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The successful translation of therapeutic nucleic acids (NAs) for the treatment of neurological disorders depends on their safe and efficient delivery to neural cells, in particular neurons. DNA nanostructures can be a promising NAs delivery vehicle. Nonetheless, the potential of DNA nanostructures for neuronal cell delivery of therapeutic NAs is unexplored. Here, tetrahedral DNA nanostructures (TDN) as siRNA delivery scaffolds to neuronal cells, exploring the influence of functionalization with two different reported neuronal targeting ligands: C4-3 RNA aptamer and Tet1 peptide are investigated. Nanostructures are characterized in vitro, as well as in silico using molecular dynamic simulations to better understand the overall TDN structural stability. Enhancement of neuronal cell uptake of TDN functionalized with the C4-3 Aptamer (TDN-Apt), not only in neuronal cell lines but also in primary neuronal cell cultures is demonstrated. Additionally, TDN and TDN-Apt nanostructures carrying siRNA are shown to promote silencing in a process aided by chloroquine-induced endosomal disruption. This work presents a thorough workflow for the structural and functional characterization of the proposed TDN as a nano-scaffold for neuronal delivery of therapeutic NAs and for targeting ligands evaluation, contributing to the future development of new neuronal drug delivery systems based on DNA nanostructures.
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ADN , Nanoestructuras , Neuronas , ARN Interferente Pequeño , Nanoestructuras/química , Neuronas/metabolismo , ADN/química , ADN/metabolismo , Animales , Humanos , Aptámeros de Nucleótidos/química , Ácidos Nucleicos/química , Simulación de Dinámica MolecularRESUMEN
New pyridine-based chalcones 4a-h and pyrazolines 5a-h (N-acetyl), 6a-h (N-phenyl), and 7a-h (N-4-chlorophenyl) were synthesized and evaluated by the National Cancer Institute (NCI) against 60 different human cancer cell lines. Pyrazolines 6a, 6c-h, and 7a-h satisfied the pre-determined threshold inhibition criteria, obtaining that compounds 6c and 6f exhibited high antiproliferative activity, reaching submicromolar GI50 values from 0.38 to 0.45 µM, respectively. Moreover, compound 7g (4-CH3) exhibited the highest cytostatic activity of these series against different cancer cell lines from leukemia, nonsmall cell lung, colon, ovarian, renal, and prostate cancer, with LC50 values ranging from 5.41 to 8.35 µM, showing better cytotoxic activity than doxorubicin. Furthermore, the compounds were tested for antibacterial and antiplasmodial activities. Chalcone 4c was the most active with minimal inhibitory concentration (MIC) = 2 µg/mL against methicillin-resistant Staphylococcus aureus (MRSA), while the pyrazoline 6h showed a MIC = 8 µg/mL against Neisseria gonorrhoeae. For anti-Plasmodium falciparum activity, the chalcones display higher activity with EC50 values ranging from 10.26 to 10.94 µg/mL. Docking studies were conducted against relevant proteins from P. falciparum, exhibiting the minimum binding energy with plasmepsin II. In vivo toxicity assay in Galleria mellonella suggests that most compounds are low or nontoxic.
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Antibacterianos , Antimaláricos , Antineoplásicos , Chalconas , Pruebas de Sensibilidad Microbiana , Plasmodium falciparum , Pirazoles , Piridinas , Humanos , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Chalconas/farmacología , Chalconas/síntesis química , Chalconas/química , Antibacterianos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Línea Celular Tumoral , Relación Estructura-Actividad , Plasmodium falciparum/efectos de los fármacos , Pirazoles/farmacología , Pirazoles/química , Pirazoles/síntesis química , Piridinas/farmacología , Piridinas/química , Piridinas/síntesis química , Antimaláricos/farmacología , Antimaláricos/síntesis química , Antimaláricos/química , Simulación del Acoplamiento Molecular , Ensayos de Selección de Medicamentos Antitumorales , Proliferación Celular/efectos de los fármacos , Estructura Molecular , Animales , Relación Dosis-Respuesta a Droga , Neisseria gonorrhoeae/efectos de los fármacosRESUMEN
BACKGROUND: Olive and sunflower seeds are by-products generated in large amounts by the plant oil industry. The technological and biological properties of plant-based substrates, especially protein hydrolysates, have increased their use as functional ingredients for food matrices. The present study evaluates the physical and oxidative stabilities of 50 g kg-1 fish oil-in-water emulsions where protein hydrolysates from olive and sunflower seeds were incorporated at 20 g kg-1 protein as natural emulsifiers. The goal was to investigate the effect of protein source (i.e. olive and sunflower seeds), enzyme (i.e. subtilisin and trypsin) and degree of hydrolysis (5%, 8% and 11%) on the ability of the hydrolysate to stabilize the emulsion and retard lipid oxidation over a 7-day storage period. RESULTS: The plant protein hydrolysates displayed different emulsifying and antioxidant capacities when incorporated into the fish oil-in-water emulsions. The hydrolysates with degrees of hydrolysis (DH) of 5%, especially those from sunflower seed meal, provided higher physical stability, regardless of the enzymatic treatment. For example, the average D [2, 3] values for the emulsions containing sunflower subtilisin hydrolysates at DH 5% only slightly increased from 1.21 ± 0.02 µm (day 0) to 2.01 ± 0.04 µm (day 7). Moreover, the emulsions stabilized with sunflower or olive seed hydrolysates at DH 5% were stable against lipid oxidation throughout the storage experiment, with no significant variation in the oxidation indices between days 0 and 4. CONCLUSION: The results of the present study support the use of sunflower seed hydrolysates at DH 5% as natural emulsifiers for fish oil-in-water emulsions, providing both physical and chemical stability against lipid oxidation. © 2024 Society of Chemical Industry.
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Emulsiones , Aceites de Pescado , Helianthus , Olea , Oxidación-Reducción , Proteínas de Plantas , Hidrolisados de Proteína , Semillas , Emulsiones/química , Helianthus/química , Olea/química , Hidrolisados de Proteína/química , Aceites de Pescado/química , Semillas/química , Proteínas de Plantas/química , Agua/química , Antioxidantes/química , Hidrólisis , Emulsionantes/químicaRESUMEN
BACKGROUND: Rheumatoid arthritis (RA) is a chronic disease that affects different areas of the patient's body. Patient education and health literacy is essential for them to participate actively in follow-up. OBJECTIVES: The aim of this study was to assess differences between clinimetric measurements done by a medical team and patient-reported outcome measures (PROMs) in RA and understand the impact of patient education strategies in order to identify differences between RA assessment methods. METHODS: This is a longitudinal cohort study. It included adult patients with RA and access to digital tools. These were divided into 3 groups by type of education. Group 1 included patients who participated in a multicomponent RA educational program. Group 2 did not have this multicomponent RA education. Group 3 did not receive any education. The 3 groups performed PROMs. Disease activity scales, functional class, and quality of life were measured. Univariate and bivariate analysis (χ 2 and Wilcoxon for paired data) were done. RESULTS: Twenty-eight patients were included in group 1, 26 in group 2, and 37 in group 3. All were women. In group 1, there were no significant differences in clinimetrics between the medical team and patient's PROMs except for fatigue. In group 2 and group 3, significant differences were found. The RAPID3 and PAS variables did not show significant differences when analyzed by intervention subgroups. CONCLUSIONS: This study shows no differences between clinimetrics/PROMs for patients with a high-level education on RA and physicians. On the other hand, when patient did not have any RA education, the clinimetric results differed from physician measurement.
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Artritis Reumatoide , Educación del Paciente como Asunto , Medición de Resultados Informados por el Paciente , Calidad de Vida , Humanos , Artritis Reumatoide/terapia , Artritis Reumatoide/diagnóstico , Femenino , Persona de Mediana Edad , Educación del Paciente como Asunto/métodos , Estudios Longitudinales , Masculino , Adulto , Alfabetización en Salud/métodos , Alfabetización en Salud/estadística & datos numéricos , Anciano , Índice de Severidad de la EnfermedadRESUMEN
Despite extensive research on cancer care during the COVID-19 pandemic, evidence on the impact on prediagnostic time intervals is lacking. To better understand how COVID-19 changed the pathway to diagnosis of cancer, we examined the length of intervals from symptom onset to diagnosis for 13 common cancer types with known clinical stage over 1-year nonpandemic period (March 2019 to March 2020; N = 844) and three biannual COVID periods (March 2020 to September 2021; N = 1172). We analyzed the patient interval (from first symptoms to presentation to a physician), the primary care/emergency department interval (from presentation with relevant symptoms to a primary care or emergency department physician to referral to a hospital-based diagnosis center) and the hospital interval (from referral to diagnosis). Compared to nonpandemic data, there were significant changes across COVID periods. The pandemic mostly impacted patient intervals for cancers diagnosed over the first 6 months after onset in March 2020. Overall median patient intervals were longest in the early COVID period (39 [IQR 22-64] days) and shortest in the nonpandemic period (20 [IQR 13-30] days; Kruskal-Wallis test [χ2 ], P < .0001). Differences in clinical stage between periods were relevant, with cancers from the mid-period (September 2020 to March 2021) showing the most advanced stage. A shift to later stage was plausibly a result of delayed intervals in the early COVID period. Since intervals are eventually relevant to prognosis, our results provide a baseline against which the impact of improvement strategies to minimize the negative outcomes of COVID-19-associated cancer delays can be assessed and implemented.
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COVID-19 , Neoplasias , Humanos , Pandemias , COVID-19/epidemiología , Estudios Retrospectivos , Vías Clínicas , Derivación y Consulta , Neoplasias/diagnóstico , Neoplasias/epidemiologíaRESUMEN
This study compares noise and signal-to-noise ratio (SNR) in direct detection and coherent detection fiber-based distributed acoustic sensing (DAS) systems. Both detection schemes employ the dynamic analysis of Rayleigh-backscattered light in phase-sensitive optical time-domain reflectometry (ΦOTDR) systems. Through theoretical and experimental analysis, it is determined that for photodetection filters with a sufficiently narrow bandwidth, the SNR performance of both detection schemes is comparable. However, for filters with poor selectivity, coherent detection was found to exhibit superior performance. These findings provide crucial guidelines for the design of high-performance time-domain DAS systems.
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Heart failure with preserved ejection fraction (HFpEF) is now the most common form of heart failure (HF). This syndrome is associated with an elevated morbi-mortality, and effective therapies are urgently needed. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are the first pharmacological class that has demonstrated to reduce hospitalization and cardiovascular mortality in large clinical trials in HFpEF. Furthermore, the dual SGLT 1/2 inhibitor sotagliflozin has shown a reduction in cardiovascular outcomes in diabetic HF patients, regardless of ejection fraction Sotagliflozin on Cardiovascular Events in Patients with Type 2 Diabetes Post Worsening Heart Failure (SOLOIST-WHF) Trial, and prevents the development of HF in patients with diabetes and chronic kidney disease Sotagliflozin on Cardiovascular and Renal Events in Patients with Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk (SCORED) trial. The major objective of the Sotagliflozin in Heart Failure With Preserved Ejection Fraction Patients (SOTA-P-CARDIA) trial (NCT05562063) is to investigate whether the observed cardiorenal benefits of sotagliflozin in HF patients with diabetes can be extended to a non-diabetic population. The SOTA-P-CARDIA is a prospective, randomized, double-blinded, placebo-controlled study that will randomize non-diabetic patients with the universal definition of HFpEF (ejection fraction > 50% assessed the day of randomization). Qualifying patients will be randomized, in blocks of 4, to receive either sotagliflozin or placebo for a period of 6 months. The primary outcome is changes in left ventricular mass by cardiac magnetic resonance from randomization to end of the study between the groups. Secondary end points include changes in peak VO2; myocardial mechanics, interstitial myocardial fibrosis, and volume of epicardial adipose tissue; distance in the 6-min walk test; and quality of life. Finally, the authors expect that this trial will help to clarify the potential benefits of the use of sotagliflozin in non-diabetic HFpEF patients.
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Aim: Evidence on time-based metrics for cancers diagnosed through emergency presentation is lacking. We examined the duration of intervals from first symptoms to cancer diagnosis in the emergency versus primary care (PC) presentation route. Methods: Retrospective study of outpatients diagnosed with 15 solid cancers over 5 years. The outcome was the length of prediagnostic intervals by diagnostic route. Results: Median intervals in emergency presenters (n = 3167) were shorter than in PC presenters (n = 2215). However, intervals in emergency presenters with three or more prior PC consultations were similar to PC but remarkably longer than in those with one or two and no consultations. Conclusion: As we provide new interval measures for the emergency diagnostic pathway, results highlight the contribution of prior consultations to interval lengths.
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Diagnóstico Tardío , Neoplasias , Humanos , Estudios Retrospectivos , Neoplasias/diagnóstico , Neoplasias/terapia , Derivación y Consulta , Factores de TiempoRESUMEN
The development of new antimalarials is paramount to keep the goals on reduction of malaria cases in endemic regions. The search for quality hits has been challenging as many inhibitory molecules may not progress to the next development stage. The aim of this work was to screen an in-house library of heterocyclic compounds (HCUV) for antimalarial activity combining computational predictions and phenotypic techniques to find quality hits. The physicochemical determinants, pharmacokinetic properties (ADME), and drug-likeness of HCUV were evaluated in silico, and compounds were selected for structure-based virtual screening and in vitro analysis. Seven Plasmodium target proteins were selected from the DrugBank Database, and ligands and receptors were processed using UCSF Chimera and Open Babel before being subjected to docking using Autodock Vina and Autodock 4. Growth inhibition of P. falciparum (3D7) cultures was tested by SYBR Green assays, and toxicity was assessed using hemolytic activity tests and the Galleria mellonella in vivo model. From a total of 792 compounds, 341 with good ADME properties, drug-likeness, and no interference structures were subjected to in vitro analysis. Eight compounds showed IC50 ranging from 0.175 to 0.990 µM, and active compounds included pyridyl-diaminopyrimido-diazepines, pyridyl-N-acetyl- and pyridyl-N-phenyl-pyrazoline derivatives. The most potent compound (UV802, IC50 0.178 µM) showed no toxicophoric and was predicted to interact with P. falciparum 1-cysperoxidredoxin (PfPrx1). For the remaining 7 hits (IC50 < 1 µM), 3 showed in silico binding to PfPrx1, one was predicted to bind the haloacid dehalogenase-like hydrolase and plasmepsin II, and one interacted with the plasmodial heat shock protein 90.
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Antimaláricos , Malaria Falciparum , Malaria , Humanos , Antimaláricos/uso terapéutico , Plasmodium falciparum , Malaria/tratamiento farmacológico , Malaria Falciparum/tratamiento farmacológico , Simulación del Acoplamiento MolecularRESUMEN
Emulsions are implemented in the fabrication of a wide array of foods and therefore are of great importance in food science. However, the application of emulsions in food production is restricted by two main obstacles, that is, physical and oxidative stability. The former has been comprehensively reviewed somewhere else, but our literature review indicated that there is a prominent ground for reviewing the latter across all kinds of emulsions. Therefore, the present study was formulated in order to review oxidation and oxidative stability in emulsions. In doing so, different measures to render oxidative stability to emulsions are reviewed after introducing lipid oxidation reactions and methods to measure lipid oxidation. These strategies are scrutinized in four main categories, namely storage conditions, emulsifiers, optimization of production methods, and antioxidants. Afterward, oxidation in all types of emulsions, including conventional ones (oil-in-water and water-in-oil) and uncommon emulsions in food production (oil-in-oil), is reviewed. Furthermore, the oxidation and oxidative stability of multiple emulsions, nanoemulsions, and Pickering emulsions are taken into account. Finally, oxidative processes across different parent and food emulsions were explained taking a comparative approach.
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Lípidos , Agua , Emulsiones , Oxidación-Reducción , Estrés OxidativoRESUMEN
Distributed acoustic sensors (DAS) perform distributed and dynamic strain or temperature change measurements by comparing a measured time-domain trace with a previous fiber reference state. Large strain or temperature fluctuations or laser frequency noise impose the need to update such a reference, making it necessary to integrate the short-term variation measurements if absolute strain or temperature variations are to be obtained. This has the drawback of introducing a 1/f noise component, as noise is integrated with each cumulative variation measurement, which is detrimental to the determination of very slow processes (i.e., in the mHz frequency range or below). This work analyzes the long-term stability of chirped-pulse phase-sensitive optical time-domain reflectometry (CP-ΦOTDR) with multi-frequency database demodulation (MFDD) to carry out "calibrated" measurements in a DAS along an unmodified SMF. It is shown that, under the conditions studied in this work, a "calibrated" chirped-pulse DAS (CP-DAS) with a completely suppressed reference update-induced 1/f noise component is achieved capable of making measurements over periods of more than 2 months with the same set of references, even when switching off the interrogator during the measurement.
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PURPOSE OF REVIEW: To review the current evidence for coronary revascularization in patients with diabetes mellitus (DM) in the setting of an acute coronary syndrome (ACS). RECENT FINDINGS: In patients with DM and stable multivessel ischemic heart disease, coronary artery bypass graft surgery (CABG) has been observed to be superior to percutaneous coronary intervention (PCI) in long-term follow-up, leading to lower rates of all-cause mortality, myocardial infarction, and repeat revascularization. In the ACS setting, PCI remains the most frequently performed procedure. In patients with an ST-segment-elevation myocardial infarction (STEMI), primary PCI should be the revascularization method of choice, whenever feasible. Controversy still exists regarding when and how to deal with possible residual lesions. In the non-ST-segment-elevation (NSTE) ACS setting, although there are no data from randomized controlled trials (RCTs), recent observational data and sub-analyses of randomized studies have suggested that CABG may be the preferred approach for patients with DM and multivessel coronary disease. There is a paucity of RCTs evaluating revascularization strategies (PCI and CABG) in patients with DM and ACS. CABG may be a viable strategy, leading to improved outcomes, especially following NSTE-ACS.
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Síndrome Coronario Agudo , Enfermedad de la Arteria Coronaria , Diabetes Mellitus , Infarto del Miocardio , Intervención Coronaria Percutánea , Síndrome Coronario Agudo/cirugía , Puente de Arteria Coronaria/métodos , Enfermedad de la Arteria Coronaria/cirugía , Humanos , Infarto del Miocardio/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: Implicit cognition has been linked to relapse in substance use disorder (SUD). Studies on attentional bias have found different outcomes related to the therapeutic context, finding an association with relapse in inpatients but not in outpatients. There are no similar studies that use associations in semantic memory as a measure of implicit cognition. OBJECTIVES: (i) to analyze the relationship between a measure of associations in semantic memory and relapse in inpatients and outpatients; (ii) to compare the evolution of these associations between inpatients and outpatients after 3 months of treatment. METHODS: Eighty nine outpatients and 94 inpatients with SUD for cocaine and alcohol participated in this study. We employed a longitudinal design with a baseline evaluation and follow-up after three months, using the Word Association Task for Drug Use Disorder (WAT-DUD). RESULTS: The choice of drug-related words predicted relapse in cocaine (odds ratio = 1.97, z = 2.01, p = .045) and alcohol-cocaine (odds ratio = 2.39, z = 2.55, p = .011) use. Follow-up at 3 months revealed a reduction in the choice of drug-related words in inpatients (Z = 2.031, p = .042). CONCLUSIONS: A greater choice of drug-associated words in the presence of ambiguous images was related to relapse in inpatients but not in outpatients. The inpatients group showed a reduction in the semantic association with drugs during the first three months of treatment.
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Cocaína , Trastornos Relacionados con Sustancias , Cognición , Humanos , Memoria , Recurrencia , Trastornos Relacionados con Sustancias/terapiaRESUMEN
OBJECTIVES: We aimed to evaluate the early and one-year outcomes of Impella-supported high-risk nonemergent percutaneous coronary intervention (PCI). BACKGROUND: The evidence for the use of mechanical circulatory support (MCS) devices in high-risk nonemergent PCI is limited and nonconclusive. METHODS: We performed a single-center retrospective study including all patients who underwent high-risk nonemergent PCI supported by Impella 2.5/CP at our institution between January 2009 and June 2018. This patient population was propensity score matched with subjects undergoing PCI with no MCS. The primary endpoint was major adverse cardiac events (MACE: all-cause death, myocardial infarction [MI], and target lesion revascularization) at one-year follow-up. RESULTS: Two-hundred fifty patients undergoing Impella-supported nonemergent PCI were matched to 250 controls. The two groups were well balanced in terms of clinical and angiographic characteristics. Left main PCI was performed more frequently among Impella-supported patients (26% vs. 11%, p < .001), who also had numerically higher prevalence of rotational atherectomy use (44% vs. 37%, p = .10) and a higher number of vessels treated (1.8 ± 0.8 vs. 1.3 ± 0.6, p < .001), compared with controls. Impella-supported patients suffered a higher incidence of periprocedural MI (14.0% vs. 6.4%, p = .005), major bleeding (6.8% vs. 2.8%, p = .04), and need for blood transfusions (11.2% vs. 4.8%, p = .008). However, at one-year follow-up there were no differences in the rates of MACE (31.2% vs. 27.4%, p = .78) or any of its individual components between Impella-supported patients and controls. CONCLUSIONS: Although Impella-supported patients suffer a higher incidence of periprocedural adverse events (partially linked to more aggressive PCI), the incidence of one-year MACE was similar between the Impella and control group.
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Enfermedad de la Arteria Coronaria , Corazón Auxiliar , Intervención Coronaria Percutánea , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/cirugía , Corazón Auxiliar/efectos adversos , Humanos , Intervención Coronaria Percutánea/efectos adversos , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: Hybrid PET/MR imaging has significant potential in cardiology due to its combination of molecular PET imaging and cardiac MR. Multi-tissue-class MR-based attenuation correction (MRAC) is necessary for accurate PET quantification. Moreover, for thoracic PET imaging, respiration is known to lead to misalignments of MRAC and PET data that result in PET artifacts. These factors can be addressed by using multi-echo MR for tissue segmentation and motion-robust or motion-gated acquisitions. However, the combination of these strategies is not routinely available and can be prone to errors. In this study, we examine the qualitative and quantitative impacts of multi-class MRAC compared to a more widely available simple two-class MRAC for cardiac PET/MR. METHODS AND RESULTS: In a cohort of patients with cardiac sarcoidosis, we acquired MRAC data using multi-echo radial gradient-echo MR imaging. Water-fat separation was used to produce attenuation maps with up to 4 tissue classes including water-based soft tissue, fat, lung, and background air. Simultaneously acquired 18F-fluorodeoxyglucose PET data were subsequently reconstructed using each attenuation map separately. PET uptake values were measured in the myocardium and compared between different PET images. The inclusion of lung and subcutaneous fat in the MRAC maps significantly affected the quantification of 18F-fluorodeoxyglucose activity in the myocardium but only moderately altered the appearance of the PET image without introduction of image artifacts. CONCLUSION: Optimal MRAC for cardiac PET/MR applications should include segmentation of all tissues in combination with compensation for the respiratory-related motion of the heart. Simple two-class MRAC is adequate for qualitative clinical assessment.
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Corazón/diagnóstico por imagen , Angiografía por Resonancia Magnética/normas , Tomografía Computarizada por Tomografía de Emisión de Positrones/normas , Anciano , Estudios de Cohortes , Femenino , Fluorodesoxiglucosa F18/administración & dosificación , Fluorodesoxiglucosa F18/uso terapéutico , Corazón/fisiopatología , Humanos , Angiografía por Resonancia Magnética/métodos , Angiografía por Resonancia Magnética/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones/estadística & datos numéricos , Radiofármacos/administración & dosificación , Radiofármacos/uso terapéuticoRESUMEN
PURPOSE: Patients evaluated in the emergency department (ED) who have concerning symptoms suggestive of a cancer diagnosis are mostly referred to the quick diagnosis unit of our tertiary hospital. This study analyzed the impact of the Covid-19 pandemic on the volume, disease patterns, and accessibility to essential investigations of patients with suspected cancer referred by the ED to this unit. METHODS: Trends in referrals were analyzed from January 1 to July 8, 2020 and the corresponding dates of 2019. Only non-Covid-19 conditions were evaluated. Three time-based cohorts were defined: prepandemic (January 1-February 19), pandemic (February 19-April 22), and postpandemic (April 22-July 8). Along with descriptive statistics, linear regression was used to test for time trends with weekly referrals as the dependent variable. RESULTS: There were 384, 193, and 450 patients referred during the prepandemic, pandemic, and postpandemic periods, respectively. Following an increasing rate, referrals decreased to unprecedented levels in the pandemic period (average weekly slope: -2.1 cases), then increasing again until near normalization. Waiting times to most diagnostic procedures including radiology, endoscopic, nuclear medicine, and biopsy/cytology during the pandemic period were significantly delayed and time-to-diagnosis was considerably longer (19.72 ± 10.37 days vs. 8.33 ± 3.94 days in prepandemic and 13.49 ± 6.45 days in postpandemic period; P < 0.001 in both). Compared to other cohorts, pandemic cohort patients were more likely to have unintentional weight loss and fever of unknown origin as referral indications while anemia and lymphadenopathy were less common. Patients from the pandemic cohort had a significantly lower rate of malignancies and higher of benign gastrointestinal disorders (40.93% vs. 19.53% and 20.89% in prepandemic and postpandemic periods, respectively; P < 0.001 in both), most notably irritable bowel disease, and of mental and behavioral disorders (15.54% vs. 3.39% and 6.00% in prepandemic and postpandemic periods, respectively; P < 0.001 in both). CONCLUSIONS: As our hospital switched its traditional care to one focused on Covid-19 patients, recognized indicators of healthcare quality of quick diagnosis units were severely disrupted. The clinical patterns of presentation and diagnosis of the pandemic period suggested that mass media-generated mental and behavioral responses with distressing symptoms played a significant role in most of these patients.
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COVID-19/prevención & control , Servicio de Urgencia en Hospital/tendencias , Accesibilidad a los Servicios de Salud/tendencias , Neoplasias/diagnóstico , Unidades de Diagnóstico Rápido/tendencias , Derivación y Consulta/tendencias , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Diagnóstico Tardío/tendencias , Diagnóstico Diferencial , Servicio de Urgencia en Hospital/organización & administración , Femenino , Estudios de Seguimiento , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Estudios Retrospectivos , España , Centros de Atención Terciaria , Adulto JovenRESUMEN
OBJECTIVE: The purpose of this systematic review was to examine the evidence for impaired executive functioning in patients diagnosed with a dual pathology of personality disorder (PD) and substance use disorder, and to identify whether differences exist in comparison to those with a single diagnosis. Methods: A systematic search was conducted to identify studies using measures of executive functioning in patients with PD-substance use disorder dual pathology. Sixteen studies were selected. Results: The results indicate that dual pathology patients with Cluster C personality disorder do not differ from controls, and that the presence of dual pathology does not influence the updating domain of executive functioning. The findings were inconclusive with regard to dual pathology patients with Cluster B personality disorders. Whilst the various studies consistently show that these patients show worse performance than the control groups, here are contradictory results with regard to whether Cluster B personality disorders add more alterations in executive functioning to those that already appear in substance use disorder. Conclusions: The results suggest the need for further research that more adequately controls variables such as time in treatment, medication, and sample size, whilst there is also a need to employ longitudinal designs that include more patients from Clusters A and C.
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Trastornos de la Personalidad , Trastornos Relacionados con Sustancias , Función Ejecutiva , Humanos , Trastornos de la Personalidad/complicaciones , Trastornos de la Personalidad/epidemiología , Trastornos Relacionados con Sustancias/complicaciones , Trastornos Relacionados con Sustancias/epidemiologíaRESUMEN
OBJECTIVES: Statins are the cornerstone of the treatment and prevention of cardiovascular disease but have been associated with muscular side effects, among others. If patients are not properly evaluated, statin discontinuation may take place, leaving patients' symptoms unresolved and precluding an effective cardiovascular treatment. The present study aims to describe the clinical characteristics, the diagnostic process and the final diagnosis of selected patients with suspected statin-induced myopathy, with quite different alternative diagnoses. METHODS: Among the 86 patients referred to our unit for evaluation since 2012, 6 patients with suspected statin-induced myopathy that was finally ruled out were selected as examples because of their illustrative value. All patients were evaluated in a Muscular Diseases Unit by myology experts, and additional testing was performed according to clinical suspicion. RESULTS: Of the six selected patients with suspected statin-induced myopathy, three had a neurogenic aetiology, two had vacuolar myopathies and one had severe hypothyroidism. Statins were permanently discontinued in two cases, with the treatment of one of the latter patients being continued with a protein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. CONCLUSION: Not all patients taking statins who develop muscle complaints have statin-related myopathy. A thorough clinical evaluation and appropriate testing is warranted to avoid an unnecessary increase in cardiovascular risk.
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Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Enfermedades Musculares/inducido químicamente , Anciano , Femenino , Humanos , MasculinoRESUMEN
PURPOSE: Our study investigated the impact of coronary artery calcification (CAC) and systemic inflammation on risks for major adverse cardiovascular events (MACE) following percutaneous coronary intervention (PCI). BACKGROUND: CAC and systemic inflammation are known to be associated with an increased risk of cardiovascular events. METHODS: A total of 17,711 consecutive patients who underwent PCI in our hospital between January 1, 2009 and December 31, 2015 were categorized according to the degree of CAC (moderate/severe vs. none/mild) and high-sensitivity C-reactive protein (hsCRP) level (≥2 vs. <2 mg/L). MACE was defined as death, myocardial infarction (MI), or target vessel revascularization (TVR) occurring over 1 year. RESULTS: Within the four groups, patients with both moderate/severe CAC and elevated hsCRP (n = 1,814 [10.2%]) were older with more comorbid risk factors compared to those with moderate/severe CAC alone (n = 1,687 [9.5%]), elevated hsCRP alone (n = 7,597 [42.9%]) or neither abnormality (n = 6,613 [37.3%]). The analogous 1-year MACE rates were 21.2, 14.9, 11.5, and 7.8%, respectively (p-trend < .001). Results were unchanged after multivariable adjustment, suggesting synergistic adverse effects in patients with both CAC and elevated hsCRP. CONCLUSIONS: The presence of both moderate/severe CAC and systemic inflammation confers a synergistic effect on risk for MACE following PCI, indicating the need for novel or more intense therapeutic interventions to mitigate risk in such patients.
Asunto(s)
Enfermedad de la Arteria Coronaria/terapia , Inflamación/complicaciones , Infarto del Miocardio/etiología , Intervención Coronaria Percutánea/efectos adversos , Calcificación Vascular/terapia , Anciano , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/mortalidad , Bases de Datos Factuales , Femenino , Humanos , Inflamación/sangre , Inflamación/diagnóstico , Inflamación/mortalidad , Mediadores de Inflamación/sangre , Masculino , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/mortalidad , Ciudad de Nueva York , Sistema de Registros , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Calcificación Vascular/complicaciones , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/mortalidadRESUMEN
BACKGROUND: In patients treated with bare metal stents and first-generation drug-eluting stents (DES) smaller stent diameter (SD) has been associated with worse long term outcomes after percutaneous coronary intervention (PCI). Data on the impact of small SD on outcomes after PCI with second-generation DES is scarce. METHODS: Consecutive patients treated with second-generation DES between 2010 and 2016 were included in a single tertiary center. Patients were grouped according to SD: ≤2.50 mm, 2.75 ≤ 3.00 mm, 3.25 ≤ 3.50 mm, and >3.50 mm. One-year event rates were estimated using the Kaplan-Meier method and adjusted hazard ratios were generated using Cox regression analysis. The primary endpoint was major adverse cardiac events (MACE; death, myocardial infarction [MI], or target vessel revascularization [TVR]). RESULTS: Of the 17,607 patients who underwent PCI with second-generation DES, 32.6% (n = 5,741) had SD ≤2.5 mm, 39.1% (n = 6,890) had SD 2.75 ≤ 3.0 mm, 22.2% (n = 3,910) had SD 3.25 ≤ 3.5 mm, and 6.1% (n = 1,066) had SD >3.5 mm. At 1 year, MACE rates were 10.5%, 9.5%, 8.0%, and 8.0%, respectively, with increasing SD (p = .006). TVR rates decreased with increasing SD (7.2%, 5.8%, 4.7%, and 3.3%, respectively [p < .0001]) whereas rates of MI across SD groups were comparable (1.7%, 1.9%, 2.0%, and 1.5%, respectively [p = .60]). After multivariable adjustment, smaller SD remained associated with higher rates of MACE, TVR, and target lesion revascularization. CONCLUSION: In a large cohort of patients undergoing PCI with second-generation DES, smaller SD was associated with increased MACE, driven by higher rates of repeat revascularization. Further research into the optimal treatment of small coronary arteries is warranted.