Environmental pollutants as risk factors for autism spectrum disorders: a systematic review and meta-analysis of cohort studies.

BACKGROUND: Autism Spectrum Disorder (ASD) is a lifelong neurodevelopmental condition affecting communication, social interaction, and behavior. Evidence suggests that environmental pollutants are associated with ASD incidence. This review aimed to analyze the effect of environmental pollutants on ASD. METHODS: Systematic review and meta-analysis of cohort studies evaluated the association between exposure to environmental pollutants and ASD. We searched COCHRANE CENTRAL, MEDLINE, CINAHL, LILACS, EMBASE, PsycINFO, Web of Science, SciELO, and gray literature from inception to January 2023. The model used for meta-analysis was inverse variance heterogeneity (IVhet). The effect measures were the beta coefficient (ß) and the relative risk (RR) with their 95% confidence intervals (95% CI). Sensitivity analyses were carried out using an instrument to screen or diagnose autism. RESULTS: A total of 5,780 studies were identified; 27 were included in the systematic review, and 22 were included in the meta-analysis. These studies included 1,289,183 participants and 129 environmental pollutants. Individual meta-analyses found a significant association between nitrogen dioxide RR = 1.20 (95% CI: 1.03 to 1.38; I2: 91%), copper RR = 1.08 (95% CI: 1.03 to 1.13; I2: 0%), mono-3-carboxy propyl phthalate ß = 0.45 (95% CI: 0.20 to 0.70; I2: 0%), monobutyl phthalate ß = 0.43 (95% CI: 0.13 to 0.73; I2: 0%) and polychlorinated biphenyl (PCB) 138 RR = 1.84 (95% CI: 1.14 to 2.96; I2:0%) with ASD. Subgroup meta-analyses found a significant association with carbon monoxide RR = 1.57 (95% CI: 1.25 to 1.97; I2: 0%), nitrogen oxides RR = 1.09 (95% CI: 1.04 to 1.15; I2: 34%) and metals RR = 1.13 (95% CI: 1.01 to 1.27; I2:24%). CONCLUSION: This study found positive associations nitrogen dioxide, copper, mono-3-carboxypropyl phthalate, monobutyl phthalate, and PCB 138, and the development of ASD, likewise, with subgroups of pollutants carbon monoxide, nitrogen oxides, and metals. Therefore, it is important to identify these risk factors in children and adolescents to contribute to ASD and identify prevention strategies effectively.

Advancing Dyslexia Assessment in Children through Computerized Testing.

The acquisition of reading skills is an intricate process that demands the cultivation of various domain-general and domain-specific abilities. Consequently, it is unsurprising that many children grapple with maintaining proficiency at the grade level, particularly when confronted with challenges spanning multiple abilities across both domains, as observed in individuals with reading difficulties. Strikingly, despite reading difficulties being among the most prevalent neurodevelopmental disorders affecting school-aged children, the majority of available diagnostic tools lack a comprehensive framework for assessing the full spectrum of cognitive skills linked to dyslexia, with minimal computerized options. Notably, there are currently limited tools with these features available for Spanish-speaking children. The aim of this study was to delineate the protocol for diagnosing Spanish-speaking children with reading difficulties using the Sicole-R multimedia battery. This tool for elementary grades focuses on evaluating cognitive skills that are associated with dyslexia as prescribed by the scientific literature. Specifically, it concentrates on assessing a range of cognitive abilities that studies have demonstrated to be linked to dyslexia. This focus is based on the observation that individuals with dyslexia typically exhibit deficits in several of the cognitive areas evaluated by this digital tool. The robust internal consistency and multidimensional internal structure of the battery were demonstrated. This multimedia battery has proven to be a fitting tool for diagnosing children with reading difficulties in primary education, offering a comprehensive cognitive profile that is valuable not only for diagnostic purposes but also for tailoring individualized instructional plans.

The effects of intra-accumbal administration of the nicotinic acetylcholine receptor agonist cytisine on the operant oral self-administration of ethanol were prevented by the GABAB receptor agonist baclofen in rats.

RATIONALE: Although the mesocorticolimbic dopamine (DA) system is the main neurochemical substrate that regulates the addictive and reinforcing effects of ethanol (EtOH), other neurotransmitter systems, such as the acetylcholine (Ach) system, modulate DAergic function in the nucleus accumbens (nAcc). Previously, we reported that intra-nAcc administration of the nicotinic Ach receptor agonist cytisine increased oral EtOH self-administration. GABAB receptors in the nAcc are expressed in DAergic terminals, inhibit the regulation of DA release into the nAcc, and could modulate the effects of cytisine on oral EtOH self-administration. The present study assessed the effects of intra-nAcc administration of the GABAB receptor agonist baclofen (BCF) on the impacts of cytisine on oral EtOH self-administration. METHODS: Male Wistar rats were deprived of water for 23.30 h and then trained to press a lever to receive EtOH on an FR3 schedule until a stable response rate of 80 % was achieved. After this training, the rats received an intra-nAcc injection of the nAch receptor agonist cytisine, BCF, and cytisine or 2-hydroxysaclofen, BCF, and cytisine before they were given access to EtOH on an FR3 schedule. RESULTS: Intra-nAcc injections of cytisine increased oral EtOH self-administration; this effect was reduced by BCF, and 2-hydroxysaclofen blocked the effects of BCF. CONCLUSIONS: These findings suggest that the reinforcing effects of EtOH are modulated not only by the DA system but also by other neurotransmitter systems involved in regulating DA release from DAergic terminals.

From Methane to Methanol: Pd-iC-CeO2 Catalysts Engineered for High Selectivity via Mechanochemical Synthesis.

In the pursuit of selective conversion of methane directly to methanol in the liquid-phase, a common challenge is the concurrent formation of undesirable liquid oxygenates or combustion byproducts. However, we demonstrate that monometallic Pd-CeO2 catalysts, modified by carbon, created by a simple mechanochemical synthesis method exhibit 100% selectivity toward methanol at 75 °C, using hydrogen peroxide as oxidizing agent. The solvent free synthesis yields a distinctive Pd-iC-CeO2 interface, where interfacial carbon (iC) modulates metal-oxide interactions and facilitates tandem methane activation and peroxide decomposition, thus resulting in an exclusive methanol selectivity of 100% with a yield of 117 µmol/gcat at 75 °C. Notably, solvent interactions of H2O2 (aq) were found to be critical for methanol selectivity through a density functional theory (DFT)-simulated Eley-Rideal-like mechanism. This mechanism uniquely enables the direct conversion of methane into methanol via a solid-liquid-gas process.

Leaf Gas Film 1 promotes glycerol ester accumulation and formation of a tight root barrier to radial O2 loss in rice.

Rice (Oryza sativa L.) and many other wetland plants form an apoplastic barrier in the outer parts of the roots to restrict radial O2 loss to the rhizosphere during soil flooding. This barrier facilitates longitudinal internal O2 diffusion via gas-filled tissues from shoot to root apices, enabling root growth in anoxic soils. We tested the hypothesis that Leaf Gas Film 1 (LGF1), which influences leaf hydrophobicity in rice, plays a crucial role in tight outer apoplastic barriers formation in rice roots. We examined the roots of a rice mutant (dripping wet leaf 7, drp7) lacking functional LGF1, its wild type, and an LGF1 overexpression line for their capacity to develop outer apoplastic barriers that restrict radial O2 loss. We quantified the chemical composition of the outer part of the root and measured radial O2 diffusion from intact roots. The drp7 mutant exhibited a weak barrier to radial O2 loss compared to the wild type. However, introducing functional LGF1 into the mutant fully restored tight barrier function. The formation of a tight barrier to radial O2 loss was associated with increased glycerol ester levels in exodermal cells, rather than differences in total root suberization or lignification. These results demonstrate that, in addition to its role in leaf hydrophobicity regulation, LGF1 plays an important role in controlling the function of the outer apoplastic barriers in roots. Our study suggests that increased deposition of glycerol esters in the suberized root exodermis establishes a tight barrier to radial O2 loss in rice roots.

Anatomical and physiological responses of roots and rhizomes in Oryza longistaminata to soil water gradients.

BACKGROUND AND AIMS: Roots and rhizomes are critical for the adaptation of clonal plants to soil water gradients. Oryza longistaminata, a rhizomatous wild rice, is of particular interest for perennial rice breeding due to its resilience under abiotic stress conditions. While root responses to soil flooding are well-studied, rhizome responses to water gradients remain underexplored. We hypothesize that physiological integration of Oryza longistaminata mitigates heterogeneous water deficit stress through interconnected rhizomes, and both roots and rhizomes respond to contrasting water conditions. METHODS: We investigated the physiological integration between mother plants and ramets, measuring key photosynthetic parameters (photosynthetic and transpiration rate, and stomatal conductance) using an Infrared Gas Analyzer. Moreover, root and rhizome responses to three water regimes (flooding, well-watered, and water deficit) were examined by measuring radial water loss and apparent permeance to O2, along with histochemical and anatomical characterization. KEY RESULTS: Our experiment highlights the role of physiological integration via interconnected rhizomes in mitigating water deficit stress. Severing rhizome connections from mother plants or ramets exposed to water deficit conditions led to significant decreases in key photosynthetic parameters, underscoring the importance of rhizome connections in bidirectional stress mitigation. Additionally, O. longistaminata rhizomes exhibited constitutive suberized and lignified apoplastic barriers, while such barriers were induced in roots under water stress. Anatomically, both rhizomes and roots respond similarly to water gradients, showing thinner diameters under water deficit conditions and larger diameters under flooding conditions. CONCLUSION: Our findings indicate that physiological integration through interconnected rhizomes helps alleviate water deficit stress when either the mother plant or the ramet is experiencing water deficit, while the counterpart is in control conditions. Moreover, O. longistaminata can adapt to various soil water regimes by regulating anatomical and physiological traits of roots and rhizomes.

Maximizing Nanoscale Downshifting Energy Transfer in a Metallosupramolecular Cr(III)-Er(III) Assembly.

Pseudo-octahedral CrIIIN6 chromophores hold a unique appeal for low-energy sensitization of NIR lanthanide luminescence due to their exceptionally long-lived spin-flip excited states. This allure persists despite the obstacles and complexities involved in integrating both elements into a metallosupramolecular assembly. In this work, we have designed a structurally optimized heteroleptic CrIII building block capable of binding rare earths. Following a complex-as-ligand synthetic strategy, two heterometallic supramolecular assemblies, in which three peripherical CrIII sensitizers coordinated through a molecular wire to a central ErIII or YIII, have been prepared. Upon excitation of the CrIII spin-flip states, the downshifted Er(4I13/2 → 4I15/2) emission at 1550 nm was induced through intramolecular energy transfer. Time-resolved experiments at room temperature reveal a CrIII → ErIII energy transfer of 62-73% efficiencies with rate constants of about 8.5 × 105 s-1 despite the long donor-acceptor distance (circa 14 Å). This efficient directional intermetallic energy transfer can be rationalized using the Dexter formalism, which is promoted by a rigid linear electron-rich alkyne bridge that acts as a molecular wire connecting the CrIII and ErIII ions.

Precision Oncology and Systemic Targeted Therapy in Pseudomyxoma Peritonei.

PURPOSE: Pseudomyxoma peritonei (PMP) is a rare and poorly understood malignant condition characterized by the accumulation of intra-abdominal mucin produced from peritoneal metastases. Currently, cytoreductive surgery remains the mainstay of treatment but disease recurrence and death after relapse frequently occur in patients with PMP. New therapeutic strategies are therefore urgently needed for these patients. EXPERIMENTAL DESIGN: A total of 120 PMP samples from 50 patients were processed to generate a collection of 50 patient-derived organoid (PDO) and xenograft (PDX) models. Whole exome sequencing, immunohistochemistry analyses, and in vitro and in vivo drug efficacy studies were performed. RESULTS: In this study, we have generated a collection of PMP preclinical models and identified druggable targets, including BRAFV600E, KRASG12C, and KRASG12D, that could also be detected in intra-abdominal mucin biopsies of patients with PMP using droplet digital PCR. Preclinical models preserved the histopathological markers from the original patient sample. The BRAFV600E inhibitor encorafenib reduced cell viability of BRAFV600E PMP-PDO models. Proof-of-concept in vivo experiments showed that a systemic treatment with encorafenib significantly reduced tumor growth and prolonged survival in subcutaneous and orthotopic BRAFV600E-PMP-PDX mouse models. CONCLUSIONS: Our study demonstrates for the first time that systemic targeted therapies can effectively control PMP tumors. BRAF signaling pathway inhibition represents a new therapeutic opportunity for patients with BRAFV600E PMP who have a poor prognosis. Importantly, our present data and collection of preclinical models pave the way for evaluating the efficacy of other systemic targeted therapies toward extending the promise of precision oncology to patients with PMP.

Taming 2,2'-biimidazole ligands in trivalent chromium complexes.

Complete or partial replacement of well-known five-membered chelating 2,2'-bipyridine (bipy) or 1,10-phenanthroline (phen) ligands with analogous didentate 2,2'-biimidazole (H2biim) provides novel perspectives for exploiting the latter pH-tuneable bridging unit for connecting inert trivalent chromium with cationic partners. The most simple homoleptic complex [Cr(H2biim)3]3+ and its stepwise deprotonated analogues are only poorly soluble in most solvents and their characterization is limited to some solid-state structures, in which the pseudo-octahedral [CrN6] units are found to be intermolecularly connected via peripheral N-H⋯X hydrogen bonds. Moreover, the associated high-energy stretching N-H vibrations drastically quench the targeted near infrared (NIR) CrIII-based phosphorescence, which makes these homoleptic building blocks incompatible with the design of molecular-based luminescent assemblies. Restricting the number of bound 2,2'-biimidazole ligands to a single unit in the challenging heteroleptic [Cr(phen)2(Hxbiim)](1+x)+ (x = 2-0) complexes overcomes the latter limitations and allows (i) the synthesis and characterization of these [CrN6] chromophores in the solid state and in solution, (ii) the stepwise and controlled deprotonation of the bound 2,2'-biimidazole ligand and (iii) the implementation of Cr-centered phosphorescence with energies, lifetimes and quantum yields adapted for using the latter chromophores as sensitizers in promising 'complex-as-ligand' strategies.

Sol-Gel Synthesis of TiO2 with Pectin and Their Efficiency in Solar Cells Sensitized by Quantum Dots.

In this study, titanium oxide TiO2 nanoparticles were produced using the sol-gel approach of green synthesis with pectin as the reducing agent. The synthetized TiO2 nanoparticles with pectin were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), visible light absorption (UV-Vis) and the BET method. The structure and morphology of the TiO2 powder were described with SEM, revealing uniform monodisperse grains with a distribution of 80% regarding sizes < 250 nm; the resulting crystal phase of synthetized TiO2 was identified as an anatase and rutile phase with a crystallinity size estimated between 27 and 40 nm. Also, the surface area was determined by nitrogen adsorption-desorption using the Brown-Emmet-Teller method, with a surface area calculated as 19.56 m2/g, typical of an IV type isotherm, indicating mesoporous NPs. UV-Vis spectra showed that sol-gel synthesis reduced the band gap from the 3.2 eV common value to 2.22 eV after estimating the optical band gap energy using the adsorption coefficient; this translates to a possible extended photo response to the visible region, improving photoactivity. In addition, the power conversion of the photoelectrode was compared based on similar assembly techniques of TiO2 electrode deposition. Quantum dot crystals were deposited ionically on the electrode surface, as two different paste formulations based on a pectin emulsifier were studied for layer deposition. The results confirm that the TiO2 paste with TiO2-synthesized powder maintained good connections between the nanocrystalline mesoporous grains and the deposited layers, with an efficiency of 1.23% with the transparent paste and 2.27% with the opaque paste. These results suggest that pectin could be used as a low-cost, functional sol-gel catalysis agent for the synthesis of controlled NPs of metal oxide. It demonstrates interesting optical properties, such as an increase in photo response, suggesting further applications to photocatalysts and biomedical features.

Spanish heart transplant registry. 35th official report of the Heart Failure Association of the Spanish Society of Cardiology.

INTRODUCTION AND OBJECTIVES: Our aim was to describe the characteristics and outcomes of heart transplants in Spain. METHODS: We analyzed trends in recipient and donor characteristics, recipient-donor interaction, surgical procedures, immunosuppression, and outcomes of patients included in the Spanish heart transplant registry from 2014 to 2023. Changes in survival were analyzed using the Kaplan-Meier method. RESULTS: In 2023, 325 cardiac transplants were performed (4.5% more than in the previous year), with a total of 2987 procedures from 2014 to 2023. There was a trend toward performing more transplants in women (29.2%), with etiologies other than cardiomyopathy (32.6%), and with better pretransplant status (less hepatic [12.5%], renal [glomerular filtration rate, 81.5mL/min/1.73 m2], and respiratory [8.7%] involvement). In 2023, the number of urgent transplants increased (44% of the total), especially those performed after circulatory support with extracorporeal membrane oxygenation (36% of total assistance), and transplants performed with donation after circulatory death (17.9%). Survival improved in the triennium from 2020 to 2022 compared with 2014 to 2016 (83.0% at 1 year from 2020-2022 vs 79.0% from 2014-2016). CONCLUSIONS: The number of transplants performed in Spain showed an upward trend, with recipients with better clinical status and an increasing use of donation after circulatory death. Survival improved in the last triennium.

Fever of unknown origin: A 12-year case series in Colombia.

BACKGROUND: Fever of unknown origin (FUO) is a diagnostic challenge with highly heterogeneous causes. Its etiology can change according to the studied regions, and the chance of reaching a diagnosis depends on available resources. The aim of this study is to describe the clinical characteristics, etiology and the usefulness of diagnostic aids in cases of FUO managed over 12 years in a Colombian reference center. METHODOLOGY: Single-institution retrospective case series. All cases of FUO between 2006 and 2017 were identified with the help of an electronic medical record search software. Cases of adults with fever for more than three weeks who remained undiagnosed after three days of hospitalization are described. RESULTS: Of 1,009 cases evaluated, 112 cases met the inclusion criteria (median age 43 years, 66% men). The etiologies identified were infectious (31.2%), inflammatory (20.5%), neoplastic (14.3%), and miscellaneous (2.7%) diseases. 31.2% remained without etiological diagnosis. The most frequent conditions were tuberculosis (17%), Hodgkin's lymphoma (7.1%), systemic lupus erythematosus (6.3%), disseminated histoplasmosis, and adult Still's disease. Contrast tomography and biopsies were the studies that most frequently supported or confirmed the final diagnosis. CONCLUSIONS: This series of contemporary Latin American cases suggests that the categories of FUO etiologies are similar to those reported in studies from developed countries, with tuberculosis being the most frequent cause in our setting. Our results highlight the importance of tomography-guided invasive studies in the diagnostic approach to FUO.

GLS and GLS2 Glutaminase Isoenzymes in the Antioxidant System of Cancer Cells.

A pathway frequently altered in cancer is glutaminolysis, whereby glutaminase (GA) catalyzes the main step as follows: the deamidation of glutamine to form glutamate and ammonium. There are two types of GA isozymes, named GLS and GLS2, which differ considerably in their expression patterns and can even perform opposing roles in cancer. GLS correlates with tumor growth and proliferation, while GLS2 can function as a context-dependent tumor suppressor. However, both isoenzymes have been described as essential molecules handling oxidant stress because of their involvement in glutathione production. We reviewed the literature to highlight the critical roles of GLS and GLS2 in restraining ROS and regulating both cellular signaling and metabolic stress due to their function as indirect antioxidant enzymes, as well as by modulating both reductive carboxylation and ferroptosis. Blocking GA activity appears to be a potential strategy in the dual activation of ferroptosis and inhibition of cancer cell growth in a ROS-mediated mechanism.

[Seronegative autoimmune hepatitis]. / Hepatitis autoinmune seronegativa.

Autoimmune hepatitis (AIH) is a rare, chronic, inflammatory, and necrotic liver disease characterized by the presence of autoantibodies. Its etiology is unknown. It affects 1 in 200 000 people annually in the US and occurs predominantly in women. Its presentation varies from asymptomatic forms to cirrhosis and acute liver failure and its diagnosis is based on the measurement of autoantibodies, such as antinuclear autoantibodies (ANA), anti-smooth muscle antibodies (ASMA) and anti-liver and kidney microsomal antibodies (anti-LKM). 1). 10% of HAIs do not present antibodies, being called seronegative HAI, requiring a liver biopsy for diagnosis. To date the evidence remains limited and different societies have issued suggestions and recommendations. For this reason, we believe it is relevant to carry out a bibliographic review on the subject, capturing in this document the important information for the understanding and management of this pathology.

La hepatitis autoinmune (HAI) es una enfermedad inflamatoria y necrótica del hígado, crónica e infrecuente caracterizada por la presencia de autoanticuerpos. Su etiología es desconocida. Afecta a 1 de cada 200 000 personas anualmente en los EE. UU. y se presenta predominantemente en mujeres. Su presentación varía desde formas asintomáticas hasta la cirrosis y falla hepática aguda y su diagnóstico se basa en la medición de autoanticuerpos, como los autoanticuerpos antinucleares (ANA), anticuerpos antimúsculo liso (ASMA) y anticuerpos antimicrosomales de hígado y riñón (anti-LKM-1). El 10% de las HAI no presentan anticuerpos, denominándose HAI seronegativa, necesitando biopsia hepática para el diagnóstico. Hasta la fecha la evidencia sigue siendo limitada y diferentes sociedades han emitido sugerencias y recomendaciones. Por tal motivo creemos relevante realizar una revisión bibliográfica sobre el tema plasmando en este documento la información importante para la compresión y el manejo de esta patología.

Molecular detection of Toxoplasma gondii in domestic and wild guinea pigs (Cavia spp.) from the Marangani district in Cuzco, Peru.

Toxoplasmosis is a foodborne disease caused by the protozoan Toxoplasma gondii, and transmitted to humans by eating raw or undercooked meat, mainly. Poultry, beef, and pork are the main meats consumed in Peru; despite this, guinea pig meat is also widely consumed. For this reason, the objective of this study was to molecularly detect T. gondii in domestic and wild guinea pigs from the Marangani district in Cuzco, Peru, and identify some risk factors associated with this pathogen. DNA was extracted from the brain tissue samples of guinea pigs (30 domestic and 30 wild), and PCR protocols were used to amplify the internal transcribed spacer (ITS-1) region and a 529 bp fragment from the T. gondii genome. T. gondii DNA was detected in 14 (23.3%) guinea pigs. T. gondii frequency was 33.3% in domestic guinea pigs and 13.3% in wild guinea pigs. Our results demonstrated that guinea pigs represent an important source for T. gondii infection in human populations in this locality.

Confronting the Unseen: A Journey Through Primary Intra-orbital Squamous Cell Carcinoma.

Cases of squamous cell carcinoma (SCC) that are primary in origin occur even more infrequently due to the lack of squamous epithelium that is typically present in the orbital region. When SCC occurs in the orbit, it is more commonly due to invasion or metastasis from a local site. We report an uncommon case of intra-orbital SCC in a 74-year-old male, which is likely of primary origin. Brain, face, orbital, and neck magnetic resonance imaging proceeded to gather more information on the extent of the patient's orbital malignancy, which showed significant orbital burden and intracranial extension. The biopsy was performed with final pathology results showing moderately differentiated SCC. The patient was discharged with a follow-up with oncology for chemotherapy and a follow-up with oculoplastics for surgical intervention in nine months, after completing a course of chemotherapy with irradiation. We provide this case to shed insight into the difficulties associated with the extremely uncommon occurrence of primary SCC of the orbit.

Discovery of GLPG3667, a Selective ATP Competitive Tyrosine Kinase 2 Inhibitor for the Treatment of Autoimmune Diseases.

Tyrosine kinase 2 (TYK2) mediates cytokine signaling through type 1 interferon, interleukin (IL)-12/IL-23, and the IL-10 family. There appears to be an association between TYK2 genetic variants and inflammatory conditions, and clinical evidence suggests that selective inhibition of TYK2 could produce a unique therapeutic profile. Here, we describe the discovery of compound 9 (GLPG3667), a reversible and selective TYK2 adenosine triphosphate competitive inhibitor in development for the treatment of inflammatory and autoimmune diseases. The preclinical pharmacokinetic profile was favorable, and TYK2 selectivity was confirmed in peripheral blood mononuclear cells and whole blood assays. Dermal ear inflammation was reduced in an IL-23-induced in vivo mouse model of psoriasis. GLPG3667 also completed a phase 1b study (NCT04594928) in patients with moderate-to-severe psoriasis where clinical effect was shown within the 4 weeks of treatment and it is now in phase 2 trials for the treatment of dermatomyositis (NCT05695950) and systemic lupus erythematosus (NCT05856448).

Association of Frailty with Postoperative Survival and Outcomes Following Hemodialysis Vascular Access Creation.

BACKGROUND: The literature suggests that for patients to experience the purported advantages of an arteriovenous fistula (AVF) over arteriovenous graft (AVG), a minimum survival of 18 months is required. With the vascular access guideline shift away from "Fistula First" toward shared decision making, patient survival after vascular access creation is a major factor to consider in optimal access selection. The objective of this study is to examine outcomes of vascular access in patients with short survival and factors associated with short survival, including frailty. METHODS: We performed a retrospective review of 200 access procedures performed between August 2018 and November 2020 at a single institution. Maturation was defined as the date when the surgeon deemed the access ready to be used for dialysis. A modified Risk Analysis Index (RAI) score was used to calculate frailty. RESULTS: Within 3 years after access creation, 55 (27.5%) patients were recorded as dead (mortality within 3 years of access creation [3YMORT]). In the 3YMORT group, 5 did not follow-up with the surgeon prior to death and 22/34 (65%) of AVF versus 15/16 (94%) of AVGs were deemed mature prior to death (P = 0.03). Of the accesses that matured, the median days to maturation for AVF was 69 (interquartile range [IQR] 53, 87) versus 28 (IQR 18, 32) for AVG (P < 0.001). Patients in the 3YMORT group were older (70.6 vs. 63.4, P = 0.004) and had a lower body mass index (24.8 vs. 27.4, P = 0.03). Patients in the 3YMORT group had higher prevalence of dysrhythmia (35% vs. 15%, P = 0.002), chronic obstructive pulmonary disorder (20% vs. 10%, P = 0.048) and dialysis dependence at the time of access creation (91% vs. 75%, P = 0.01). There was no significant difference in sex, white race, Hispanic ethnicity, coronary artery disease, congestive heart failure, previous coronary artery bypass graft or percutaneous coronary intervention, diabetes, hypertension, and peripheral arterial disease between the 2 groups. The 3YMORT group had a significantly higher prevalence of frailty (78% vs. 49%, P = 0.0002). Patients categorized as frail by the RAI had a significantly higher risk of 3YMORT (odds ratio [OR] 3.74, 95% confidence interval [CI] 1.82-7.66) compared to nonfrail patients. Patients categorized as very frail by the RAI had an even higher risk of 3YMORT (OR 4.20, 95% CI 1.95-9.05), compared to nonfrail patients. CONCLUSIONS: Patients with short life expectancy after vascular access creation may have high rates of AVF nonmaturation and longer time to maturation. Factors associated with high risk of mortality within 3 years of vascular access creation correlate well with factors included in the RAI frailty score. Patients who are frail or very frail may be appropriate candidates for AVG creation over AVF considering their high risk for short life expectancy.

Study of late toxicity biomarkers of locally advanced head and neck cancer patients treated with radiotherapy plus cisplatin or cetuximab points to the relevance of skin macrophages (TOX-TTCC-2015-01).

PURPOSE: Radiotherapy (RT) with concomitant cisplatin (CRT) or cetuximab (ERT) are accepted treatment options for locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). Long-term adverse events (AEs) have a vast impact on patients' quality of life. This study explored tissue biomarkers which could help predict late toxicity. METHODS/PATIENTS: Single-institution prospective study including patients aged ≥ 18 with histologically confirmed newly diagnosed LA-SCCHN treated with RT and either concomitant cisplatin q3w or weekly cetuximab, according to institutional protocols. All patients underwent pre- and post-treatment skin biopsies of neck regions included in the clinical target volume. Angiogenesis, macrophages, and extracellular matrix (ECM) markers were evaluated by immunohistochemistry (IHC). RESULTS: From April 15, 2016, to December 11, 2017; 31 patients were evaluated [CRT = 12 (38.7%) and ERT = 19 (61.3%)]. 27 patients (87%) had received induction chemotherapy. All patients finished RT as planned. IHC expression of vasculature (CD34) and collagen (Masson's Trichrome) did not differ significantly between and within CRT and ERT arms. Conversely, an increased CD68 and CD163 macrophage infiltration expression was observed after treatment, without significant impact of treatment modality. Patients with higher late toxicity showed lower expression of macrophage markers in pre-treatment samples compared with those with lower late toxicity, with statistically significant differences for CD68. CONCLUSIONS: Angiogenesis and ECM biomarkers did not differ significantly between CRT and ERT. Macrophage markers increased after both treatments and deserve further investigation as predictors of late toxicity in LA-SCCHN patients. [Protocol code: TOX-TTCC-2015-01/Spanish registry of clinical studies (REec): 2015-003012-21/Date of registration: 27/01/2016].

A Prospective Observational Study of Frailty in Geriatric Revitalization Aimed at Community-Dwelling Elderly.

(1) Background: The increasing life expectancy brings an increase in geriatric syndromes, specifically frailty. The literature shows that exercise is a key to preventing, or even reversing, frailty in community-dwelling populations. The main objective is to demonstrate how an intervention based on multicomponent exercise produces an improvement in frailty and pre-frailty in a community-dwelling population. (2) Methods: a prospective observational study of a multicomponent exercise program for geriatric revitalization with people aged over 65 holding Barthel Index scores equal to, or beyond, 90. The program was developed over 30 weeks, three times a week, in sessions lasting 45-50 min each. Frailty levels were registered by the Short Physical Performance Battery, FRAIL Questionnaire Screening Tool, and Timed "Up & Go" at the beginning of the program, 30 weeks later (at the end of the program), and following 13 weeks without training; (3) Results: 360 participants completed the program; a greater risk of frailty was found before the program started among older women living in urban areas, with a more elevated fat percentage, more baseline pathologies, and wider baseline medication use. Furthermore, heterogeneous results were observed both in training periods and in periods without physical activity. However, they are consistent over time and show improvement after training. They show a good correlation between TUG and SPPB; (4) Conclusions: A thirty-week multicomponent exercise program improves frailty and pre-frailty status in a community-dwelling population with no functional decline. Nevertheless, a lack of homogeneity is evident among the various tools used for measuring frailty over training periods and inactivity periods.