Zurbarán attribution hypothesis supported by pigment analysis and multiband images observation of four paintings by his workshop.

Francisco de Zurbarán was one of the greatest painters of the Spanish Golden Age, with artworks scattered all over the world. Unfortunately, there are hardly any exhaustive studies on the pigments that he used. In this work, four canvas paintings attributed to the Zurbarán Workshop were studied. Each of them presents the figure of a different saint in a particular isolation scene: Saint Bruno, Saint Francis of Assisi, Saint Dominic of Guzman, and Saint Peter Martyr. Nevertheless, the painting of Saint Peter Martyr shows superior quality in both technique and colours, so it is not clear whether this canvas was also made by the Workshop or by Zurbarán himself, as some art historians claim. Coinciding with conservation and restoration works, the paintings were initially analysed with non-invasive techniques such as ultraviolet photography (UV), infrared reflectography (IRR) and X-ray fluorescence (XRF) to determine the characterization of the pigments. Those studies were complemented by stratigraphic analysis of some extracted samples with optical microscopy (OM) and scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX). Among a number of results obtained, we found significant differences between the pigment palette used in Saint Peter Martyr and the other paintings, supporting the hypothesis that this painting was done by Zurbarán himself instead of his workshop. These results could also help to distinguish other authentic paintings by the master's hand from very similar paintings by his workshop or by other artists.

Kummel's disease

Kummel's disease is a crush fracture of a vertebral body caused by a minor trauma, with the most accepted etiology being avascular necrosis. It is more frequent in individuals with risk factors such as osteoporosis or prolonged treatment with corticosteroids. Initially, it usually has normal radiological tests and an asymptomatic period, followed by a progressive onset of pain along with probable kyphosis and a sign of void or fluid abscess on radiological tests, which may create nerve/spinal involvement. The case is presented of a 76-year-old man, who was admitted to this center for the differential diagnosis of a single vertebral lesion. After imaging tests and biopsy, the definitive diagnosis of Kummel's disease was reached. The confirmatory diagnosis was reached by vertebral biopsy, but given its invasive nature, imaging techniques can play a significant role. As regards metabolic imaging tests, bone scintigraphy has shown to be one of the most sensitive tools to detect ischemia in earlier stages or to determine if it affects other locations. The whole body scan with diphosphonates shows an increase in activity in relation to bone remodeling activity in this condition. The 3-phase study makes it possible to differentiate whether it is an acute/subacute or chronic process, and can influence the therapeutic decision. Knowledge of this disease is important to make a differential diagnosis with tumour or infectious pathology, with emphasis on performing imaging tests in the event of persistent pain with a normal initial plaque.

La enfermedad de Kummel es una fractura-aplastamiento de un cuerpo vertebral precedida por un traumatismo menor, cuya etiología más aceptada es la necrosis avascular. Es más frecuente en individuos con factores de riesgo como osteoporosis o tratamiento prolongado con corticoides. Inicialmente, suele presentar pruebas radiológicas normales y un periodo asintomático, con aparición progresiva del dolor junto a probable cifosis y signo del vacío o absceso líquido en las pruebas radiológicas, pudiendo llegar a crear compromiso nervioso/medular. Presentamos el caso de un varón de 76 arios que ingresa en nuestro centro para el diagnóstico diferencial de una lesión única vertebral; tras la realización de las pruebas de imagen y biopsia se llega al diagnóstico definitivo de enfermedad de Kummel. El diagnóstico de confirmación de esta enfermedad se alcanza mediante la biopsia vertebral, pero dada su naturaleza invasiva, las técnicas de imagen toman un papel relevante. En relación con las pruebas de imagen metabólicas, la gammagrafía ósea ha demostrado ser una de las herramientas más sensibles para detectar isquemia en fases más tempranas o para conocer si afecta a otras localizaciones. El rastreo corporal de cuerpo completo con difosfonatos muestra un aumento de actividad en relación con la actividad ósea remodelativa en este cuadro. El estudio de tres fases permite diferenciar si se trata de un proceso agudo/subagudo o crónico, lo que influye en la decisión terapéutica. Es importante el conocimiento de esta enfermedad para realizar diagnóstico diferencial con patología tumoral o infecciosa e insistir en la realización de pruebas de imagen ante la persistencia del dolor con una placa inicial normal.

Role of Isolated Limb Perfusion in the Era of Targeted Therapies and Immunotherapy in Melanoma. A Systematic Review of The Literature.

BACKGROUND: Isolated limb perfusion (ILP) is a locoregional procedure indicated by the unresectable melanoma of the limbs. Its complexity and highly demanding multidisciplinary approach means that it is a technique only implemented in a few referral centers around the globe. This report aims to examine its potential role in the era of targeted therapies and immunotherapy by conducting a systematic review of the literature on ILP. METHODS: PubMed, Embase and Cochrane Library were searched. The eligibility criteria included publications from 2000-2020 providing valid data o effectiveness, survival or toxicity. Studies in which the perfusion methodology was not clearly described, letters to the editor, non-systematic reviews and studies that applied outdated clinical guidelines were excluded. To rule out studies of a low methodological quality and assess the risk of bias, the following aspects were also required: a detailed description of the applied ILP regimen, the clinical context, follow-up periods, analyzed clinical endpoints, and the number of analyzed ILPs. The disagreements were resolved by consensus. The results are presented in tables and figures. RESULTS: Twenty-seven studies including 2637 ILPs were selected. The median overall response rate was 85%, with a median complete response rate of 58.5%. The median overall survival was 38 months, with a 5-year overall survival of 35%. The toxicity was generally mild according to Wieberdink toxicity criteria. DISCUSSION: ILP still offer a high efficacy in selected patients. The main limitation of our review is the heterogeneity and age of most of the articles, as well as the absence of clinical trials comparing ILP with other procedures, making it difficult to transfer its results to the current era. CONCLUSIONS: ILP is still an effective and safe procedure for selected patients with unresectable melanoma of the limbs. In the era of targeted therapies and immunotherapy, ILP remains an acceptable and reasonable palliative treatment alternative, especially to avoid limb amputations. The ongoing clinical trials combining systemic therapies and ILP will provide more valuable information in the future to clarify the potential synergism of both strategies.

Chest computed tomography findings associated with severity and mortality in patients with COVID-19. / Hallazgos tomográficos pulmonares asociados a severidad y mortalidad en pacientes con la COVID-19.

OBJECTIVES: To determine chest CT findings associated with severity and mortality in patients with COVID-19 from the Hospital Nacional Edgardo Rebagliati Martins (HNERM) and propose cut-off values for a tomographic severity score (TSS). MATERIALS AND METHODS: A retrospective cohort study was conducted in 254 patients with COVID-19 who underwent chest CT as part of their initial evaluation at the emergency room; they were classified according to clinical severity. Main tomographic findings were described. A multivariate analysis with logistic regression was carried out to determine association with clinical severity, the Cox model was used to evaluate mortality, and ROC curves were elaborated to assess cutoff values for the TSS. RESULTS: CT findings associated with clinical severity were the following: diffuse pattern (OR: 3.23, 95% CI: 1.46-7.14), crazy-paving pattern (OR: 2.48; 95% CI: 1.08-5.68), and high TSS value (OR: 1.73; 95% CI: 1.49-2.02). The crazy-paving pattern (HR: 1.78; 95% CI: 1.03-3.06) and a high TSS value (HR: 1.33; 95% CI: 1.20-1.48) were found to be associated with mortality. A value of 7 in the TSS showed a sensibility of 94.4% and a specificity of 100% for moderate disease, and a value of 13 showed a sensibility of 84.9% and a specificity of 70.6% for severe disease. CONCLUSIONS: The diffuse pattern is associated with higher clinical severity. The crazy-paving pattern and a high TSS value are associated with higher clinical severity and mortality. We propose TSS cutoff values of 7 and 13 for moderate and severe disease, respectively.

OBJETIVOS: Determinar los hallazgos tomográficos pulmonares asociados a severidad y mortalidad en pacientes con la COVID-19 del Hospital Nacional Edgardo Rebagliati Martins (HNERM), y proponer puntos de corte para una puntuación tomográfica de severidad (PTS). MATERIALES Y MÉTODOS: Estudio de cohorte retrospectivo en 254 pacientes con la COVID-19 que contaban con tomografía de tórax clasificada según severidad clínica. Se realizó un análisis multivariado mediante regresión logística para determinar asociación con la severidad clínica, un análisis de regresión de Cox para evaluar mortalidad, y curvas ROC para evaluar la PTS. RESULTADOS: Los hallazgos tomográficos asociados a severidad clínica fueron el patrón difuso de las lesiones (OR: 3,23, IC 95%: 1,46-7,14), patrón en «empedrado¼ (OR: 2,48; IC 95%: 1,08-5,68) y mayor valor en la PTS (OR: 1,73; IC 95%: 1,49-2,02). Los hallazgos asociados a mortalidad fueron el patrón en «empedrado¼ (HR: 1,78; IC 95%: 1,03-3,06) y mayor valor en la PTS (HR: 1,33; IC 95%: 1,20-1,48). Un valor de 7 en la PTS tuvo una sensibilidad de 94,4% y especificidad de 100% para identificar casos moderados y un valor de 13 tuvo una sensibilidad de 84,9% y una especificidad de 70,6% para casos severos. CONCLUSIONES: El patrón difuso de las lesiones se asoció a una mayor severidad clínica. El patrón en «empedrado¼ y un mayor valor en la PTS se asociaron a mayor severidad clínica y a mortalidad. Se proponen los valores de 7 y 13 como puntos de corte de la PTS para identificar casos moderados y severos.

Bicyclic Diazepinones as Dual Ligands of the α2δ-1 Subunit of Voltage-Gated Calcium Channels and the Norepinephrine Transporter.

The synthesis and pharmacological activity of a new series of bicyclic diazepinones with dual activity toward the α2δ-1 subunit of voltage-gated calcium channels (Cavα2δ-1) and the norepinephrine transporter (NET) are reported. Exploration of the positions amenable for substitution on a nonaminoacidic Cavα2δ-1 scaffold allowed the identification of favorable positions for the attachment of NET pharmacophores. Among the patterns explored, attachment of the 2-ethylamino-9-methyl-6-phenyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-e][1,4]diazepin-5-one framework to the meta-position of the phenyl ring of the 3-methylamino-1-phenylpropoxy and 3-methylamino-1-thiophenylpropoxy moieties provided dual compounds with excellent NET functionality. Alternative bicyclic frameworks were also explored, and some lead molecules were identified, which showed a balanced dual profile and exhibited good ADMET properties.

Monitoring the Restoration of a Seventeenth-Century Wooden Artwork Using Laser-Induced Fluorescence and Digital Image Analysis.

The present paper is aimed at demonstrating the capabilities of digital image analysis (DIA) to support conservation of painted artwork. Laser-induced fluorescence (LIF) imaging has been usually used in the diagnosis of wall paintings. In this case, LIF is applied to the case study of a painted wooden canopy, and most successful data processing techniques are presented in the discussion of results. The Jesús del Gran Poder canopy, completed by Francisco Ruiz Gijón in 1692, is an oil panel painting on wood. Eight panels of the canopy have been study by LIF. This technique is capable of remotely acquiring hyperspectral images operating in fluorescence mode following ultraviolet laser excitation. LIF spectra combined with principal component analysis, spectral angle mapper, and DIA provide a chemical mapping of the treated wooden surface of the panels. Besides, LIF spectrum is as a fingerprint of the panels that allows stablishing differences between them. LIF imaging analysis has proven to be a very useful tool for mapping retouching work, tracking previous restorations, and detecting chemicals on the wood in order to monitor restorations.

Hallazgos tomográficos pulmonares asociados a severidad y mortalidad en pacientes con la COVID-19 / Chest Computed Tomography findings associated with severity and mortality in patients with COVID-19

Objetivos: Determinar los hallazgos tomográficos pulmonares asociados a severidad y mortalidad en pacientes con la COVID-19 del Hospital Nacional Edgardo Rebagliati Martins (HNERM), y proponer puntos de corte para una puntuación tomográfica de severidad (PTS). Materiales y métodos: Estudio de cohorte retrospectivo en 254 pacientes con la COVID-19 que contaban con tomografía de tórax clasificada según severidad clínica. Se realizó un análisis multivariado mediante regresión logística para determinar asociación con la severidad clínica, un análisis de regresión de Cox para evaluar mortalidad, y curvas ROC para evaluar la PTS. Resultados: Los hallazgos tomográficos asociados a severidad clínica fueron el patrón difuso de las lesiones (OR: 3,23, IC 95%: 1,46-7,14), patrón en «empedrado» (OR: 2,48; IC 95%: 1,08-5,68) y mayor valor en la PTS (OR: 1,73; IC 95%: 1,49-2,02). Los hallazgos asociados a mortalidad fueron el patrón en «empedrado» (HR: 1,78; IC 95%: 1,03-3,06) y mayor valor en la PTS (HR: 1,33; IC 95%: 1,20-1,48). Un valor de 7 en la PTS tuvo una sensibilidad de 94,4% y especificidad de 100% para identificar casos moderados y un valor de 13 tuvo una sensibilidad de 84,9% y una especificidad de 70,6% para casos severos. Conclusiones: El patrón difuso de las lesiones se asoció a una mayor severidad clínica. El patrón en «empedrado» y un mayor valor en la PTS se asociaron a mayor severidad clínica y a mortalidad. Se proponen los valores de 7 y 13 como puntos de corte de la PTS para identificar casos moderados y severos.

Objectives: To determine chest CT findings associated with severity and mortality in patients with COVID-19 from the Hospital Nacional Edgardo Rebagliati Martins (HNERM) and propose cut-off values for a tomographic severity score (TSS). Materials and Methods: A retrospective cohort study was conducted in 254 patients with COVID-19 who underwent chest CT as part of their initial evaluation at the emergency room; they were classified according to clinical severity. Main tomographic findings were described. A multivariate analysis with logistic regression was carried out to determine association with clinical severity, the Cox model was used to evaluate mortality, and ROC curves were elaborated to assess cutoff values for the TSS. Results: CT findings associated with clinical severity were the following: diffuse pattern (OR: 3.23, 95% CI: 1.46-7.14), crazy-paving pattern (OR: 2.48; 95% CI: 1.08-5.68), and high TSS value (OR: 1.73; 95% CI: 1.49-2.02). The crazy-paving pattern (HR: 1.78; 95% CI: 1.03-3.06) and a high TSS value (HR: 1.33; 95% CI: 1.20-1.48) were found to be associated with mortality. A value of 7 in the TSS showed a sensibility of 94.4% and a specificity of 100% for moderate disease, and a value of 13 showed a sensibility of 84.9% and a specificity of 70.6% for severe disease. Conclusions: The diffuse pattern is associated with higher clinical severity. The crazy-paving pattern and a high TSS value are associated with higher clinical severity and mortality. We propose TSS cutoff values of 7 and 13 for moderate and severe disease, respectively.

Thyroid Metastasis From Cutaneous Melanoma on an 18F-FDG PET/CT Study.

The thyroid gland is an uncommon location for metastasis. We report a 59-year-old woman with a history of cutaneous malignant melanoma. A unique hypermetabolic mass on the left thyroid lobe was identified by control F-FDG PET/CT scan, leading to dysphagia and stridor clinic. Total thyroidectomy and lymphadenectomy were performed with histopathological results concordant with metastasis from melanoma. Despite its rarity, finding focal thyroid lesions in patients with an oncological history should alert us, recommending that its metastatic etiology be ruled out.

Pneumonitis Related to Melanoma Immunotherapy.

Several regimens of immunotherapy have recently proven successful for multiple cancers, due to increased survival and quality of life. Rarely, immunotherapy with anti-programmed cell death protein 1 and programmed death-ligand 1 antibodies across cancer may cause immune-related pulmonary toxicity, with a low overall incidence, being particularly low among patients with melanoma and highest among individuals with lung cancer. In this vein, pulmonary toxicity is staged at 4 degrees according to the severity of the clinic and radiological findings, and its management is based on suppression of immunotherapy and administration of glucocorticoids. We report a case of pulmonary toxicity related to melanoma immunotherapy observed by F-FDG PET/CT.

Xantomas, la pieza clave para el diagnóstico de una hipertrigliceridemia grave / Xanthomas, the key piece for the diagnosis of a severe hypertriglyceridemia

Resumen La hipertrigliceridemia grave es una entidad poco común que presenta complicaciones que varían desde xantomas eruptivos y lipemia retinalis hasta pancreatitis, la cual puede llegar a ser mortal. No hay valores absolutos de niveles de triglicéridos con los que los pacientes desarrollen complicaciones, por lo que es difícil determinar la necesidad de manejo intrahospitalario en pacientes asintomáticos. Presentamos el caso de un paciente de 47 años con hipertrigliceridemia grave, quien como único signo clínico presentaba xantomas generalizados. Se realiza una discusión del tema y revisión de la literatura.

Abstract Severe hypertriglyceridemia is a rare entity that presents complications ranging from eruptive xanthomas and lipemia retinalis to pancreatitis, which can be fatal. There are no absolute values of triglyceride levels with which patients develop complications, so it is difficult to determine the need for in-hospital management in asymptomatic patients. We present the case of a 47-year-old patient with severe hypertriglyceridemia, who presented generalized xanthomas as the only clinical sign. A discussion of the topic and review of the literature is made.

Discovery of potent calpain inhibitors based on the azolo-imidazolidenone scaffold.

A series of new azolopyrimidine-peptide hybrids and indolomethylideneimidazolones were obtained and evaluated as calpain inhibitors. The hybrid compounds were inactive, whereas some members of the initial azolomethylideneimidazolone series showed interesting calpain inhibitory activity. By using 4b as a hit compound, a new series of analogs were synthesized by an efficient synthetic procedure based on a multicomponent reaction followed by an unprecedented reaction at the methylene position of the molecule. The best inhibitor found for calpain I (IC50 = 20 nM) was about 20 times more potent than the hit compound. Studies on 4b showed that its inhibition is consistent with an uncompetitive inhibition mode. This compound did not exhibit cellular toxicity at any of the doses tested (0.1-10 µM) and further studies indicated that it was capable of blockading chemical ischemia induction of apoptosis by preventing sodium azide-dependent calpain activation in intact human kidney tubular epithelial cells. The results of molecular modeling studies rationalized the inhibitory activity found for this series and account, from a structural point of view, for the most active compound identified (4j).

Virchow Node From Prostate Carcinoma by 18F-Choline PET/CT.

F-choline PET/CT is increasingly being used during the follow-up of prostate cancer and is bringing us valuable information for the delineation of local and distant nodal recurrence in patients with hormone-resistant poorly differentiated cell types. Lymphatic spreading usually involves pelvic and retroperitoneal levels, being unusual at supraclavicular levels. We report a 75-year-old man with unsuspected involvement of Virchow node from prostate cancer observed using F-choline PET/CT.