Extracellular vesicle transfer of lncRNA H19 splice variants to cardiac cells.

The delivery of therapeutic long non-coding RNAs (lncRNA) to the heart by extracellular vesicles (EVs) is promising for heart repair. H19, a lncRNA acting as a major regulator of gene expression within the cardiovascular system, is alternatively spliced, but the loading of its different splice variants into EVs and their subsequent uptake by recipient cardiac cells remain elusive. Here, we dissected the cellular expression of H19 splice variants and their loading into EVs secreted by Wharton-Jelly mesenchymal stromal/stem cells (WJ-MSCs). We demonstrated that overexpression of the mouse H19 gene in WJ-MSCs induces the expression of H19 splice variants at different levels. Interestingly, EVs isolated from the H19-transfected WJ-MSCs (EV-H19) showed similar expression levels for all tested splice variant sets. In vitro, we further demonstrated that EV-H19 was taken up by cardiomyocytes, fibroblasts, and endothelial cells (ECs). Finally, analysis of EV tropism in living rat myocardial slices indicated that EVs were internalized mostly by cardiomyocytes and ECs. Collectively, our results indicated that EVs can be loaded with different lncRNA splice variants and successfully internalized by cardiac cells.

A new formula proposal for placing pH-impedance catheters in pediatric patients.

INTRODUCTION: Esophageal pH-impedance monitoring is a tool for diagnosing gastroesophageal reflux in children. The position of the pH catheter is essential for a reliable reading and the current formulas for calculating catheter insertion length are not completely accurate. The aim of the present study was to develop a new formula for adequate insertion of the pH catheter. MATERIAL AND METHODS: A cross-sectional study was conducted on children that underwent pH-impedance monitoring and later radiographic control, to calculate the correct catheter insertion length. The documented variables were age, sex, weight, height, naris to tragus distance, tragus to sternal notch distance, sternal notch to xiphoid process distance, and initial insertion length determined by the Strobel and height interval formulas. A multivariate regression analysis was carried out to predict the final insertion length. Regression ANOVA and Pearson's adjusted R-squared tests were performed. RESULTS: Forty-five pH-impedance studies were carried out, 53% of which were in males. The age and weight variables were not normally distributed. In the initial regression model, the variables that did not significantly correlate with the final insertion length were: sex (P 0.124), length determined by the Strobel or height interval formulas (P 0.078), naris to tragus distance (P 0.905), and tragus to sternal notch distance (P 0.404). The final equation: 5.6 + (height in cm * 0.12) + (sternal notch to xiphoid process distance * 0.57) produced an R2 of 0.93 (P 0.000). CONCLUSIONS: This formula can be considered a valid option for placement of the pH-impedance monitoring catheter in pediatrics.

A comparison of endoscopic procedures performed at a tertiary care hospital before and during the SARS-CoV-2 pandemic.

INTRODUCTION AND AIM: SARS-CoV-2 emerged in 2019 and had a huge impact on the world. The area of endoscopy suffered great changes, causing a reduction in the number of procedures and its indications. The aim of our study was to compare the quantity, indication, and type of procedures in 2019 with those in 2020. METHOD: A retrospective, observational, analytic, and cross-sectional study was conducted, obtaining information from the endoscopy registry. The STROBE checklist was employed. STATISTICAL ANALYSIS: The quantitative variables were analyzed with descriptive statistics (measures of central tendency and dispersion) and the categorical variables with frequencies and percentages. The quantitative variables were compared, using the Student's t test/Mann-Whitney U test, and the categorical variables with contingency tables, using the Fisher's exact test. RESULTS: In 2019, a total of 277 procedures were performed, compared with 139 in 2020. Mean patient age was 98.53 months (61.46 SD) in 2019 and 77.02 months (59.81 SD) in 2020; 352 diagnostic procedures and 136 therapeutic procedures were carried out in 2019, compared with 51 diagnostic procedures and 88 therapeutic procedures in 2020. The number of diagnostic and therapeutic procedures were inverted (72.1%-36.7% and 27.9%-63.3%, respectively) (p<0.0001). Esophageal varices, upper gastrointestinal bleeding (UGIB), and foreign body extraction were the indications, in order of predominance in 2019, compared with foreign body extraction (p<0.05), UGIB, and esophageal varices in 2020. There were no differences regarding colonoscopy. CONCLUSION: There was a clear difference in indication and type of procedure, with an increase in foreign body extraction in preschoolers.

Optimization of a new liquid scintillation spectrometer for the measurement of environmental levels of 3H in water samples.

The activity concentration of 3H in water samples collected from places unaffected by nuclear activities or for human consumption can be very low. In these cases, determination procedures must achieve a Minimum Detectable Activity (MDA) low enough to ensure that 3H is accurately determined. In this paper, we present a method that uses a new Liquid Scintillation Spectrometer (LSC in what follows): the Quantulus GCT 6220. Furthermore, a new liquid scintillation cocktail, the ProSafe LT+, has been tested for 3H measurement, showing to be a good option for the determination of low levels of this radionuclide. The MDAs achieved are low enough to enable the measurement of very low levels of 3H in recent environmental water. The results obtained using a Quantulus GCT 6220 and Prosafe LT + are compared to those obtained with a Quantulus 1220 and Prosafe HC + as liquid scintillation cocktail.

Approach to non-compressive myeloneuropathy through a rendezvous of 11 cases from an Indian backdrop.

Introduction: Myeloneuropathy is a diagnosis ascribed to disorders that concomitantly affect the spinal cord and peripheral nerves. Recognizing this syndrome may sometimes be arduous, even for the most consummate clinicians, because symptomatology can mimic either spinal cord or peripheral nerve disease. Besides, examination findings suggest a predominantly myelopathic or neuropathic picture. This article reports a rendezvous of rare cases of clinically diagnosed myeloneuropathy with different etiological backgrounds and therapeutic responses. Methods: Eleven cases of non-compressive myeloneuropathy were admitted to the Department of General Medicine of Burdwan Medical College and Hospital, Burdwan, West Bengal, India, between May 2018 and May 2022. Results: We report the cases of 11 patients (6 men and 5 women) who presented with myeloneuropathy of different etiologies (vitamin B12, copper, and vitamin E deficiencies, organophosphate poisoning, chronic alcohol abuse, illicit substances abuse, anti-thyroid peroxidase/anti-thyroglobulin antibody-related neurologic disorder responsive to steroids, Sjögren syndrome, chikungunya infection, paraneoplastic, and hereditary). Conclusion: Meticulous historical analysis, careful clinical examination, and apposite utilization and interpretation of biochemical, electrophysiological, and neuroimaging findings are sine-qua-non for an accurate and consistent approach to evaluating a suspected case of myeloneuropathy, facilitating early treatment and recovery. Differential identification of these disorders needs an in-depth perception of the mode of onset of symptoms, the course of progression of the disease, the pattern of myelopathic/neuropathic findings, and recognition of other neurological or systemic manifestations. For untroubled understanding, etiologies of myeloneuropathies should be subdivided into a few broad categories, e.g., metabolic (nutritional), toxic (toxin-induced), infectious, inflammatory (immune-mediated), paraneoplastic, and hereditary disorders.

Introducción: La mieloneuropatía es un síndrome que afecta concomitantemente la médula espinal y los nervios periféricos. Reconocerlo a veces puede ser arduo, incluso para los médicos más experimentados, porque la sintomatología puede simular una enfermedad de la médula espinal o de los nervios periféricos. Además, los hallazgos del examen sugieren un cuadro predominantemente mielopático o neuropático. Este artículo describe una serie de casos raros de mieloneuropatía de distintas causas y con respuestas terapéuticas distintas. Métodos: Once casos de mieloneuropatía no compresiva fueron ingresados en el Departamento de Medicina General del Burdwan Medical College, and Hospital, Burdwan, Bengala Occidental, India, entre mayo de 2018 y mayo de 2022. Resultados: Presentamos 11 pacientes (seis hombres y cinco mujeres) con mieloneuropatía de diferentes etiologías (deficiencias de vitamina B12, cobre y vitamina E, intoxicación por organofosforados, abuso crónico de alcohol, abuso de sustancias ilícitas, trastorno neurológico relacionado con anticuerpos anti-tiroglobulina / antiperoxidasa tiroidea que responde a esteroides, síndrome de Sjögren, infección por chikungunya, paraneoplásico y hereditario). Conclusión: El análisis meticuloso de la historia y del examen clínico, así como la utilización e interpretación adecuadas de los hallazgos bioquímicos, electrofisiológicos y de neuroimagen son condiciones sine qua non para un enfoque preciso y consistente para evaluar un caso sospechoso de mieloneuropatía, lo que facilita el tratamiento temprano y su recuperación. El diagnóstico diferencial de esta patología requiere un conocimiento del modo de inicio de los síntomas, su progresión, el patrón de hallazgos mielopáticos/neuropáticos y el reconocimiento de otras manifestaciones neurológicas o sistémicas. Las etiologías de las mieloneuropatías deben subdividirse en trastornos metabólicos (nutricionales), tóxicos (inducidos por toxinas), infecciosos, inflamatorios (mediados por mecanismos inmunitarios), paraneoplásicos y hereditarias.

Etiological spectrum and diagnostic challenges of short-duration fever in West Bengal (India). A cross-sectional tertiary care study.

INTRODUCTION: The scarcity of epidemiological data on acute febrile illnesses from South Asia impairs evidence-based clinical decision-making. Our study aimed to explore the etiological spectrum of short-duration fever in patients admitted to a tertiary care hospital in West Bengal, India. METHODS: We conducted a cross-sectional study from May 2021 to April 2022 involving 150 adult patients presenting with a fever lasting less than two weeks at Burdwan Medical College and Hospital (West Bengal, India). We performed comprehensive clinical assessments, including microbiological, serological, and other specific investigations, to identify the causes of the fever. RESULTS: The demographic profile predominantly included individuals aged 21-40 years, with a male-to-female ratio of 1.9:1; 60.7% of participants were from rural areas. The primary etiological agents identified were scrub typhus (25.3%), dengue (15.3%), and enteric fever (13.3%). Notably, 80% of patients presented with non-localizing symptoms, while 14.7% had respiratory symptoms. Blood cultures pinpointed Salmonella typhi and Staphylococcus aureus in a minority of cases (3.3%); malaria, primarily Plasmodium vivax, was diagnosed in 12% of the cases. CONCLUSION: Our findings highlight the complexity of diagnosing short-duration fevers, dominated by a wide range of etiological agents, with a notable prevalence of scrub typhus. These results underscore the urgent need for enhanced diagnostic facilities, including the availability of scrub typhus testing at primary healthcare centers. We recommend empirical doxycycline therapy for suspected cases and emphasize the need for further research to develop management guidelines for acute febrile illnesses. This study also highlights the importance of raising both community and clinician awareness to prevent irrational antibiotic use.

Monitorización ambulatoria de la presión arterial en adultos y población pediátrica. Una revisión narrativa / Ambulatory blood pressure monitoring, adult and pediatric population. A narrative review

La hipertensión arterial (HTA) se ha convertido en un factor de riesgo central para el desarrollo de enfermedades cardiovasculares (CV), lo que subraya la importancia de su diagnóstico preciso. Numerosos estudios han establecido una estrecha relación entre los valores elevados de la presión arterial sistólica (PAS) y diastólica (PAD) y un incremento en el riesgo de padecer algún evento cardiovascular (ECV). Tradicionalmente, las mediciones de la presión arterial (PA) realizadas en entornos clínicos han sido el principal método para diagnosticar y evaluar la HTA. No obstante, en los últimos años, se ha reconocido que las mediciones de la PA obtenidas fuera del ambiente clínico, mediante la automedida de la presión arterial (AMPA) y la monitorización ambulatoria de la presión arterial (MAPA), ofrecen una perspectiva más realista de la vida cotidiana de los pacientes y, por lo tanto, brindan resultados más fiables. Dada la evolución de los dispositivos médicos, los criterios diagnósticos y la creciente relevancia de componentes de la MAPA en la predicción de ECV, se requiere una actualización integral que sea práctica para la clínica. Esta revisión tiene como objetivo proporcionar una actualización de la MAPA, enfocándose en su importancia en la evaluación de la HTA. Además, se analizarán los umbrales diagnósticos, los distintos fenotipos según el ciclo circadiano y las recomendaciones en diferentes poblaciones, asimismo, se ofrecerán sugerencias concretas para la implementación efectiva de la MAPA en la práctica clínica, lo que permitirá a los profesionales de la salud tomar decisiones fundamentadas y mejorar la atención de sus pacientes.(AU)

Hypertension has become a central risk factor for the development of cardiovascular disease, underscoring the importance of its accurate diagnosis. Numerous studies have established a close relationship between elevated systolic (SBP) and diastolic (DBP) blood pressure and an increased risk of cardiovascular event (CVE). Traditionally, blood pressure (BP) measurements performed in clinical settings have been the main method for diagnosing and assessing hypertension. However, in recent years, it has been recognized that BP measurements obtained outside the clinical setting, using self-monitoring blood pressure (SMBP) and ambulatory blood pressure monitoring (ABPM), offer a more realistic perspective of patients’ daily lives and therefore provide more reliable results. Given the evolution of medical devices, diagnostic criteria, and the increasing relevance of certain components of ABPM in the prediction of adverse cardiovascular outcomes, a comprehensive update that is practical for daily clinical practice is required. The main objective of this article is to provide an updated review of ABPM, focusing on its importance in the evaluation of hypertension and its impact on public health in Colombia. In addition, it will discuss the implications of changes in diagnostic thresholds and provide concrete recommendations for the effective implementation of ABPM in clinical practice, allowing health professionals to make informed decisions and improve the care of their patients.(AU)

Regional Distribution of Extracellular Volume Quantified by Cardiac CT in Aortic Stenosis: Insights Into Disease Mechanisms and Impact on Outcomes.

BACKGROUND: Extracellular volume fraction (ECV) is a marker for myocardial fibrosis and infiltration, can be quantified using cardiac computed tomography (ECVCT), and has prognostic utility in several diseases. This study aims to map out regional differences in ECVCT to obtain greater insights into the pathophysiological mechanisms of ECV expansion and its clinical implications. METHODS: Three prospective cohorts were included: patients with aortic stenosis (AS) and coexisting AS and transthyretin cardiac amyloidosis were referred for a transcatheter aortic valve replacement and had ECG-gated CT angiography and Technetium-99m-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy to differentiate between the 2 cohorts. Controls had CT angiography and cardiac magnetic resonance demonstrating no significant coronary artery disease or infarction. Global and regional ECVCT was analyzed, and its association with mortality was assessed for patients with AS. RESULTS: In 199 patients, controls (n=65; 66% male), AS (n=115), and coexisting AS and transthyretin cardiac amyloidosis (n=19) had a global ECVCT of 26.1 (25.0-27.8%) versus 29.1 (27.5-31.1%) versus 37.4 (32.5-46.6%), respectively; P<0.001. Across cohorts, ECVCT was higher at the base (versus apex), the inferoseptum (versus anterolateral wall), and the subendocardium (versus subepicardium); P<0.05 for all. Among patients with AS, epicardial ECVCT, rather than any other regional value or global ECVCT, was the strongest predictor of mortality at a median of 3.9 (max 6.3) years (adjusted hazard ratio, 1.21 [95% CI, 1.08-1.36]; P=0.002). CONCLUSIONS: Regional differences in ECVCT suggest a predilection for fibrosis and amyloid infiltration at the base, subendocardium, inferior wall, and septum more than the anterior and lateral myocardium. ECVCT can predict long-term mortality with the subepicardium demonstrating the strongest discriminatory power. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03029026 and NCT03094143.

Unveiling cellular and molecular aspects of ascending thoracic aortic aneurysms and dissections.

Ascending thoracic aortic aneurysm (ATAA) remains a significant medical concern, with its asymptomatic nature posing diagnostic and monitoring challenges, thereby increasing the risk of aortic wall dissection and rupture. Current management of aortic repair relies on an aortic diameter threshold. However, this approach underestimates the complexity of aortic wall disease due to important knowledge gaps in understanding its underlying pathologic mechanisms.Since traditional risk factors cannot explain the initiation and progression of ATAA leading to dissection, local vascular factors such as extracellular matrix (ECM) and vascular smooth muscle cells (VSMCs) might harbor targets for early diagnosis and intervention. Derived from diverse embryonic lineages, VSMCs exhibit varied responses to genetic abnormalities that regulate their contractility. The transition of VSMCs into different phenotypes is an adaptive response to stress stimuli such as hemodynamic changes resulting from cardiovascular disease, aging, lifestyle, and genetic predisposition. Upon longer exposure to stress stimuli, VSMC phenotypic switching can instigate pathologic remodeling that contributes to the pathogenesis of ATAA.This review aims to illuminate the current understanding of cellular and molecular characteristics associated with ATAA and dissection, emphasizing the need for a more nuanced comprehension of the impaired ECM-VSMC network.

Aplicación clinicorradiológica del uso de la tomografía computarizada craneal de tecnología espectral en el manejo del ictus isquémico agudo tras trombectomía mecánica / Clinicoradiological application of the use of spectral cranial computed tomography in the management of acute ischemic stroke after mechanical thrombectomy

Introducción El ictus isquémico agudo es una de las principales causas globales de morbimortalidad. La trombectomía mecánica ha mejorado el pronóstico funcional de esta patología; sin embargo, la transformación hemorrágica es una complicación frecuente. La tomografía computarizada (TC) de tecnología espectral, como prueba de neuroimagen de control, diferencia la extravasación de contraste de la transformación hemorrágica gracias al diferente comportamiento de los materiales a la energía dual, y esta distinción es de utilidad en su manejo clinicoterapéutico. Material y métodos. Estudio unicéntrico, observacional y retrospectivo, en el cual se investigó, mediante el acceso a una base de datos disociada y a la historia clínica, la presencia de una serie de variables clínicas, radiológicas y terapéuticas en los pacientes con ictus isquémico agudo que fueron tratados con trombectomía mecánica en nuestro hospital entre julio de 2022 y marzo de 2023.ResultadosDe los 155 pacientes incluidos, se realizó una TC craneal espectral en 63 y convencional en 75. En el grupo de TC espectral se detectaron 21 imágenes hiperdensas y en el grupo de TC convencional fueron 28. En el 42,8% de los casos en los que se detectó una hiperdensidad en el grupo de TC convencional no se pudo distinguir entre extravasación de contraste y transformación hemorrágica, en comparación con el 4,8% del grupo de TC espectral (p < 0,001).ConclusionesLa TC espectral confiere una gran confianza diagnóstica al radiólogo para establecer el tipo de hiperdensidad detectada y, por ello, proporciona también una gran confianza terapéutica al neurólogo para reiniciar precozmente la anticoagulación. (AU)

Introduction. Acute ischemic stroke is one of the leading global causes of morbidity and mortality. Mechanical thrombectomy has improved the functional prognosis of this condition; however, hemorrhagic transformation is a common complication. Spectral computed tomography (CT) imaging, as a neuroimaging control test, distinguishes contrast extravasation from hemorrhagic transformation due to the differential behavior of materials at dual energy levels. This distinction is valuable in its clinical therapeutic management.Material and methods. A single-center, observational, retrospective study was conducted in which the presence of various clinical, radiological, and therapeutic variables in patients with acute ischemic stroke treated with mechanical thrombectomy at our hospital between July 2022 and March 2023 was investigated using access to a dissociated database and medical records.Results. Out of 155 included patients, spectral cranial CT was performed in 63, and conventional cranial CT in 75. In the spectral CT group, 21 hyperdense images were detected, compared to 28 in the conventional CT group. In 42.8% of cases where hyperdensity was detected in the conventional CT group, it was not possible to distinguish between contrast extravasation and hemorrhagic transformation, in contrast to the 4.8% in the spectral CT group (p < 0.001).Conclusions. Spectral CT provides high diagnostic confidence to the radiologist in identifying the type of detected hyperdensity, thereby offering significant therapeutic confidence to the neurologist in early resuming anticoagulation therapy. (AU)

Genomic Engineering of Oral Keratinocytes to Establish In Vitro Oral Potentially Malignant Disease Models as a Platform for Treatment Investigation.

Precancerous cells in the oral cavity may appear as oral potentially malignant disorders, but they may also present as dysplasia without visual manifestation in tumor-adjacent tissue. As it is currently not possible to prevent the malignant transformation of these oral precancers, new treatments are urgently awaited. Here, we generated precancer culture models using a previously established method for the generation of oral keratinocyte cultures and incorporated CRISPR/Cas9 editing. The generated cell lines were used to investigate the efficacy of a set of small molecule inhibitors. Tumor-adjacent mucosa and oral leukoplakia biopsies were cultured and genetically characterized. Mutations were introduced in CDKN2A and TP53 using CRISPR/Cas9 and combined with the ectopic activation of telomerase to generate cell lines with prolonged proliferation. The method was tested in normal oral keratinocytes and tumor-adjacent biopsies and subsequently applied to a large set of oral leukoplakia biopsies. Finally, a subset of the immortalized cell lines was used to assess the efficacy of a set of small molecule inhibitors. Culturing and genomic engineering was highly efficient for normal and tumor-adjacent oral keratinocytes, but success rates in oral leukoplakia were remarkably low. Knock-out of CDKN2A in combination with either the activation of telomerase or knock-out of TP53 seemed a prerequisite for immortalization. Prolonged culturing was accompanied by additional genetic aberrations in these cultures. The generated cell lines were more sensitive than normal keratinocytes to small molecule inhibitors of previously identified targets. In conclusion, while very effective for normal keratinocytes and tumor-adjacent biopsies, the success rate of oral leukoplakia cell culturing methods was very low. Genomic engineering enabled the prolonged culturing of OL-derived keratinocytes but was associated with acquired genetic changes. Further studies are required to assess to what extent the immortalized cultures faithfully represent characteristics of the cells in vivo.

Clinicoradiological application of the use of spectral cranial computed tomography in the management of acute ischemic stroke after mechanical thrombectomy. / Aplicación clinicorradiológica del uso de la tomografía computarizada craneal de tecnología espectral en el manejo del ictus isquémico agudo tras trombectomía mecánica.

INTRODUCTION: Acute ischemic stroke is one of the leading global causes of morbidity and mortality. Mechanical thrombectomy has improved the functional prognosis of this condition; however, hemorrhagic transformation is a common complication. Spectral computed tomography (CT) imaging, as a neuroimaging control test, distinguishes contrast extravasation from hemorrhagic transformation due to the differential behavior of materials at dual energy levels. This distinction is valuable in its clinical therapeutic management. MATERIAL AND METHODS: A single-center, observational, retrospective study was conducted in which the presence of various clinical, radiological, and therapeutic variables in patients with acute ischemic stroke treated with mechanical thrombectomy at our hospital between July 2022 and March 2023 was investigated using access to a dissociated database and medical records. RESULTS: Out of 155 included patients, spectral cranial CT was performed in 63, and conventional cranial CT in 75. In the spectral CT group, 21 hyperdense images were detected, compared to 28 in the conventional CT group. In 42.8% of cases where hyperdensity was detected in the conventional CT group, it was not possible to distinguish between contrast extravasation and hemorrhagic transformation, in contrast to the 4.8% in the spectral CT group (p < 0.001). CONCLUSIONS: Spectral CT provides high diagnostic confidence to the radiologist in identifying the type of detected hyperdensity, thereby offering significant therapeutic confidence to the neurologist in early resuming anticoagulation therapy.

TITLE: Aplicación clinicorradiológica del uso de la tomografía computarizada craneal de tecnología espectral en el manejo del ictus isquémico agudo tras trombectomía mecánica.Introducción. El ictus isquémico agudo es una de las principales causas globales de morbimortalidad. La trombectomía mecánica ha mejorado el pronóstico funcional de esta patología; sin embargo, la transformación hemorrágica es una complicación frecuente. La tomografía computarizada (TC) de tecnología espectral, como prueba de neuroimagen de control, diferencia la extravasación de contraste de la transformación hemorrágica gracias al diferente comportamiento de los materiales a la energía dual, y esta distinción es de utilidad en su manejo clinicoterapéutico. Material y métodos. Estudio unicéntrico, observacional y retrospectivo, en el cual se investigó, mediante el acceso a una base de datos disociada y a la historia clínica, la presencia de una serie de variables clínicas, radiológicas y terapéuticas en los pacientes con ictus isquémico agudo que fueron tratados con trombectomía mecánica en nuestro hospital entre julio de 2022 y marzo de 2023. Resultados. De los 155 pacientes incluidos, se realizó una TC craneal espectral en 63 y convencional en 75. En el grupo de TC espectral se detectaron 21 imágenes hiperdensas y en el grupo de TC convencional fueron 28. En el 42,8% de los casos en los que se detectó una hiperdensidad en el grupo de TC convencional no se pudo distinguir entre extravasación de contraste y transformación hemorrágica, en comparación con el 4,8% del grupo de TC espectral (p < 0,001). Conclusiones. La TC espectral confiere una gran confianza diagnóstica al radiólogo para establecer el tipo de hiperdensidad detectada y, por ello, proporciona también una gran confianza terapéutica al neurólogo para reiniciar precozmente la anticoagulación.

[Ambulatory blood pressure monitoring, adult and pediatric population. A narrative review]. / Monitorización ambulatoria de la presión arterial en adultos y población pediátrica. Una revisión narrativa.

Hypertension has become a central risk factor for the development of cardiovascular disease, underscoring the importance of its accurate diagnosis. Numerous studies have established a close relationship between elevated systolic (SBP) and diastolic (DBP) blood pressure and an increased risk of cardiovascular event (CVE). Traditionally, blood pressure (BP) measurements performed in clinical settings have been the main method for diagnosing and assessing hypertension. However, in recent years, it has been recognized that BP measurements obtained outside the clinical setting, using self-monitoring blood pressure (SMBP) and ambulatory blood pressure monitoring (ABPM), offer a more realistic perspective of patients' daily lives and therefore provide more reliable results. Given the evolution of medical devices, diagnostic criteria, and the increasing relevance of certain components of ABPM in the prediction of adverse cardiovascular outcomes, a comprehensive update that is practical for daily clinical practice is required. The main objective of this article is to provide an updated review of ABPM, focusing on its importance in the evaluation of hypertension and its impact on public health in Colombia. In addition, it will discuss the implications of changes in diagnostic thresholds and provide concrete recommendations for the effective implementation of ABPM in clinical practice, allowing health professionals to make informed decisions and improve the care of their patients.

Lichen biomonitoring to assess spatial variability, potential sources and human health risks of polycyclic aromatic hydrocarbons (PAHs) and airborne metal concentrations in Manchester (UK).

Airborne metals and organic pollutants are linked to severe human health impacts, i.e. affecting the nervous system and being associated with cancer. Airborne metals and polycyclic aromatic hydrocarbons (PAHs) in urban environments are derived from diverse sources, including combustion and industrial and vehicular emissions, posing a threat to air quality and subsequently human health. A lichen biomonitoring approach was used to assess spatial variability of airborne metals and PAHs, identify potential pollution sources and assess human health risks across the City of Manchester (UK). Metal concentrations recorded in lichen samples were highest within the city centre area and along the major road network, and lichen PAH profiles were dominated by 4-ring PAHs (189.82 ng g-1 in Xanthoria parietina), with 5- and 6-ring PAHs also contributing to the overall PAH profile. Cluster analysis and pollution index factor (PIF) calculations for lichen-derived metal concentrations suggested deteriorated air quality being primarily linked to vehicular emissions. Comparably, PAH diagnostic ratios identified vehicular sources as a primary cause of PAH pollution across Manchester. However, local more complex sources (e.g. industrial emissions) were further identified. Human health risk assessment found a "moderate" risk for adults and children by airborne potential harmful element (PHEs) concentrations, whereas PAH exposure in Manchester is potentially linked to 1455 (ILCR = 1.45 × 10-3) cancer cases (in 1,000,000). Findings of this study indicate that an easy-to-use lichen biomonitoring approach can aid to identify hotspots of impaired air quality and potential human health impacts by airborne metals and PAHs across an urban environment, particularly at locations that are not continuously covered by (non-)automated air quality measurement programmes.

Diagnosis and prognosis of abnormal cardiac scintigraphy uptake suggestive of cardiac amyloidosis using artificial intelligence: a retrospective, international, multicentre, cross-tracer development and validation study.

BACKGROUND: The diagnosis of cardiac amyloidosis can be established non-invasively by scintigraphy using bone-avid tracers, but visual assessment is subjective and can lead to misdiagnosis. We aimed to develop and validate an artificial intelligence (AI) system for standardised and reliable screening of cardiac amyloidosis-suggestive uptake and assess its prognostic value, using a multinational database of 99mTc-scintigraphy data across multiple tracers and scanners. METHODS: In this retrospective, international, multicentre, cross-tracer development and validation study, 16 241 patients with 19 401 scans were included from nine centres: one hospital in Austria (consecutive recruitment Jan 4, 2010, to Aug 19, 2020), five hospital sites in London, UK (consecutive recruitment Oct 1, 2014, to Sept 29, 2022), two centres in China (selected scans from Jan 1, 2021, to Oct 31, 2022), and one centre in Italy (selected scans from Jan 1, 2011, to May 23, 2023). The dataset included all patients referred to whole-body 99mTc-scintigraphy with an anterior view and all 99mTc-labelled tracers currently used to identify cardiac amyloidosis-suggestive uptake. Exclusion criteria were image acquisition at less than 2 h (99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid, 99mTc-hydroxymethylene diphosphonate, and 99mTc-methylene diphosphonate) or less than 1 h (99mTc-pyrophosphate) after tracer injection and if patients' imaging and clinical data could not be linked. Ground truth annotation was derived from centralised core-lab consensus reading of at least three independent experts (CN, TT-W, and JN). An AI system for detection of cardiac amyloidosis-associated high-grade cardiac tracer uptake was developed using data from one centre (Austria) and independently validated in the remaining centres. A multicase, multireader study and a medical algorithmic audit were conducted to assess clinician performance compared with AI and to evaluate and correct failure modes. The system's prognostic value in predicting mortality was tested in the consecutively recruited cohorts using cox proportional hazards models for each cohort individually and for the combined cohorts. FINDINGS: The prevalence of cases positive for cardiac amyloidosis-suggestive uptake was 142 (2%) of 9176 patients in the Austrian, 125 (2%) of 6763 patients in the UK, 63 (62%) of 102 patients in the Chinese, and 103 (52%) of 200 patients in the Italian cohorts. In the Austrian cohort, cross-validation performance showed an area under the curve (AUC) of 1·000 (95% CI 1·000-1·000). Independent validation yielded AUCs of 0·997 (0·993-0·999) for the UK, 0·925 (0·871-0·971) for the Chinese, and 1·000 (0·999-1·000) for the Italian cohorts. In the multicase multireader study, five physicians disagreed in 22 (11%) of 200 cases (Fleiss' kappa 0·89), with a mean AUC of 0·946 (95% CI 0·924-0·967), which was inferior to AI (AUC 0·997 [0·991-1·000], p=0·0040). The medical algorithmic audit demonstrated the system's robustness across demographic factors, tracers, scanners, and centres. The AI's predictions were independently prognostic for overall mortality (adjusted hazard ratio 1·44 [95% CI 1·19-1·74], p<0·0001). INTERPRETATION: AI-based screening of cardiac amyloidosis-suggestive uptake in patients undergoing scintigraphy was reliable, eliminated inter-rater variability, and portended prognostic value, with potential implications for identification, referral, and management pathways. FUNDING: Pfizer.

Fundamental considerations for designing endothelialized in vitro models of thrombosis.

Endothelialized in vitro models for cardiovascular disease have contributed greatly to our current understanding of the complex molecular mechanisms underlying thrombosis. To further elucidate these mechanisms, it is important to consider which fundamental aspects to incorporate into an in vitro model. In this review, we will focus on the design of in vitro endothelialized models of thrombosis. Expanding our understanding of the relation and interplay between the different pathways involved will rely in part on complex models that incorporate endothelial cells, blood, the extracellular matrix, and flow. Importantly, the use of tissue-specific endothelial cells will help in understanding the heterogeneity in thrombotic responses between different vascular beds. The dynamic and complex responses of endothelial cells to different shear rates underlines the importance of incorporating appropriate shear in in vitro models. Alterations in vascular extracellular matrix composition, availability of bioactive molecules, and gradients in concentration and composition of these molecules can all regulate the function of both endothelial cells and perivascular cells. Factors modulating these elements in in vitro models should therefore be considered carefully depending on the research question at hand. As the complexity of in vitro models increases, so can the variability. A bottom-up approach to designing such models will remain an important tool for researchers studying thrombosis. As new techniques are continuously being developed and new pathways are brought to light, research question-dependent considerations will have to be made regarding what aspects of thrombosis to include in in vitro models.

Large animal models of pressure overload-induced cardiac left ventricular hypertrophy to study remodelling of the human heart with aortic stenosis.

Pathologic cardiac hypertrophy is a common consequence of many cardiovascular diseases, including aortic stenosis (AS). AS is known to increase the pressure load of the left ventricle, causing a compensative response of the cardiac muscle, which progressively will lead to dilation and heart failure. At a cellular level, this corresponds to a considerable increase in the size of cardiomyocytes, known as cardiomyocyte hypertrophy, while their proliferation capacity is attenuated upon the first developmental stages. Cardiomyocytes, in order to cope with the increased workload (overload), suffer alterations in their morphology, nuclear content, energy metabolism, intracellular homeostatic mechanisms, contractile activity, and cell death mechanisms. Moreover, modifications in the cardiomyocyte niche, involving inflammation, immune infiltration, fibrosis, and angiogenesis, contribute to the subsequent events of a pathologic hypertrophic response. Considering the emerging need for a better understanding of the condition and treatment improvement, as the only available treatment option of AS consists of surgical interventions at a late stage of the disease, when the cardiac muscle state is irreversible, large animal models have been developed to mimic the human condition, to the greatest extend. Smaller animal models lack physiological, cellular and molecular mechanisms that sufficiently resemblance humans and in vitro techniques yet fail to provide adequate complexity. Animals, such as the ferret (Mustello purtorius furo), lapine (rabbit, Oryctolagus cunigulus), feline (cat, Felis catus), canine (dog, Canis lupus familiaris), ovine (sheep, Ovis aries), and porcine (pig, Sus scrofa), have contributed to research by elucidating implicated cellular and molecular mechanisms of the condition. Essential discoveries of each model are reported and discussed briefly in this review. Results of large animal experimentation could further be interpreted aiming at prevention of the disease progress or, alternatively, at regression of the implicated pathologic mechanisms to a physiologic state. This review summarizes the important aspects of the pathophysiology of LV hypertrophy and the applied surgical large animal models that currently better mimic the condition.

Combined application of high pressure and ultrasound in fig paste: effect on bioactive and volatile compounds.

The combined impact of high-hydrostatic pressure (HHP) and ultrasound (US) on the cyanidin-3-O-rutinoside (C3R), quercetin-3-O-rutinoside (Q3R), and volatile compounds from fig (Ficus carica) paste was investigated. The HHP increased the content of C3R and Q3R, from 70 to 133 mg/kg fw and 31 to 44 mg/kg fw, respectively. The combination of HHP and US further enhanced the extraction of these bioactive compounds. Specifically, processing fig paste with US for 5 min at 40 °C yielded approximately 250 mg of C3R/kg fw and 45 mg of Q3R/kg fw, after 20 min. More than 25 volatile compounds were identified, with benzaldehyde being the predominant compound, accounting > 75%. Trace amounts of hydroxymethylfurfural (< 0.36 mg/100 g fw) were detected in HHP-processed fig paste. The application of HHP at mild temperatures and short time, combined with US, effectively promotes the content of bioactive compounds present in fig paste without adversely affecting the fruit's volatile compounds. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01410-1.