Predictive modeling of endocardial fibroelastosis recurrence in patients with congenital heart disease.

BACKGROUND: Endocardial fibroelastosis (EFE) is a major effector in the maldevelopment of the heart in patients with congenital heart disease. Despite successful surgical removal, EFE can redevelop, but the underlying cause of EFE recurrence remains unknown. This study aimed to identify hemodynamic predictors and genetic links to epithelial/endothelial-to-mesenchymal transition (EMT/EndMT) alterations for preoperative risk assessment. METHODS: We assessed the impact of preoperative hemodynamic parameters on EFE recurrence in a cohort of 92 patients with congenital heart disease who underwent left ventricular (LV) EFE resection between January 2010 and March 2021. Additionally, whole-exome sequencing in 18 patients was used to identify rare variants (minor allele frequency <10-5) in high-expression heart (HHE) genes related to cardiac EMT/EndMT and congenital heart disease. RESULTS: EFE recurred in 55.4% of patients, within a median of 2.2 years postsurgery. Multivariable analysis revealed specific hemodynamic parameters (mitral valve inflow and area, LV filling pressure, and aortic valve gradient and diameter) as predictors, forming a predictive model with an area under the receiver operating characteristic curve of 0.782. Furthermore, 89% of the patients exhibited damaging variants in HHE genes, with 38% linked to cardiac EMT/EndMT Gene Ontology processes and 22% associated with known congenital heart disease genes. Notably, HHE genes associated with cardiac EMT/EndMT were significantly associated with faster EFE recurrence in a multivariate analysis (hazard ratio, 3.56; 95% confidence interval, 1.24-10.17; P = .018). CONCLUSIONS: These findings established a predictive scoring system using preoperative hemodynamic parameters for EFE recurrence risk assessment. Alterations in HHE genes, particularly those linked to cardiac EMT/EndMT, exacerbate the risk of recurrence.

TPX2 overexpression promotes sensitivity to dasatinib in breast cancer by activating YAP transcriptional signaling.

Chromosomal instability (CIN) is a hallmark of cancer aggressiveness, providing genetic plasticity and tumor heterogeneity that allows the tumor to evolve and adapt to stress conditions. CIN is considered a cancer therapeutic biomarker because healthy cells do not exhibit CIN. Despite recent efforts to identify therapeutic strategies related to CIN, the results obtained have been very limited. CIN is characterized by a genetic signature where a collection of genes, mostly mitotic regulators, are overexpressed in CIN-positive tumors, providing aggressiveness and poor prognosis. We attempted to identify new therapeutic strategies related to CIN genes by performing a drug screen, using cells that individually express CIN-associated genes in an inducible manner. We find that the overexpression of targeting protein for Xklp2 (TPX2) enhances sensitivity to the proto-oncogene c-Src (SRC) inhibitor dasatinib due to activation of the Yes-associated protein 1 (YAP) pathway. Furthermore, using breast cancer data from The Cancer Genome Atlas (TCGA) and a cohort of cancer-derived patient samples, we find that both TPX2 overexpression and YAP activation are present in a significant percentage of cancer tumor samples and are associated with poor prognosis; therefore, they are putative biomarkers for selection for dasatinib therapy.

Nuclear VANGL2 Inhibits Lactogenic Differentiation.

Planar cell polarity (PCP) proteins coordinate tissue morphogenesis by governing cell patterning and polarity. Asymmetrically localized on the plasma membrane of cells, transmembrane PCP proteins are trafficked by endocytosis, suggesting they may have intracellular functions that are dependent or independent of their extracellular role, but whether these functions extend to transcriptional control remains unknown. Here, we show the nuclear localization of transmembrane, PCP protein, VANGL2, in the HCC1569 breast cancer cell line, and in undifferentiated, but not differentiated, HC11 cells that serve as a model for mammary lactogenic differentiation. The loss of Vangl2 function results in upregulation of pathways related to STAT5 signaling. We identify DNA binding sites and a nuclear localization signal in VANGL2, and use CUT&RUN to demonstrate recruitment of VANGL2 to specific DNA binding motifs, including one in the Stat5a promoter. Knockdown (KD) of Vangl2 in HC11 cells and primary mammary organoids results in upregulation of Stat5a, Ccnd1 and Csn2, larger acini and organoids, and precocious differentiation; phenotypes are rescued by overexpression of Vangl2, but not Vangl2ΔNLS. Together, these results advance a paradigm whereby PCP proteins coordinate tissue morphogenesis by keeping transcriptional programs governing differentiation in check.

Immunomodulation with AM3 and antioxidants creates an adequate framework for skin repair and decreases the monocyte proinflammatory stage in smoker women.

Smoking has been considering a crucial factor in promoting skin and systemic aging that is associated with the development of a low-level, systemic, chronic inflammation known as "inflammaging" in which monocytes play a pivotal role. Our aim was to investigate the effects of AM3 plus antioxidants vs placebo in the activation status, function of monocytes and cutaneous aging parameters in healthy smoker middle-aged women. A total of 32 women were 1:1 randomly assigned to AM3 plus antioxidants or placebo for three months. Peripheral mononuclear blood cells and cutaneous biopsy were obtained and flow cytometry and immunohistological studies, respectively, were performed before and after the treatment. AM3 plus antioxidants treatment compared with placebo significantly reduced the monocyte production of the proinflammatory interleukin 1 (IL-1), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) cytokines as well as increased the regulatory IL-10 in middle-aged smoker women. Furthermore, AM3 and antioxidants did not modify ROS production by monocytes and granulocytes but increased their phagocytic activity. The active combination also stimulated a significative increase in reticular dermis depth as well as an increase in the expression of CD117 and CD31. Thus, AM3 and antioxidants treatment reduces the systemic proinflammatory monocyte disturbance of heathy smoker middle-aged women and encourage skin repair mechanisms.

Regular Exercise Improved Fatigue and Musculoskeletal Pain in Young Adult Psoriatic Patients without Psoriatic Arthritis.

Fatigue and musculoskeletal pain are also frequent in patients with psoriasis (PsO) without arthritis (PsA). The current study aimed to assess the impact of an intervention program based on aerobic training to reduce fatigue and musculoskeletal pain in patients with PsO without PsA. A total of 118 male patients with PsO volunteered in the current interventional study and were randomly allocated to the experimental (n = 59) or control group (n = 59). The intervention consisted of a 16-week aerobic training program on a treadmill, three sessions per week, consisting of a warm-up, 35-50 min treadmill exercise (increasing 5 min/4 weeks) at a work intensity of 50-65% of peak heart-rate (increasing 5%/4 weeks), and cooling-down. The functional assessment of chronic illness therapy fatigue scale (FACIT-Fatigue), health assessment questionnaire disability index (HAQ-DI), and visual analog scale (VAS) were compared pre and post intervention. Nutritional intake, maximal aerobic power, lipid profile, serum markers of muscle damage, and body composition were also assessed. When compared to baseline, FACIT-Fatigue, HAQ-DI, and VAS scores were significantly improved without increasing markers of muscle damage. Fat mass percentage, lipid profile, and maximal oxygen consumption were also improved. In conclusion, a 16-week aerobic training program at moderate intensity was safe, well tolerated, and effective in psoriatic patients without PsA. Long-term follow-up studies are required to examine whether these promising results may improve clinical outcomes.

Usefulness of Preoperative Determination of Serum MR-ProAdrenomedullin Levels to Predict the Need for Postoperative Organ Support in Abdominal Oncological Surgery.

The need for postoperative organic support is associated with patient outcomes. Biomarkers may be useful for detecting patients at risk. MR-ProADM is a novel biomarker with an interesting profile that can be used in this context. The main objective of this study was to verify whether there was an association between the preoperative serum levels of MR-ProADM and the need for organic support after elective abdominal cancer surgery, and to determine the preoperative MR-ProADM value that predicts the need for postoperative organic support. This was a multicenter prospective observational study conducted by four tertiary hospitals in Spain between 2017 and 2018. Plasma samples were collected for the quantification of MR-ProADM from adults who underwent major abdominal surgery during 2017-2018. The primary outcome was the need for organic support in the first seven postoperative days and its association with the preoperative levels of MR-ProADM, and the secondary outcome was the preoperative levels of MR-ProADM in the study population. This study included 370 patients with a mean age of 67.4 ± 12.9 years. Seventeen percent (63 patients) required some postoperative organic support measures in the first week. The mean preoperative value of MR-ProADM in patients who required organic support was 1.16 ± 1.15 nmol/L. The AUC-ROC of the preoperative MR-ProADM values associated with the need for organic support was 0.67 (95% CI: 0.59-0.75). The preoperative MR-ProADM value, which showed the best compromise in sensitivity and specificity for predicting the need for organic support, was 0.70 nmol/L. The negative predictive value was 91%. A multivariate analysis confirmed that a preoperative level of MR-ProADM ≥ 0.70 nmol/L is an independent factor associated with risk of postoperative organic support (OR 2, 6). Elevated preoperative MR-ProADM levels are associated with the need for postoperative organic support. Therefore, MR-ProADM may be a useful biomarker for perioperative risk assessment.

Whole-Genome Doubling as a source of cancer: how, when, where, and why?

Chromosome instability is a well-known hallmark of cancer, leading to increased genetic plasticity of tumoral cells, which favors cancer aggressiveness, and poor prognosis. One of the main sources of chromosomal instability are events that lead to a Whole-Genome Duplication (WGD) and the subsequently generated cell polyploidy. In recent years, several studies showed that WGD occurs at the early stages of cell transformation, which allows cells to later become aneuploid, thus leading to cancer progression. On the other hand, other studies convey that polyploidy plays a tumor suppressor role, by inducing cell cycle arrest, cell senescence, apoptosis, and even prompting cell differentiation, depending on the tissue cell type. There is still a gap in understanding how cells that underwent WGD can overcome the deleterious effect on cell fitness and evolve to become tumoral. Some laboratories in the chromosomal instability field recently explored this paradox, finding biomarkers that modulate polyploid cells to become oncogenic. This review brings a historical view of how WGD and polyploidy impact cell fitness and cancer progression, and bring together the last studies that describe the genes helping cells to adapt to polyploidy.

Knowledge and practices about taeniasis/cysticercosis complex within the framework of the national plan for its elimination in Colombia, 2019.

The taeniasis/cysticercosis complex (TCC) belongs to the group of neglected infectious diseases with a multifactorial transmission that includes hosts such as humans and pigs of the parasitic tapeworm (Taenia solium) and environmental factors. This study represents the first phase of the National and Cross-sectoral Plan for TCC Elimination. OBJECTIVES: To obtain data about knowledge and practices in relation to the TCC from knowledge, attitudes, and practices (KAP) surveys applied in two pilot localities for building a baseline of the potential risk factors related to identification, prevention, and control of TCC in Colombia. METHODS: A descriptive cross-sectional survey from October to November in 2019 was carried out using a structured questionnaire and random sampling by single-stage conglomerates in the municipalities of Mahates, Bolívar (n = 152) (Atlantic Region) and Mercaderes, Cauca (n = 152) (Andean Region). RESULTS: Respondents in Mahates showed moderate knowledge about TCC compared to those in Mercaderes, however, risky practices were identified in both places (consumption of pork with cysts and defecation in places other than the bathroom or latrine). Deficiency in infrastructure and failure in basic services were observed as potential risk factors for TCC transmission in both municipalities. CONCLUSION: Based on the framework of the National and Cross-sectoral Plan for TCC Elimination, adequate knowledge on identification, prevention, and control of the disease must be reinforced; cultural and ecological differences should be considered when designing communication and knowledge transmission tools. We consider that major investment should be made in improving basic services and creating sustainable modernized pig farming in Mahates and Mercaderes.

Ceefourin-1, a MRP4/ABCC4 inhibitor, induces apoptosis in AML cells enhanced by histamine.

BACKGROUND: Ceefourin-1 is a specific MRP4/ABCC4 inhibitor with potential antileukemic activity. In this study, we evaluate the ability of ceefourin-1 alone or in combination with histamine, an approved antileukemic agent, to induce cell differentiation or apoptosis in human acute myeloid leukemic cells. We also examine ceefourin-1 toxicity in mice. METHODS: U937, HL-60, and KG1a cells were used as models for human acute myeloid leukemia. Cyclic AMP efflux was estimated by measuring intracellular and extracellular cAMP levels. Cell differentiation was assessed by levels of CD14 and CD11b by FACS, and CD88 by western blot, and by cell morphology. Apoptosis was evaluated by cleavage of caspase-3 and PARP by western blot, and by annexin V binding assay. Subacute toxicity study of ceefourin-1 was carried out in BALB/c mice. RESULTS: Ceefourin-1 inhibits cAMP exclusion in AML cells and promotes intracellular signaling via CREB. Ceefourin-1 leads AML cells to apoptosis and histamine potentiates this effect, without evidence of cell differentiation. Intraperitoneal administration of ceefourin-1 shows no important alterations in mice blood parameters, hepatic, and renal functions, nor signs of histologic damage. CONCLUSIONS: These results show that ceefourin-1 promotes apoptosis in AML cells that is enhanced by histamine. GENERAL SIGNIFICANCE: This work indicates that ceefourin-1 represents a promising molecule that could be used alone or in combination with histamine for in vivo evaluation in acute myeloid leukemia malignancies.

DNA damage triggers squamous metaplasia in human lung and mammary cells via mitotic checkpoints.

Epithelial transdifferentiation is frequent in tissue hyperplasia and contributes to disease in various degrees. Squamous metaplasia (SQM) precedes epidermoid lung cancer, an aggressive and frequent malignancy, but it is rare in the epithelium of the mammary gland. The mechanisms leading to SQM in the lung have been very poorly investigated. We have studied this issue on human freshly isolated cells and organoids. Here we show that human lung or mammary cells strikingly undergo SQM with polyploidisation when they are exposed to genotoxic or mitotic drugs, such as Doxorubicin or the cigarette carcinogen DMBA, Nocodazole, Taxol or inhibitors of Aurora-B kinase or Polo-like kinase. To note, the epidermoid response was attenuated when DNA repair was enhanced by Enoxacin or when mitotic checkpoints where abrogated by inhibition of Chk1 and Chk2. The results show that DNA damage has the potential to drive SQM via mitotic checkpoints, thus providing novel molecular candidate targets to tackle lung SCC. Our findings might also explain why SCC is frequent in the lung, but not in the mammary gland and why chemotherapy often causes complicating skin toxicity.

Assessment of clinical and ultrasonographic parameters as indicators for buccal fat pad excision by esthetic reasons.

PURPOSE: The selection of candidates for buccal fat pad (BFP) removal depends on the patient's requirements, the subjective surgeons' evaluation, and objective clinical factors. This cross-sectional observational study aimed to identify objective clinical and ultrasonographic parameters as indicators of cheek contouring with BFP excision. METHODS: Sixty-six patients with cheek fullness complaints were examined by two experienced surgeons to determine if they were good candidates for the procedure. Thereafter, participants underwent clinical and ultrasonographic assessments in a separate session to aid in the surgical decision-making. The association between the clinical judgment for BFP excision and the study variables was analyzed individually and adjusted for confounders using binary logistic regression and grouping analyses. RESULTS: Forty-nine participants were regarded as suitable and 17 as non-suitable for the procedure. After regression analysis, cheek skin-fold thickness > 6.00 mm, midfacial contour > 2.20 mm, ovoid/triangular facial form, and ultrasonographic BFP volume > 2.05 mL remained as robust individual indicators for the suitability for the procedure. However, the grouping analysis showed that patients having three-to-four significant criteria synchronously had significantly higher odds for eligibility with excellent discrimination capability. CONCLUSION: Although high values of cheek skin-fold thickness, midfacial contour, and ultrasonographic BFP volume, as well as an ovoid/triangular facial form, might be robust indicators for the suitability for BFP excision, the surgical decision-making should not be based on isolated parameters. Instead, those patients possessing a combination of at least three of these specific eligibility criteria above the threshold value might be considered the best candidates for the procedure.

Caracterización y factores asociados con la atención de embarazadas con dengue en Cali, Colombia / Characterization and factors associated with the care of pregnant women with dengue in Cali, Colombia

Resumen OBJETIVO: Describir las características sociodemográficas y clínicas y determinar los factores asociados con la hospitalización y la oportunidad de consulta en embarazadas notificadas con dengue en Cali, Colombia. MATERIALES Y MÉTODOS: Estudio observacional, analítico y retrospectivo de base poblacional. Descripción de las características sociodemográficas y clínicas de las embarazadas con dengue que se notificaron al Sistema de Vigilancia en Salud Pública (SIVIGILA). Para identificar los factores asociados con la hospitalización se aplicó un modelo de regresión logística y para el procesamiento estadístico se utilizó SPSS versión 26. RESULTADOS: Se estudiaron 674 embarazadas con dengue, 63.9% (n = 431) sin signos de alarma, 36.1% (n = 243) con signos de alarma y ningún caso de dengue grave. En cuanto a la conducta, el 42.3% ( n = 285) se trató de manera ambulatoria, 39.5% (n = 266) en el hospital;12.5% (n = 84) permaneció en observación, 1.9% (n = 13) requirió el envío a otro centro de salud para su hospitalización y el 3.9% (n = 26) requirió atención en cuidados intensivos. CONCLUSIONES: En las embarazadas, la infección por dengue aumenta la morbilidad; los principales factores asociados con la hospitalización fueron: trombocitopenia, hipotensión, dolor abdominal, erupción cutánea y vómito. Por parte de las entidades de salud y la comunidad se requieren intervenciones efectivas enfocadas a la manipulación de residuos y educación e insistencia en los principales signos de alarma por los que deben solicitar la consulta médica.

Abstract OBJECTIVE: To describe the sociodemographic and clinical characteristics and to determine the factors associated with hospitalization and timeliness of consultation in pregnant women notified with dengue fever in Cali, Colombia. MATERIALS AND METHODS: Observational, analytical and retrospective population-based study. Description of the sociodemographic and clinical characteristics of pregnant women with dengue reported to the Public Health Surveillance System (SIVIGILA). A logistic regression model was applied to identify factors associated with hospitalization and SPSS version 26 was used for statistical processing. RESULTS: A total of 674 pregnant women with dengue were studied, 63.9% (n = 431) without alarm signs, 36.1% (n = 243) with alarm signs and no cases of severe dengue. In terms of behavior, 42.3% ( n = 285) were treated on an outpatient basis, 39.5% (n = 266) in hospital;12.5% (n = 84) remained under observation, 1.9% (n = 13) required referral to another health center for hospitalization and 3.9% (n = 26) required intensive care. CONCLUSIONS: In pregnant women, dengue infection increases morbidity; the main factors associated with hospitalization were: thrombocytopenia, hypotension, abdominal pain, rash, and vomiting. On the part of the health entities and the community, effective interventions focused on waste handling and education and insistence on the main warning signs for which they should seek medical consultation are required.

Correlación entre dos metodologías para la medición de anticuerpos contra la proteína spike del coronavirus del Síndrome Respiratorio Agudo Grave 2 / Correlation between two methodologies for the measurement of antibodies against the spike protein of coronavirus of the Severe Acute Respiratory Syndrome 2

Resumen El coronavirus del Síndrome Respiratorio Agudo Grave 2 (SARS-CoV-2) posee diversas proteínas estructurales que incluyen la proteína spike (S), principal blanco de las vacunas actuales. Existen diversas metodologías para la medición de anticuerpos contra ésta que brindan información acerca de la respuesta inmune frente a la vacunación. El objetivo de este trabajo fue determinar la correlación entre quimioluminiscencia (CLIA) y enzimoinmunoanálisis de adsorción (ELISA) para la medición de anticuerpos IgG anti-proteína S (IgG anti-S). Se recolectaron resultados serológicos de 169 individuos y se determinaron los niveles de anticuerpos por ambas metodologías. Del total de muestras, 106 arrojaron un resultado positivo por ambas metodologías y 15 resultaron discordantes (CLIA+, ELISA-), con índice Kappa de 0,80. La correlación entre ambas metodologías fue buena. Este estudio podría aportar al manejo y seguimiento de la población vacunada, con la finalidad de obtener un valor de corte para evaluar la aplicación de una dosis adicional.

Abstract Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) has several structural proteins including the spike (S) protein, which is the main target of current vaccines. There are various methodologies for the measurement of antibodies against it that provide information about the immune response to vaccination. The objective of this study was to determine the correlation between chemiluminescence (CLIA) and enzyme-linked immunoassay (ELISA) for the measurement of IgG anti-S protein (IgG anti-S) antibodies. Serological results were collected from 169 individuals and antibody levels were determined by both methodologies. Out of the total samples, 106 were positive by both methodologies and 15 were discordant (CLIA+, ELISA-), with a Kappa index of 0.80. The correlation between both methodologies was good. This study could contribute to the management and follow-up of the vaccinated population, in order to obtain a cut-off value to evaluate the application of an additional dose.

Resumo O coronavírus da Síndrome Respiratória Aguda Grave 2 (SARS-CoV-2) possui várias proteínas estruturais, incluindo a proteína spike (S), principal alvo das vacinas atuais. Existem várias metodologias para medir anticorpos contra ela que fornecem informações sobre a resposta imune diante da vacinação. O objetivo deste trabalho foi determinar a correlação entre quimioluminescência (CLIA) e enzimoimunoanálise de absorção (ELISA) para a medição de anticorpos IgG anti-proteína S (IgG anti-S). Foram coletados resultados sorológicos de 169 indivíduos e os níveis de anticorpos foram determinados por ambas as metodologias. Do total de amostras, 106 deram resultados positivos nas duas metodologias e 15 foram discordantes (CLIA+, ELISA-), com índice Kappa de 0,80. A correlação entre as duas metodologias foi boa. Este estudo poderia contribuir para a gestão e seguimento da população vacinada, visando a obter um valor de corte para avaliar a aplicação de uma dose adicional.

The Integration of Cell Therapy and Biomaterials as Treatment Strategies for Remyelination.

Multiple sclerosis (MS) is a chronic degenerative autoimmune disease of the central nervous system that causes inflammation, demyelinating lesions, and axonal damage and is associated with a high rate of early-onset disability. Disease-modifying therapies are used to mitigate the inflammatory process in MS but do not promote regeneration or remyelination; cell therapy may play an important role in these processes, modulating inflammation and promoting the repopulation of oligodendrocytes, which are responsible for myelin repair. The development of genetic engineering has led to the emergence of stable, biocompatible biomaterials that may promote a favorable environment for exogenous cells. This review summarizes the available evidence about the effects of transplantation of different types of stem cells reported in studies with several animal models of MS and clinical trials in human patients. We also address the advantages of combining cell therapy with biomaterials.

Hipercolesterolemia familiar descripción de un caso en una familia de Armenia - Quindío (Colombia)

Introducción: La Hipercolesterolemia familiar (HF) es una enfermedad genética de carácter autosómico dominante, poco frecuente, generada por la mutación en el cromosoma 19. Es la primera causa de enfermedad cardiovascular prematura. Las mutaciones patogénicas que generan la HF se relacionan con el receptor de LDL (LDLr), la apolipoproteina B-100 (Apo- B100) y la proteína convertasa subtilisina / kexina tipo 9 (PCSK9), que produce elevación del colesterol y alteración de la vía del LDLr en el 80 % de los casos diagnosticados de HF (5). Presentamos un reporte de caso de cuatro pacientes que pertenecen a la misma familia, quienes presentan mutaciones patogénicas de diferente compromiso a nivel cardiovascular y sistémico que ha afectado de manera negativa su cotidianidad. El objetivo de este trabajo es realizar una correlación del hipercolesterolemia familiar de tipo genético a partir de la literatura, con respecto a la serie de casos presentada, y evaluar el impacto que este genera en los servicios de salud, en la vida del paciente y su familia. Discusión: El reporte de caso que presentamos se fundamenta en la sospecha de HF según los criterios de Holanda. En estos pacientes se reconoce mutación del gen LDLr que se relaciona con HF. Sin embargo, no ha sido ampliamente estudiada. Chmara realizó en Polonia por primera vez un estudio en el que reportó la variante ac 11G>T. En Colombia, el estudio de López encontró tres mutaciones, identificadas como variante a c.11G > A, n c.416A > G y c.1187G > A (8). Conclusión: La HF en nuestro medio es poco frecuente y con gran impacto social, en la mayoría de los casos genera síntomas clínicos y aumento del riesgo cardiovascular desde una edad temprana. Es importante resaltar el diagnóstico oportuno y el conocimiento por parte del personal de salud para generar una calidad de vida adecuada a los pacientes y evitar que aumente el riesgo cardiovascular.

Introduction: Familial hypercholesterolemia (FH) is a rare autosomal dominant genetic disease caused by a chromosome 19 mutation. It is the main cause of premature cardiovascular disease. Pathogenic mutations which cause FH are related to the LDL receptor (LDLr), B-100 apolipoprotein (Apo-B100) and type 9 subtilisin/kexin convertase protein (PCSK9), causing blood cholesterol increase and impairment of the LDLr pathway in up to 80% of patients diagnosed with FH. We present the case of 4 patients belonging to the same family and who present pathogenic mutations leading to diverse kinds of cardiovascular and systemic disease. Discussion: The case report we are presenting is based on the suspicion of FH according to the dutch criteria. These patients had the LDLr gene mutation related to FH. However, this mutation has not been thoroughly studied. The ac 11G>T variant was reported for the first time in Poland by Chmara. In Colombia, Lopez found 3 mutations identified as variant a c.11G > A, variant n c.416A > G and variant c.1187G > A. Conclusion: FH is rare in Colombia. Early diagnosis and healthcare worker awareness must be highlighted to improve the quality of life and decrease the cardiovascular risk of patients.

Recommendations regarding emergency head and neck procedures during coronavirus disease-2019.

The coronavirus disease-2019 (COVID-19) has spread globally and is considered a world health emergency. Healthcare professionals represent an important percentage of the infected population, with otolaryngologists and head and neck surgeons at particular risk. Elective procedures have been strongly discouraged, but urgent disorders still entail a hazardous setting. We performed a non-systematic review of the publications and guidelines regarding Head and Neck surgical emergencies management in the context of the COVID-19 pandemic. The literature describing management of the disease was also reviewed to adapt conventional treatment to the present circumstances. A concise and specific compilation of practical recommendations was made with the aim of improving management of emergencies involving the head and neck region, while offering a safe alternative for patients and healthcare providers. In addition, we have made a brief summary of how these recommendations were adapted based on our socio-economic background and available health resources.

La enfermedad del coronavirus-2019 (COVID-19) se ha extendido a nivel mundial y se considera una emergencia sanitaria mundial. Los profesionales sanitarios representan un porcentaje importante de la población infectada, y los otorrinolaringólogos y cirujanos de cabeza y cuello corren un riesgo especial. Se han desaconsejado enérgicamente los procedimientos electivos, pero los trastornos urgentes aún implican un entorno peligroso. Realizamos una revisión no sistemática de las publicaciones y guías sobre el manejo de emergencias quirúrgicas de cabeza y cuello en el contexto de la pandemia de COVID-19. También se revisó la literatura que describe el manejo de la enfermedad con el fin de adaptar el tratamiento convencional a las circunstancias actuales. Se realizó una recopilación concisa y específica de recomendaciones prácticas con el objetivo de mejorar el manejo de las emergencias que involucran la región de la cabeza y el cuello, al tiempo que ofrece una alternativa segura para los pacientes y los proveedores de atención médica. Además, hemos hecho un breve resumen de cómo se adaptaron estas recomendaciones en función de nuestros antecedentes socioeconómicos y los recursos de salud disponibles.

Total Temporomandibular Joint Replacement and Simultaneous Orthognathic Surgery Using Computer-Assisted Surgery.

BACKGROUND: Disorders of the temporomandibular joint (TMJ) are frequent and are usually associated with other disorders of the facial skeleton. Surgery might be needed to correct TMJ anatomy and function and, in cases where pathologies coexist, a two-stage corrective surgery might be needed. However, the current fashion of single-stage procedures is feasible with the aid of new technologies such as computer-assisted surgery (CAS). This is a step forward toward performing complex procedures such as a TMJ replacement with simultaneous orthognathic surgery. CAS allows designing patient-fitted prosthesis and more predictable and accurate surgeries. Moreover, intraoperative development can be controlled in real time with intraoperative navigation, and postoperative results can be measured and compared afterwards. AIMS: The primary purpose of this article is to present the protocol used in our institution for orthognathic surgery associated with unilateral and bilateral TMJ replacement with patient-fitted prostheses guided with CAS. MATERIALS AND METHODS: We present two cases to illustrate our protocol and its results. RESULTS: In the first case, the difference in millimeters between planning and surgical outcomes was 1.72 mm for the glenoid component and 2.16 mm for the condylar prosthesis; for the second case, differences in the right side were 2.59 mm for the glenoid component and 2.06 mm for the ramus, and in the left side, due to the anatomy the difference was a little greater, without clinical significance. CONCLUSION: Combined surgery of the midface and mandible with total TMJ replacement is feasible and beneficial for the patient. CAS facilitates the planning and design of custom-fit prosthesis and execution of these procedures.

Impact of Biological Agents on Imaging and Biomarkers of Cardiovascular Disease in Patients with Psoriasis: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.

BACKGROUND: The effect of biologics on the risk for cardiovascular disease in patients with psoriasis is still unclear despite their widespread use. OBJECTIVE: The objective of this study was to examine the impact of licensed biological therapies on imaging and biomarkers of cardiovascular disease risk in patients with psoriasis by a systematic review and meta-analysis of placebo-controlled trials. METHODS: A comprehensive search of studies published before 1 June 2020 was performed in Medline-Ovid, EMBASE, and CENTRAL using a predefined strategy to identify relevant articles. RESULTS: Five studies were included for the final examination, and two studies were included in the meta-analysis. We did not find a significant reduction in aortic vascular inflammation in patients treated with adalimumab compared with those who received placebo at weeks 12-16. There was no beneficial effect on imaging biomarkers (aortic vascular inflammation or flow-mediated dilatation) of cardiovascular disease risk in patients exposed to biological therapies (adalimumab and secukinumab) compared with those exposed to placebo, except for ustekinumab showing a reduction in aortic vascular inflammation at week 12 but not at week 52 after the open-label extension period. The strongest reduction in blood-based cardiometabolic risk biomarkers was observed with adalimumab (CRP, TNF-α, IL-6, and GlycA) and phototherapy (CRP and IL-6) compared with that observed with placebo. CONCLUSIONS: Randomized controlled trials show that ustekinumab reduces aortic vascular inflammation and that TNF-α inhibitors and phototherapy reduce CRP and IL-6. These surrogate marker findings require randomized controlled trials evaluating cardiovascular events to inform clinical practice.

Actividad lúpica en paciente con enfermedad renal terminal: reporte de caso / Lupus activity in a patient with end-stage renal disease: a case report

RESUMEN El lupus eritematoso sistémico (LES) es una enfermedad autoinmune que afecta múltiples órganos; el compromiso renal se encuentra en el 50% de los pacientes y es variable de acuerdo con el grupo racial y étnico. Se estima que el 10% de los pacientes con nefritis lúpica (NL) desarrollan enfermedad renal terminal (ERT) y, una vez que se da la progresión, el 80% de los pacientes negativizan los marcadores de actividad. Sin embargo, aunque es inusual, la reactivación de la enfermedad puede presentarse en compromiso renal avanzado y es importante diagnosticarla oportunamente para definir la causa, tratarla y evitar complicaciones. Presentamos el caso clínico de una paciente de 45 arios, con ERT en diálisis peritoneal, que se encontraba en remisión de la enfermedad y posteriormente desarrolló actividad lúpica.

ABSTRACT Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple organs, and renal involvement is found in 50% of patients and is variable according to racial and ethnic group. It is estimated that 10% of patients with lupus nephritis (NL) develop end-stage renal disease (ERT), and once progression occurs, 80% of patients are negative for activity markers. However, although it is rare, the reactivation of the disease can occur in advanced renal involvement, and it is important to diagnose it in a timely manner to define the cause and treat it, avoiding complications.