RESUMEN
BACKGROUND: Recently, we have identified a dysregulated protein signature in the esophageal epithelium of eosinophilic esophagitis (EoE) patients including proteins associated with inflammation and epithelial barrier function; however, the effect of proton pump inhibitor (PPI) treatment on this signature is unknown. Herein, we used a proteomic approach to investigate: (1) whether PPI treatment alters the esophageal epithelium protein profile observed in EoE patients and (2) whether the protein signature at baseline predicts PPI response. METHODS: We evaluated the protein signature of esophageal biopsies using a cohort of adult EoE (n = 25) patients and healthy controls (C) (n = 10). In EoE patients, esophageal biopsies were taken before (pre) and after (post) an 8-week PPI treatment, determining the histologic response. Eosinophil count PostPPI was used to classify the patients: ≥15 eosinophils/hpf as non-responders (non-responder) and < 15 eosinophils/hpf as responders (R). Protein signature was determined and differentially accumulated proteins were characterized to identify altered biological processes and signaling pathways. RESULTS: Comparative analysis of differentially accumulated proteins between groups revealed common signatures between three groups of patients with inflammation (responder-PrePPI, non-responder-PrePPI, and non-responder-PostPPI) and without inflammation (controls and responder-PostPPI). PPI therapy almost reversed the EoE specific esophageal protein signature, which is enriched in pathways associated with inflammation and epithelial barrier function, in responder-PostPPI. Furthermore, we identified a set of candidate proteins to differentiate responder-PrePPI and non-responder-PrePPI EoE patients before treatment. CONCLUSION: These findings provide evidence that PPI therapy reverses the alterations in esophageal inflammatory and epithelial proteins characterizing EoE, thereby providing new insights into the mechanism of PPI clinical response. Interestingly, our results also suggest that PPI response could be predicted at baseline in EoE.
RESUMEN
We report two novel prodrug Pt(IV) complexes with bis-organosilane ligands in axial positions: cis-dichloro(diamine)-trans-[3-(triethoxysilyl)propylcarbamate]platinum(IV) (Pt(IV)-biSi-1) and cis-dichloro(diisopropylamine)-trans-[3-(triethoxysilyl) propyl carbamate]platinum(IV) (Pt(IV)-biSi-2). Pt(IV)-biSi-2 demonstrated enhanced in vitro cytotoxicity against colon cancer cells (HCT 116 and HT-29) compared with cisplatin and Pt(IV)-biSi-1. Notably, Pt(IV)-biSi-2 exhibited higher cytotoxicity toward cancer cells and lower toxicity on nontumorigenic intestinal cells (HIEC6). In preclinical mouse models of colorectal cancer, Pt(IV)-biSi-2 outperformed cisplatin in reducing tumor growth at lower concentrations, with reduced side effects. Mechanistically, Pt(IV)-biSi-2 induced permanent DNA damage independent of p53 levels. DNA damage such as double-strand breaks marked by histone gH2Ax was permanent after treatment with Pt(IV)-biSi-2, in contrast to cisplatin's transient effects. Pt(IV)-biSi-2's faster reduction to Pt(II) species upon exposure to biological reductants supports its superior biological response. These findings unveil a novel strategy for designing Pt(IV) anticancer prodrugs with enhanced activity and specificity, offering therapeutic opportunities beyond conventional Pt drugs.
Asunto(s)
Antineoplásicos , Compuestos Organoplatinos , Profármacos , Profármacos/farmacología , Profármacos/química , Profármacos/síntesis química , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Animales , Compuestos Organoplatinos/farmacología , Compuestos Organoplatinos/química , Compuestos Organoplatinos/síntesis química , Ligandos , Ratones , Línea Celular Tumoral , Silanos/química , Silanos/farmacología , Relación Estructura-Actividad , Ensayos de Selección de Medicamentos Antitumorales , Células HT29RESUMEN
T cell-based immunotherapies for solid tumors have not achieved the clinical success observed in hematological malignancies, partially due to the immunosuppressive effect promoted by the tumor microenvironment, where PD-L1 and TGF-ß play a pivotal role. However, durable responses to immune checkpoint inhibitors remain limited to a minority of patients, while TGF-ß inhibitors have not reached the market yet. Here, we describe a bispecific antibody for dual blockade of PD-L1 and TFG-ß, termed AxF (scFv)2, under the premise that combination with T cell redirecting strategies would improve clinical benefit. The AxF (scFv)2 antibody was well expressed in mammalian and yeast cells, bound both targets and inhibited dose-dependently the corresponding signaling pathways in luminescence-based cellular reporter systems. Moreover, combined treatment with trispecific T-cell engagers (TriTE) or CAR-T cells significantly boosted T cell activation status and cytotoxic response in breast, lung and colorectal (CRC) cancer models. Importantly, the combination of an EpCAMxCD3×EGFR TriTE with the AxF (scFv)2 delayed CRC tumor growth in vivo and significantly enhanced survival compared to monotherapy with the trispecific antibody. In summary, we demonstrated the feasibility of concomitant blockade of PD-L1 and TGF-ß by a single molecule, as well as its therapeutic potential in combination with different T cell redirecting agents to overcome tumor microenvironment-mediated immunosuppression.
Asunto(s)
Anticuerpos Biespecíficos , Antineoplásicos , Neoplasias Colorrectales , Animales , Humanos , Anticuerpos Biespecíficos/farmacología , Anticuerpos Biespecíficos/uso terapéutico , Antineoplásicos/farmacología , Antígeno B7-H1 , Neoplasias Colorrectales/tratamiento farmacológico , Linfocitos T , Factor de Crecimiento Transformador beta , Microambiente TumoralRESUMEN
Global plastic production has increased exponentially in recent decades, and a significant part of it persists in the environment, where it degrades into microplastics and nanoplastics (MPs and NPs). These can enter in humans by ingestion, inhalation, and dermal routes, and there is scientific evidence that they are able to reach the systemic circulation and penetrate and accumulate in various tissues and organs. Neurodevelopmental toxicity of NPs is one of the most worrying effects, as they can cross the blood-brain barrier. In the following study, we analyzed, by transmission electron microscopy, the in vitro uptake of 30-nm polystyrene nanoplastics (PS-NPs) into human neural stem cells (NSCs), their accumulation and subcellular localization within the cell. Furthermore, we studied the effects of different concentrations of PS-NPs on cell death, proliferation, and cell differentiation using immunocytochemistry and quantitative real time PCR for specific markers. This study demonstrated that PS-NPs were able to enter the cell, probably by endocytosis, accumulate, and aggregated in human NSCs, without being detected in the nucleus, causing cell death by apoptosis and decreased cell proliferation. This study provides new insights into the interaction and effects of PS-NPs in human NSC and supports the scientific evidence for the involvement of nanoplastic in neurodevelopmental disorders.
Asunto(s)
Nanopartículas , Células-Madre Neurales , Contaminantes Químicos del Agua , Humanos , Microplásticos , Poliestirenos/toxicidad , Plásticos , ApoptosisRESUMEN
INTRODUCTION: All organs of any organism can be affected by helminths. They can be seen in a broad spectrum, from simple infestations to extensive, life-threatening involvement. Symptomatology is usually of chronic latent course. However, sometimes the presentation is acute and requires urgent surgical intervention. MATERIAL AND METHODS: We conducted a retrospective observational prospective recruitment study of patients undergoing emergency surgery for helminth infection from January 2000 to December 2019 at a university hospital. Sociodemographic and analytical variables, variables related to the clinical process, and the diagnostic test were analysed. Variables related to the surgical procedure and postoperative complications were also analysed. RESULTS: A total of 36 patients required emergency surgery for their helminth infection, which represented 0.26% of emergency abdominal surgeries. The mean age was 34.91 ± 21.5 years, with a predominance of men (69.4%). Most patients presented with pain in the right iliac fossa (69.4%), followed by symptoms compatible with intestinal obstruction (19.4%). The most frequent surgical interventions were appendectomy (38.9%) followed bowel resection (33.3%) and ileocecal resection (11.1%). Enterobious vermicularis and Anisakis simplex both together accounted for 75% of the sample. Statistically significant differences were identified in age (p < 0.001), diagnostic test performed (p = 0.032), intraoperative clinical diagnosis (p = 0.005) and surgical treatment received (p < 0.001). CONCLUSION: The frequency of emergency surgeries for intestinal helminth parasitism is decreasing. However, the majority of these are E. vermicularis and Anisakis simplex, which have distinctly different clinical presentations. Identification and recognition by physicians continue to be necessary for further postoperative management and possible complications.
Asunto(s)
Helmintiasis , Hospitales Universitarios , Parasitosis Intestinales , Humanos , Masculino , Femenino , Adulto , Estudios Retrospectivos , Helmintiasis/epidemiología , Helmintiasis/parasitología , Helmintiasis/cirugía , Persona de Mediana Edad , Parasitosis Intestinales/epidemiología , Parasitosis Intestinales/parasitología , Parasitosis Intestinales/cirugía , Adulto Joven , Adolescente , Anciano , Niño , Estudios ProspectivosRESUMEN
OBJECTIVE: To analyze the prognostic accuracy of the scores NEWS, qSOFA, GYM used in hospital emergency department (ED) in the assessment of elderly patients who consult for an infectious disease. METHODS: Data from the EDEN (Emergency Department and Elderly Need) cohort were used. This retrospective cohort included all patients aged ≥65 years seen in 52 Spanish EDs during two weeks (from 1-4-2019 to 7-4-2019 and 30/3/2020 to 5/4/2020) with an infectious disease diagnosis in the emergency department. Demographic variables, demographic variables, comorbidities, Charlson and Barthel index and needed scores parameters were recorded. The predictive capacity for 30-day mortality of each scale was estimated by calculating the area under the receiver operating characteristic (ROC) curve, and sensitivity and specificity were calculated for different cut-off points. The primary outcome variable was 30-day mortality. RESULTS: 6054 patients were analyzed. Median age was 80 years (IQR 73-87) and 45.3% women. 993 (16,4%) patients died. NEWS score had better AUC than qSOFA (0.765, 95CI: 0.725-0.806, versus 0.700, 95%CI: 0.653-0.746; Pâ¯<â¯.001) and GYM (0.716, 95%CI: 0.675-0.758; Pâ¯=â¯.024), and there was no difference between qSOFA and GYM (Pâ¯=â¯.345). The highest sensitivity scores for 30-day mortality were GYMâ¯≥â¯1 point (85.4%) while the qSOFA score ≥2 points showed high specificity. In the case of the NEWS scale, the cut-off point ≥4 showed high sensitivity, while the cut-off point NEWSâ¯≥â¯8 showed high specificity. CONCLUSION: NEWS score showed the highest predictive capacity for 30-day mortality. GYM score ≥1 showed a great sensitivity, while qSOFA ≥2 scores provide the highest specificity but lower sensitivity.
RESUMEN
Objetivos. Estudiar las variables de estado basal y de situación clínica a la llegada a urgencias relacionadas con la práctica de sondaje vesical (SV) en pacientes mayores, y si el SV está asociado a una evolución más compleja o grave. Método. Se incluyeron todos los pacientes de edad $ 65 años atendidos durante una semana en 52 servicios de urgencias (SU) españoles, que fueron clasificados en función de si se practicó o no SV en el SU. Se investigó la relación de SV con edad, sexo, 10 variables de comorbilidad, 7 de estado basal y 6 de situación clínica mediante un modelo de regresión logística multivariable. Se consideró la evolución como grave o compleja si existió necesidad de hospitalización, estancia prolongada, necesidad de residencia al alta o muerte. La relación entre edad y SV se exploró también mediante curvas spline cúbicas restringidas (SCR) ajustadas, tomando la edad de 65 años como referencia. (AU)
Objectives. The aims of this study in the Emergency Department and Elder Needs (EDEN) series were to explore associations between clinical variables on arrival at the ED (baseline) and the insertion of a bladder catheter, and the relation between catheterization and deterioration to a more complex or serious clinical state. Methods. Included were all patients aged 65 years or older attended during 1 week in 52 Spanish EDs. Patients were grouped according to whether a bladder catheter was or was not inserted in the ED. We used multivariable logistical regression to explore associations between catheterization and patient age, sex, 10 comorbidities, 7 baseline status variables, and 6 clinical variables. Progression was considered serious or complex if the patient died or required hospitalization, a prolonged hospital stay, or discharge to a care facility. We also explored the association between age and catheterization using adjusted restricted cubic spline (RCS) curves with a cutoff value of 65 years. (AU)
Asunto(s)
Humanos , Masculino , Femenino , Anciano , Anciano de 80 o más Años , Cateterismo Urinario/efectos adversos , Cateterismo Urinario/mortalidad , Geriatría , España , Servicio de Urgencia en Hospital , HospitalizaciónRESUMEN
OBJECTIVES: The aims of this study in the Emergency Department and Elder Needs (EDEN) series were to explore associations between clinical variables on arrival at the ED (baseline) and the insertion of a bladder catheter, and the relation between catheterization and deterioration to a more complex or serious clinical state. MATERIAL AND METHODS: Included were all patients aged 65 years or older attended during 1 week in 52 Spanish EDs. Patients were grouped according to whether a bladder catheter was or was not inserted in the ED. We used multivariable logistical regression to explore associations between catheterization and patient age, sex, 10 comorbidities, 7 baseline status variables, and 6 clinical variables. Progression was considered serious or complex if the patient died or required hospitalization, a prolonged hospital stay, or discharge to a care facility. We also explored the association between age and catheterization using adjusted restricted cubic spline (RCS) curves with a cutoff value of 65 years. RESULTS: Participating hospitals enrolled 24 573 patients; bladder catheters were inserted in 976 (4%). Of these, 44.3% were discharged from the ED. Fifteen of the 24 variables were independently associated with bladder catheterization. Factors with the strongest associations according to odds ratios (ORs) were impaired consciousness (OR, 2.50; 95% CI, 1.90-3.30), dehydration (OR, 2.24; 95% CI, 1.85-2.72), and male sex (OR, 2.12; 95% CI, 1.84- 2.44). Age 80 years or older was also associated with bladder catheterization (OR, 1.17; 95% CI, 1.01-1.358). The adjusted RCS curves showed a progressive linear increase in the probability of catheterization with age. The increase was constant in men and stabilized after the age of 85 years in women (P-interaction .001). Bladder catheterization was associated with hospitalization (OR, 2.31; 95% CI, 1.99-2.68), intensive care unit admission (OR, 4.64; 95% CI, 3.04-7.09), prolonged stay in the ED for discharged patients (OR, 2.28; 95% CI, 1.75-2.96), in-hospital death (OR, 1.99; 95% CI, 1.54-2.57), and 30-day death (OR, 1.66; 95% CI, 1.33-2.08). No associations were found between catheterization and prolonged hospital stay (OR, 1.11; 95% CI, 0.92-1.34) or need for a care facility on discharge (OR, 1.50; 95% CI, 0.98-2.29). CONCLUSION: Certain patient characteristics and baseline clinical conditions are associated with bladder catheterization in patients of advanced age. The main factors were decreased consciousness, dehydration, and male sex. Even after adjustment for related factors, catheterization is independently associated with progression to more complex or serious clinical states.
OBJETIVO: Estudiar las variables de estado basal y de situación clínica a la llegada a urgencias relacionadas con la práctica de sondaje vesical (SV) en pacientes mayores, y si el SV está asociado a una evolución más compleja o grave. METODO: Se incluyeron todos los pacientes de edad 65 años atendidos durante una semana en 52 servicios de urgencias (SU) españoles, que fueron clasificados en función de si se practicó o no SV en el SU. Se investigó la relación de SV con edad, sexo, 10 variables de comorbilidad, 7 de estado basal y 6 de situación clínica mediante un modelo de regresión logística multivariable. Se consideró la evolución como grave o compleja si existió necesidad de hospitalización, estancia prolongada, necesidad de residencia al alta o muerte. La relación entre edad y SV se exploró también mediante curvas spline cúbicas restringidas (SCR) ajustadas, tomando la edad de 65 años como referencia. RESULTADOS: Se incluyeron 24.573 pacientes, de los que 976 (4%) recibieron SV. De éstos, el 44,3% fueron dados de alta desde urgencias. De las 25 variables exploradas, 15 se relacionaron independientemente con el SV, y las más manifiestas fueron disminución de consciencia (OR = 2,50, IC 95% = 1,90-3,30), deshidratación (OR = 2,24, IC 95% = 1,85-2,72) y sexo masculino (OR = 2,12, IC 95% = 1,84-2,44). La edad 80 años también se asoció a SV (OR = 1,17, IC 95% = 1,01-1,358), y las curvas SCR ajustadas mostraron un incremento progresivo y lineal de la probabilidad de SV con la edad, constante en hombres y que se estabilizaba a partir de los 85 años en mujeres (p interacción 0,001). El SV se asoció a necesidad de hospitalización (OR = 2,31, IC 95% = 1,99-2,68), hospitalización en intensivos (OR = 4,64, IC 95% = 3,04-7,09), estancia prolongada en urgencias en los pacientes dados de alta (OR = 2,28, IC 95% = 1,75-2,96) y mortalidad intrahospitalaria (OR = 1,99, IC 95% = 1,54-2,57) y a 30 días (OR=1,66, IC 95% = 1,33-2,08), pero no con hospitalización prolongada (OR = 1,11, IC 95% = 0,92-1,34) ni con necesidad de residencia al alta (OR = 1,50, IC 95% = 0,98-2,29). CONCLUSIONES: Determinadas características del paciente mayor y de su estado clínico se asocian con realizar un SV en urgencias, entre las que destacan la disminución de consciencia, la deshidratación y el sexo masculino. Aun teniendo en cuenta los factores asociados a SV en urgencias, este procedimiento se asocia independientemente con evoluciones más complejas o graves.
Asunto(s)
Deshidratación , Vejiga Urinaria , Humanos , Masculino , Femenino , Anciano , Mortalidad Hospitalaria , Hospitalización , Cateterismo UrinarioRESUMEN
Orthodontics patients usual develop demineralization and present cavity caries lesions after six months. Minimally invasive procedures have been the goal in modern dental practice. The aim of this study was to evaluate the effect of ClinproTMXT Varnish, on the enamel surface roughness and severity of white spot lesions. Twenty premolars were submitted to bond brackets and experimental induction of demineralization and randomly divided into 2 groups: GI - fluoride varnish (Colgate Duraphat®); GII - Ionomeric Sealant (ClinproTMXT Varnish). The treatment was applied around the brackets. The surface roughness of specimens was analyzed, before treatment and 12 weeks after treatment by laser confocal microscopy, and the severity of the white spot lesion was by laser fluorescence device. The data were analyzed by non-parametric Wilcoxon and Mann-Whitney Test, at 5% significance, roughness percentage reduction was performed. The severity of demineralization decreased in both, GI (p = 0.005) and GII (p = 0.019). Enamel superficial roughness levels decreased in GI and GII. As well as the roughness percentage, being more expressive in the ClinproTMXT Varnish group (85,09%). Colgate Duraphat® or Clinpro™ XT Varnish reduced the severity of the demineralization and decreased the superficial roughness on the enamel. The Clinpro™ XT Varnish was superior to superficial roughness on enamel.
Asunto(s)
Caries Dental , Soportes Ortodóncicos , Desmineralización Dental , Humanos , Fluoruros Tópicos/farmacología , Esmalte Dental , Caries Dental/prevención & controlRESUMEN
Methotrexate is an essential drug in the treatment of childhood cancer that is not exempt from toxicities. Glucarpidase is a drug used to reduce the toxic concentration of plasma methotrexate in patients with delayed elimination or at risk of toxicity. We describe the characteristics of a cohort of pediatric patients that received glucarpidase and analyze its role in the treatment of toxicity induced by high doses of methotrexate (HDMTX). Retrospective observational study of all pediatric cancer patients who received glucarpidase between 2012 and 2022 at a single center. Fifteen patients were treated with a single dose of glucarpidase, eleven of them presented with acute lymphoblastic leukemia and received HDMTX at 5 g/m2 in 24-hour infusion. In eight patients, glucarpidase was administered during the first cycle of HDMTX. The indication in thirteen cases was acute renal failure with delayed elimination of plasma methotrexate. The median maximum creatinine was 1.22 mg/dl (0.68 2.01 mg/dl), with a median increase over its baseline level of 313%. All patients normalized renal function after glucarpidase administration, with a median methotrexate excretion time of 193 hours (42-312 hours). No grade ≥2 adverse events derived from carboxypeptidase administration. Eleven patients received new doses of HDMTX in subsequent cycles, without new episodes of serious toxicity. The use of glucarpidase is effective and safe in the treatment of acute renal failure and methotrexate elimination delay in pediatric cancer patients. Further HDMTX doses may be prescribed without additional toxicities.
RESUMEN
Congenital diaphragmatic hernia (CDH) is a relatively common and genetically heterogeneous structural birth defect associated with high mortality and morbidity. We describe eight unrelated families with an X-linked condition characterized by diaphragm defects, variable anterior body-wall anomalies, and/or facial dysmorphism. Using linkage analysis and exome or genome sequencing, we found that missense variants in plastin 3 (PLS3), a gene encoding an actin bundling protein, co-segregate with disease in all families. Loss-of-function variants in PLS3 have been previously associated with X-linked osteoporosis (MIM: 300910), so we used in silico protein modeling and a mouse model to address these seemingly disparate clinical phenotypes. The missense variants in individuals with CDH are located within the actin-binding domains of the protein but are not predicted to affect protein structure, whereas the variants in individuals with osteoporosis are predicted to result in loss of function. A mouse knockin model of a variant identified in one of the CDH-affected families, c.1497G>C (p.Trp499Cys), shows partial perinatal lethality and recapitulates the key findings of the human phenotype, including diaphragm and abdominal-wall defects. Both the mouse model and one adult human male with a CDH-associated PLS3 variant were observed to have increased rather than decreased bone mineral density. Together, these clinical and functional data in humans and mice reveal that specific missense variants affecting the actin-binding domains of PLS3 might have a gain-of-function effect and cause a Mendelian congenital disorder.
Asunto(s)
Hernias Diafragmáticas Congénitas , Osteoporosis , Adulto , Humanos , Masculino , Animales , Ratones , Hernias Diafragmáticas Congénitas/genética , Actinas/genética , Mutación Missense/genética , Osteoporosis/genéticaRESUMEN
This study upgrades the sustainability of environmental electrochemical technologies with a novel approach consisting of the in-situ cogeneration and use of two important oxidants, hydrogen peroxide (H2O2) and Caro's acid (H2SO5), manufactured with the same innovative cell. This reactor was equipped with a gas diffusion electrode (GDE) to generate cathodically H2O2, from oxygen reduction reaction, a boron doped diamond (BDD) electrode to obtain H2SO5, via anodic oxidation of dilute sulfuric acid, and a proton exchange membrane to separate the anodic and the cathodic compartment, preventing the scavenging effect of the interaction of oxidants. A special design of the inlet helps this cell to reach simultaneous efficiencies as high as 99% for H2O2 formation and 19.7% for Caro's acid formation, which means that the cogeneration reaches efficiencies over 100% in the uses of electric current to produce oxidants. The two oxidants' streams produced were used with different configurations for the degradation of three volatile organic compounds (benzene, toluene, and xylene) in a batch reactor equipped with a UVC-lamp. Among different alternatives studied, the combination H2SO5/H2O2 under UVC irradiation showed the best results in terms of degradation efficiency, demonstrating important synergisms as compared to the bare technologies.
Asunto(s)
Oxidantes , Contaminantes Químicos del Agua , Peróxido de Hidrógeno/química , Oxidación-Reducción , Electrodos , Boro/química , Diamante/química , Contaminantes Químicos del Agua/químicaRESUMEN
The United States Department of Agriculture (USDA) Division of Agricultural Select Agents and Toxins (DASAT) established a list of biological agents (Select Agents List) that threaten crops of economic importance to the United States and regulates the procedures governing containment, incident response, and the security of entities working with them. Every 2 years the USDA DASAT reviews their select agent list, utilizing assessments by subject matter experts (SMEs) to rank the agents. We explored the applicability of multi-criteria decision analysis (MCDA) techniques and a decision support framework (DSF) to support the USDA DASAT biennial review process. The evaluation includes both current and non-select agents to provide a robust assessment. We initially conducted a literature review of 16 pathogens against 9 criteria for assessing plant health and bioterrorism risk and documented the findings to support this analysis. Technical review of published data and associated scoring recommendations by pathogen-specific SMEs was found to be critical for ensuring accuracy. Scoring criteria were adopted to ensure consistency. The MCDA supported the expectation that select agents would rank high on the relative risk scale when considering the agricultural consequences of a bioterrorism attack; however, application of analytical thresholds as a basis for designating select agents led to some exceptions to current designations. A second analytical approach used agent-specific data to designate key criteria in a DSF logic tree format to identify pathogens of low concern that can be ruled out for further consideration as select agents. Both the MCDA and DSF approaches arrived at similar conclusions, suggesting the value of employing the two analytical approaches to add robustness for decision making.
RESUMEN
Giant cell arteritis (GCA), known as temporal arteritis, is a serious condition requiring immediate treatment to prevent complications. GCA can be difficult to diagnose, especially in emergency department (ED) settings where ophthalmology and rheumatology services may be unavailable. Temporal artery ultrasound (TAUS) is a valuable tool for diagnosing GCA. In the ED, TAUS can be used to quickly rule out GCA and avoid unindicated steroid treatment, which can cause serious morbidity in elderly patients. This article discusses the use of TAUS for evaluating patients with suspected GCA in the ED and its potential to expedite treatment and ensure appropriate, timely follow-up for patients with this potential vision and life-threatening condition.
RESUMEN
Abstract Orthodontics patients usual develop demineralization and present cavity caries lesions after six months. Minimally invasive procedures have been the goal in modern dental practice. The aim of this study was to evaluate the effect of ClinproTMXT Varnish, on the enamel surface roughness and severity of white spot lesions. Twenty premolars were submitted to bond brackets and experimental induction of demineralization and randomly divided into 2 groups: GI - fluoride varnish (Colgate Duraphat®); GII - Ionomeric Sealant (ClinproTMXT Varnish). The treatment was applied around the brackets. The surface roughness of specimens was analyzed, before treatment and 12 weeks after treatment by laser confocal microscopy, and the severity of the white spot lesion was by laser fluorescence device. The data were analyzed by non-parametric Wilcoxon and Mann-Whitney Test, at 5% significance, roughness percentage reduction was performed. The severity of demineralization decreased in both, GI (p = 0.005) and GII (p = 0.019). Enamel superficial roughness levels decreased in GI and GII. As well as the roughness percentage, being more expressive in the ClinproTMXT Varnish group (85,09%). Colgate Duraphat® or Clinpro™ XT Varnish reduced the severity of the demineralization and decreased the superficial roughness on the enamel. The Clinpro™ XT Varnish was superior to superficial roughness on enamel.
Resumo Pacientes ortodônticos geralmente desenvolvem desmineralização e apresentam lesões de cárie após seis meses de tratamento. Procedimentos minimamente invasivos têm sido o objetivo na prática odontológica moderna. O objetivo deste estudo foi avaliar o efeito do ClinproTM XT selante ionomérico, ao redor do bráquete, com relação a rugosidade superficial do esmalte e a severidade da lesão induzida. Vinte pré-molares foram submetidos a colagem de bráquetes e indução experimental de desmineralização e divididos aleatoriamente em 2 grupos: GI - verniz fluoretado (Colgate Duraphat®); GII - Selante Ionomérico (ClinproTM XT). O tratamento foi aplicado ao redor dos bráquetes. A rugosidade da superfície dos espécimes foi analisada, antes do tratamento e 12 semanas após o tratamento por microscopia confocal a laser e severidade da lesão de mancha branca por dispositivo de fluorescência a laser. Os dados foram analisados pelo teste não paramétrico de Wilcoxon e Mann-Whitney, a 5% de significância. A taxa de redução da lesão foi calculada. A severidade da desmineralização diminuiu tanto no GI (p = 0,005) quanto no GII (p = 0,019). Os níveis de rugosidade superficial do esmalte diminuíram no GI e GII, assim como o percentual de rugosidade, sendo mais expressivo no grupo ClinproTMXT (85,09%). Colgate Duraphat® e Clinpro™ XT reduziram a severidade da desmineralização e diminuíram a rugosidade superficial do esmalte. O selante ionomérico Clinpro™ XT foi superior na redução percentual de rugosidade.
RESUMEN
OBJECTIVES: To analyze the impact of the COVID-19 pandemic on Spanish emergency department (ED) care for patients aged 65 years or older during the first wave vs. a pre-pandemic period. MATERIAL AND METHODS: Retrospective cross-sectional study of a COVID-19 portion of the EDEN project (Emergency Department and Elder Needs). The EDEN-COVID cohort included all patients aged 65 years or more who were treated in 52 EDs on 7 consecutive days early in the pandemic. We analyzed care variables, discharge diagnoses, use of diagnostic and therapeutic resources, use of observation units, need for hospitalization, rehospitalization, and mortality. These data were compared with data for an EDEN cohort in the same age group recruited during a similar period the year before the pandemic. RESULTS: The 52 participating hospital EDs attended 33 711 emergencies during the pandemic vs. 96 173 emergencies in the pre-COVID period, representing a 61.7% reduction during the pandemic. Patients aged 65 years or older accounted for 28.8% of the caseload during the COVID-19 period and 26.4% of the earlier cohort (P .001). The COVID-19 caseload included more men (51.0%). Comorbidity and polypharmacy were more prevalent in the pandemic cohort than in the earlier one (comorbidity, 92.6% vs. 91.6%; polypharmacy, 65.2% vs. 63.6%). More esturesources (analgesics, antibiotics, heparins, bronchodilators, and corticosteroids) were applied in the pandemic period, and common diagnoses were made less often. Observation wards were used more often (for 37.8% vs. 26.2% in the earlier period), and hospital admissions were more frequent (in 56.0% vs. 25.3% before the pandemic). Mortality was higher during the pandemic than in the earlier cohort either in ED (1.8% vs 0.5%) and during hospitalization (11.5 vs 2.9%). CONCLUSION: The proportion of patients aged 65 years or older decreased in the participating Spanish EDs. However, more resources were required and the pattern of diagnoses changed. Observation ward stays were longer, and admissions and mortality increased over the numbers seen in the reference period.
OBJETIVO: Analizar el impacto de la pandemia COVID-19 sobre la asistencia a las personas mayores ($ 65 años) en los servicios de urgencias hospitalarios (SUH) españoles durante la primera oleada pandémica, comparándola con un periodo previo. METODO: Estudio transversal retrospectivo de la cohorte EDEN-COVID (Emergency Department and Elder Needs during COVID), que incluyó a todos los pacientes $ 65 años atendidos en 52 SUH españoles durante 7 días consecutivos de un periodo pandémico. Se analizaron variables asistenciales, diagnósticos de alta, consumo de recursos diagnósticos y terapéuticos, utilización de las unidades de observación, necesidad de ingreso, rehospitalización y mortalidad. Estos datos se compararon con la cohorte EDEN (Emergency Department and Elder Needs), que reclutó a pacientes del mismogrupo de edad durante un periodo similar del año anterior. RESULTADOS: Durante el periodo COVID-19 se atendieron 33.711 episodios en los 52 SUH participantes, frente a 96.173 del periodo pre-COVID, lo que supone una disminución de la demanda de 61,7%. La proporción de asistencias a pacientes de 65 o más años fue de 28,8% en el periodo COVID-19 y 26,4% en el periodo previo (p 0,001). Durante el periodo COVID hubo mayor proporción de hombres (51,0% vs 44,9%), mayor comorbilidad (92,6% vs 91,6%) y polifarmacia (65,2% vs 63,6%), mayor uso de recursos, de analgésicos, antibióticos, heparinas, broncodilatadores y corticoides, menor proporción de los diagnósticos más habituales, mayor utilización de las unidades de observación (37,8% vs 26,2%) y un incremento de la proporción de ingresos (56,0% vs 25,3%), y de mortalidad en urgencias (1,8% vs 0,5%) y durante la hospitalización (11,5% vs 2,9%). CONCLUSIONES: La primera ola de la pandemia COVID-19 ha provocado una disminución global de las asistencias a personas mayores ($ 65 años) en los SUH españoles analizados, mayor consumo de recursos, un mapa diferente de procesos diagnósticos asistidos y un aumento proporcional de estancias en observación, de ingresos y de mortalidad, respecto al periodo de referencia.
Asunto(s)
COVID-19 , Pandemias , Masculino , Humanos , Anciano , Estudios de Cohortes , Estudios Retrospectivos , Estudios Transversales , Urgencias Médicas , COVID-19/epidemiología , COVID-19/terapia , Servicio de Urgencia en HospitalRESUMEN
BACKGROUND: Despite the recognized impact of diet on non-communicable diseases, the association between the Mediterranean diet and periodontal diseases is still uncertain. This study aimed to determine the association between adherence to the Mediterranean Diet Index (MDI) and self-reported gingival health status in Chilean adults, exploring the feasibility of using validated web-based survey questionnaires. METHODOLOGY: Cross-sectional data were collected from a representative sample of a population of Chilean adults (18-60 years old) using a low-cost and time-saving methodology. By the PsyToolkit platform, anonymous survey data were downloaded and analyzed in bivariate (crude) and backward stepwise selection multivariate logistic regression models adjusted for sociodemographic determinants, smoking, and dental attendance using STATA 17. Odds ratios (OR) [95% confidence intervals] were estimated. RESULTS: In total, 351 complete statistical data were mostly obtained from female university students who had never smoked and reported having visited a dentist in the previous year. Multivariate regression models showed an association between MDI and very good/good gingival health status (OR 1.18 [95% CI 1.04-1.34], p=0.013), absence of bleeding on toothbrushing (OR 1.12 [95% CI 1.01-1.25], p=0.035), and absence of clinical signs of gingival inflammation (OR 1.24 [95% CI 1.10-1.40], p<0.001), after controlling for age, sex, educational level, smoking, and dental attendance. CONCLUSIONS: We associated adherence to the Mediterranean diet with better self-reported gingival health status in a population of Chilean adults in an entirely web-based research environment. Longitudinal studies with random sampling are required to establish the effect of diet on gingival and periodontal health. Nevertheless, this evidence could contribute to the design of low-cost surveillance programs to reduce the burden of periodontal disease and related "common risk factors".
Asunto(s)
Dieta Mediterránea , Gingivitis , Enfermedades Periodontales , Humanos , Adulto , Femenino , Adolescente , Adulto Joven , Persona de Mediana Edad , Estudios Transversales , Autoinforme , Chile/epidemiología , Enfermedades Periodontales/epidemiologíaRESUMEN
BACKGROUND: Permanent supportive housing (PSH)-subsidized housing paired with support services such as case management-is a key part of national strategic plans to end homelessness. PSH tenants face high overdose risk due to a confluence of individual and environmental risk factors, yet little research has examined overdose prevention in PSH. METHODS: We describe the protocol for a hybrid type 3 stepped-wedge cluster randomized controlled trial (RCT) of overdose prevention practice implementation in PSH. We adapted evidence-based overdose prevention practices and implementation strategies for PSH using input from stakeholder focus groups. The trial will include 20 PSH buildings (with building size ranging from 20 to over 150 tenants) across New York City and New York's Capital Region. Buildings will be randomized to one of four 6-month intervention waves during which they will receive a package of implementation support including training in using a PSH Overdose Prevention (POP) Toolkit, time-limited practice facilitation, and learning collaboratives delivered to staff and tenant implementation champions appointed by each building. The primary outcome is building-level fidelity to a defined list of overdose prevention practices. Secondary and exploratory implementation and effectiveness outcomes will be examined using PSH staff and tenant survey questionnaires, and analysis of tenant Medicaid data. We will explore factors related to implementation success, including barriers and facilitators, using qualitative interviews with key stakeholders. The project is being conducted through an academic-community partnership, and an Advisory Board including PSH tenants and other key stakeholders will be engaged in all stages of the project. DISCUSSION: We describe the protocol for a hybrid type 3 stepped-wedge cluster RCT of overdose prevention practice implementation in PSH. This study will be the first controlled trial of overdose prevention implementation in PSH settings. The research will make a significant impact by testing and informing future implementation strategies to prevent overdose for a population at particularly high risk for overdose mortality. Findings from this PSH-focused research are expected to be broadly applicable to other housing settings and settings serving people experiencing homelessness. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05786222 , registered 27 March 2023.
Asunto(s)
Sobredosis de Droga , Personas con Mala Vivienda , Estados Unidos , Humanos , Sobredosis de Droga/prevención & control , Manejo de Caso , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Undifferentiated anaplastic thyroid tumours are uncommon and constitute a diagnostic challenge on fine needle aspiration. A case showing large, single neoplastic cells in a background of Hashimoto's disease is presented.
Asunto(s)
Enfermedad de Hashimoto , Neoplasias de la Tiroides , Humanos , Enfermedad de Hashimoto/complicaciones , Enfermedad de Hashimoto/diagnóstico , Enfermedad de Hashimoto/patología , Neoplasias de la Tiroides/complicaciones , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/patología , Biopsia con Aguja FinaRESUMEN
SANT (sclerosing angiomatoid nodular transformation) tumor is a rare splenic tumor of unknown etiology and vascular lineage, first described in 2004. Most cases are asymptomatic, although cases of anemia or abdominal pain in association with growth have been described. Spontaneous ruptures have not been described. Radiologically it presents a radial pattern with centripetal filling in dynamic MRI, being a characteristic feature, but not pathognomonic. It may present hypermetabolism in PET-CT. Its incidence is increasing since its description as an independent clinical and histopathological entity, especially in the oncological patients follow-up. Due to its radiological resemblance to metastatic lesions and its growth despite being a vascular lesion, splenectomy is indicated following the principles of oncologic surgery until a definitive diagnosis is made. It presents a benign behavior, requiring neither treatment nor specific subsequent surveillance. Two diagnosed cases of SANT are presented, as well as a review of the clinical, radiological and histopathological characteristics of this little-known splenic lesion.