieved binocular vision and statistically significant improvement in reading and general functions (p = 0.01). Conclusions: Although effective prism correction of diplopia is correlated with enhanced HRQOL, prism correction alone is frequently not sufficient to achieve this objective. In these cases, vision therapy/orthoptics treatment as a coadjutant to prism correction is shown to improve HRQOL.

Analysis of primary caregivers' knowledge concerning the cariogenic risk associated with the use of pediatric liquid medications / Análisis del conocimiento de los cuidadores principales sobre el riesgo cariogénico implicado en la ingesta de medicamentos líquidos pediátricos

Introduction: Pediatric liquid medications (PLM) are frequently administered to children, yet their usage may contribute to the onset of dental caries. Despite its prevalence, there is a notable scarcity of scientific research regarding caregivers' knowledge of this potential cariogenic risk. Objective: This study aims to assess the knowledge of the main caregivers of children aged 5 to 12 years concerning the cariogenic potential associated with the use of PLM. Materials and Methods: A cross-sectional analytical obser-vational study involving 152 primary caregivers of children aged 5 to 12 was conducted. Data were collected on caregivers' perceptions of the cariogenic risk associated with PLMs and their consumption habits. The study also assessed oral hygiene routines and evaluated the level of information provided by healthcare professionals. Results: Research findings indicated a significant lack of awa-reness among primary caregivers regarding the cariogenic risks of PLMs, with 78.95% being unaware of these risks and 47.37% unaware of the sugars present in such medications. Additionally, a high rate of PLM consumption was observed, with 63% of caregivers using them in the last year. The study underscored a notable absence of guidance from healthcare professionals, as 91.45% of the caregivers stated that they had not received instructions on tooth brushing after the administration of the PLM. Conclusions: The study highlights a significant lack of awa-reness among primary caregivers regarding the cariogenic risks associated with the ingestion of pediatric liquid medications. This deficit in information and preventive measures presents a substantial obstacle to children's oral health. To address this issue, it is crucial for healthcare professionals to offer comprehensive guidance and promote preventive measures.

Introducción: La administración de medicamentos líquidos pediátricos (MLP) es una práctica común en la población infantil y puede estar vinculada al desarrollo de lesiones de caries dental. Sin embargo, la evidencia científica que aborda el conocimiento de los cuidadores acerca de este riesgo cariogénico es escasa. Objetivo: Este estudio busca determinar el conocimiento de los cuidadores principales de niños de 5 a 12 años sobre el potencial cariogénico asociado al consumo de MLP. Materiales y Métodos: Se llevó a cabo un estudio observacional analítico transversal que incluyó a 152 cuidadores principales de niños en el rango de edad de 5 a 12 años. Se recopiló información sobre la percepción de los cuidadores acerca del riesgo cariogénico de los MLP, así como sobre sus patrones de consumo. Además, se registraron las prácticas de higiene oral y se evaluó el nivel de información proporcionado por los profesionales de la salud. Resultado: Los hallazgos de la investigación revelaron que un 78,95% de los cuidadores principales desconocen el riesgo cariogénico asociado al consumo de medicamentos líquidos pediátricos (MLP), y un 47,37% de ellos no eran conscientes de la presencia de azúcares en dichos medicamentos. Además, se observó un elevado índice de consumo de MLP, con un 63% de los cuidadores que los utilizaron en el último año. Se destacó la falta de orientaciones por parte de los profesionales de la salud, ya que, un 91,45% de los tutores afirmaron no haber recibido instrucciones sobre el cepillado dental posterior a la administración de los MLP. Conclusión: Este estudio evidencia un relevante porcentaje de desconocimiento entre los cuidadores principales acerca del riesgo cariogénico asociado a la ingesta de medicamentos líquidos pediátricos. La falta de información y medidas preventivas constituye un desafío significativo para la salud oral de los niños. Es imperativo que los profesionales de la salud proporcionen información detallada y fomenten prácticas de prevención.

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.

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.

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.

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.

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.

[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.

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.

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.

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.