Dynamic BTB-domain filaments promote clustering of ZBTB proteins.

The formation of dynamic protein filaments contributes to various biological functions by clustering individual molecules together and enhancing their binding to ligands. We report such a propensity for the BTB domains of certain proteins from the ZBTB family, a large eukaryotic transcription factor family implicated in differentiation and cancer. Working with Xenopus laevis and human proteins, we solved the crystal structures of filaments formed by dimers of the BTB domains of ZBTB8A and ZBTB18 and demonstrated concentration-dependent higher-order assemblies of these dimers in solution. In cells, the BTB-domain filamentation supports clustering of full-length human ZBTB8A and ZBTB18 into dynamic nuclear foci and contributes to the ZBTB18-mediated repression of a reporter gene. The BTB domains of up to 21 human ZBTB family members and two related proteins, NACC1 and NACC2, are predicted to behave in a similar manner. Our results suggest that filamentation is a more common feature of transcription factors than is currently appreciated.

Clinical Reasoning: A 60-Year-Old Woman With Rapidly Progressive Muscle Weakness and Ophthalmoparesis.

The clinical assessment of patients with proximal muscle weakness represents a frequent yet intricate challenge. We present the case of a 60-year-old woman who experienced a progressive, symmetrical weakness in proximal limbs and bulbar muscles over 6 months. Notable clinical findings included bilateral ophthalmoparesis; widespread muscle atrophy; and pronounced weakness in craniobulbar, cervical, and proximal muscles, more severe than in distal ones. We elucidate a methodical diagnostic approach, focusing on constructing a comprehensive differential diagnosis and identifying potential causes of proximal muscle weakness. Special emphasis is placed on exploring the etiologies in cases presenting with both progressive muscle weakness and ophthalmoparesis. We further describe the role of muscle biopsy results and their integration with genetic testing outcomes.

Gutless Helper-Dependent and First-Generation HAdV5 Vectors Have Similar Mechanical Properties and Common Transduction Mechanisms.

Delivering vectorized information into cells with the help of viruses has been of high interest to fundamental and applied science, and bears significant therapeutic promise. Human adenoviruses (HAdVs) have been at the forefront of gene delivery for many years, and the subject of intensive development resulting in several generations of agents, including replication-competent, -defective or retargeted vectors, and recently also helper-dependent (HD), so-called gutless vectors lacking any viral protein coding information. While it is possible to produce HD-AdVs in significant amounts, physical properties of these virus-like particles and their efficiency of transduction have not been addressed. Here, we used single-cell and single virus particle assays to probe the effect of genome length on HAdV-C5 vector transduction. Our results demonstrate that first-generation C5 vectors lacking the E1/E3 regions of the viral genome as well as HD-AdV-C5 particles with a wild type (wt) ∼36 kbp or an undersized double-strand DNA genome are similar to human adenovirus C5 (HAdV-C5) wt regarding attachment to human lung epithelial cells, endocytic uptake, endosome penetration and dependency on the E3 RING ubiquitin ligase Mind Bomb 1 for DNA uncoating at the nuclear pore complex. Atomic force microscopy measurements of single virus particles indicated that small changes in the genome length from 94% to 103% of HAdV-C5 have no major impact on physical and mechanical features of AdV vectors. In contrast, an HD-AdV-C5 with ∼30 kbp genome was slightly stiffer and less heat-resistant than the other particles, despite comparable entry and transduction efficiencies in tissue culture cell lines, including murine alveolar macrophage-like Max-Planck-Institute (MPI)-2 cells. Together, our in vitro studies reinforce the use of HD-AdV vectors for effective single round gene delivery. The results illustrate how physical properties and cell entry behavior of single virus particles can provide functional information for anticipated therapeutic vector applications.

Strengthening the relationship between intractable plantar keratosis and human papillomavirus.

The aim of the study was to determine the presence of human papillomavirus (HPV) in patients with intractable plantar keratosis (IPK) by comparing the histopathological findings of biopsies. A prospective, observational, and concordance study was carried out. Three different specimens were taken from each IPK. A first punch was sent for histopathological examination, and a second punch and a superficial skin scraping were both sent for HPV  polymerase chain reaction (PCR) and type determination. A total of 51 patients were included. From the histopathological examination, it was determined that 35 (68.6%) samples were diagnosed as warts and 16 (31.3%) as keratosis. However, the presence of HPV was confirmed by PCR in 49 (96.1%) and in 42 (82.4%) samples obtained by punch and superficial scraping, respectively. In the 49 PCR-positive samples, the most common HPV types were HPV1, HPV2, HPV27, HPV57, and HPV65, accounting for 81.6% of the samples. In conclusion, this study demonstrates that HPV infection and IPK lesions are very closely related. Although we cannot confirm that HPV is the cause of the development of IPK, the high prevalence of HPV observed in these lesions calls for a change to the procedures for managing IPK.

Reparación percutánea de insuficiencia mitral primaria con técnica borde a borde: primer reporte de caso en Uruguay / Percutaneous edge-to-edge repair of primary mitral regurgitation: first case report in Uruguay / Correção percutânea de regurgitação mitral primária com técnica "edge-to-edge": primeiro caso reportado em Uruguai

La insuficiencia mitral (IM) es una enfermedad frecuente. La degeneración mixomatosa es la principal causa de IM primaria en los países desarrollados. Si no se corrige, conduce a la disfunción ventricular y a la insuficiencia cardíaca congestiva, con elevada morbimortalidad. La cirugía de reparación valvular es el tratamiento recomendado en la IM primaria severa y sintomática. En los pacientes con alto riesgo quirúrgico las opciones terapéuticas son limitadas. El surgimiento de la reparación percutánea borde a borde ha permitido ofrecer alternativas terapéuticas para estos pacientes, y se han demostrado buenos resultados. Se presenta el caso clínico de un paciente añoso con IM primaria severa. Por su elevado riesgo quirúrgico se optó por realizar reparación percutánea con técnica borde a borde, con excelentes resultados clínicos y ecocardiográficos. Se trata del primer reporte de caso de estas características en nuestro país.

Mitral regurgitation (MR) is a common disease. Myxomatous degeneration is the main cause of primary MR in developed countries. If not corrected, it leads to ventricular dysfunction and congestive heart failure, with high morbidity and mortality. Valve repair surgery is the recommended treatment for severe and symptomatic primary MR. In patients with high surgical risk, therapeutic options are limited. The emergence of edge-to-edge percutaneous repair has made it possible to offer therapeutic alternatives for these patients, and good results have been demonstrated. We present the clinical case of an elderly patient with severe primary MR. Due to his high surgical risk, it was decided to perform percutaneous repair with edge-to-edge technique, with excellent clinical and echocardiographic results. It is the first case report of these characteristics in our country.

A regurgitação mitral (RM) é uma doença frequente. A degeneração mixomatosa é a principal causa de RM primária em países desenvolvidos. Se não for corrigido, leva à disfunção ventricular e insuficiência cardíaca congestiva, com alta morbimortalidade. A cirurgia de reparo valvular é o tratamento recomendado na RM primária grave. Em pacientes com alto risco cirúrgico, as opções terapêuticas são limitadas. O surgimento do reparo percutâneo com plicatura dos segmentos é uma opção terapêutica alternativa, com bons resultados demonstrados. Apresentamos o caso clínico de um paciente doente por RM primária grave. Devido ao seu alto risco cirúrgico, optou-se pela correção percutânea com técnica "edge-to-edge", com excelentes resultados clínicos e ecocardiográficos. Este é o primeiro caso publicado com a técnica em Uruguai.

Oral squamous cell carcinomas and oral potentially malignant disorders: A Latin American study.

OBJECTIVE: To determine the frequency of oral squamous cell carcinoma (OSCC) associated or not with oral potentially malignant disorders (OPMD), and the epidemiological profile and traditional risk factors in Latin America. METHODS: A retrospective observational study was conducted in 17 Latin American centres. There were included cases of OSCC, analysing age, gender, OSCC and their association with previous OPMD. Clinicopathological variables were retrieved. The condition of sequential-OSCC versus OSCC-de novo (OSCC-dn) was analysed concerning the aforementioned variables. Quantitative variables were analysed using Student's t-test, and qualitative variables with chi-square. RESULTS: In total, 2705 OSCC were included with a mean age of 62.8 years old. 55.8% were men. 53.75% of the patients were smokers and 38% were common drinkers. The lateral tongue border was the most affected site (24.65%). There were regional variations in OPMD, being leukoplakia the most frequent. Of the overall 2705 OSCC cases, 81.4% corresponded to OSCC-dn, while s-OSCC were 18.6%. Regarding lip vermillion SCC, 35.7% corresponded to de novo lip SCC and 64.3% were associated with previous OPMD. CONCLUSIONS: In Latin America, OSCC-dn seems to be more frequent with regional variations of some clinical and histopathological features. Further prospective studies are needed to analyse this phenomenon.

TransOrbital NeuroEndoscopic Surgery for Biopsy of the Left Cavernous Sinus: A Literature Review, Case Report, and Cadaveric Proof of Concept.

The aim of this report is to describe TransOrbital NeuroEndoscopic Surgery (TONES) as a safe alternative for obtaining a cavernous sinus (CS) biopsy. We describe this technique in a patient with a diffuse large B cell lymphoma mimicking Tolosa-Hunt's syndrome. Articles were gathered querying PubMed, Embase, and Scopus databases with terms related to a "transorbital neuroendoscopic approach." The literature search was performed by two independent authors (N.L.F. and J.R.), with inconsistencies resolved by the senior author (M.M.D.V.). After screening abstracts for relevance, full-length articles were reviewed for pertinent variables. A comparison was conducted with the illustrative case of a 69-year-old woman who presented to the emergency department with vertigo, ophthalmoplegia, and diplopia for 2 months. A brain magnetic resonance imaging revealed an infiltrative lesion at the left CS. A presumptive diagnosis of Tolosa-Hunt syndrome was made, but a confirmatory biopsy was performed using TONES. Based on our cadaveric study, literature review, and case report, the TONES approach was safe, effective for tissue diagnosis, and associated with minor morbidity and reduced hospital stay. Additional prospective studies are required to study its viability and safety in a larger group of patients.

Is ultrasonography accurate for the diagnosis of gallbladder polyps? A review of cholecystectomy specimens from patients diagnosed with gallbladder polyps over a 14-years period.

INTRODUCTION: Incidence of gallbladder polyps is 0,3-12%. It is important to differentiate pseudopolyps (cholesterol polyps, adenomyomatosis, inflammatory polyps), which do not have the capacity to become malignant, from true polyps (adenomas and adenocarcinomas). The main risk factors for malignancy are >6-10 mm, growth, sessile morphology, Indian ethnicity and primary sclerosing cholangitis. Ultrasound is the gold standard for diagnosis. Most polyps diagnosed by ultrasound are pseudopolyps. The main objective of this study is to analyse whether ultrasound is accurate for diagnosing true polyps in patients undergoing surgery for this reason. METHODS: Retrospective observational study with prospective data entry of patients undergoing elective cholecystectomy for gallbladder polyps from 2007 to 2021. Surgery was indicated in symptomatic patients and in those with risk factors. The study has been approved by the Clinical Research Ethics Committee of our hospital. RESULTS: We included 124 patients in our study. An elective laparoscopic cholecystectomy was performed in all of them. The mean age was 55,4 years and 61% were women. Of all patients, 65% were symptomatic at diagnosis. Only 3 patients had true polyps (2,4%). All of them were tubular adenomas. The rest of patients were false positives (97,6%). The adenoma size was 11, 6 and 5 mm, respectively. The surgical indication was due to polyp size or due to associated biliary symptoms. CONCLUSION: Ultrasonography is not accurate for the diagnosis of gallbladder polyps. Validation of other complementary tests for the diagnosis of gallbladder polyps in asymptomatic patients could be relevant to avoid unnecessary surgeries.

Adenovirus core protein V reinforces the capsid and enhances genome release from disrupted particles.

Out of the three core proteins in human adenovirus, protein V is believed to connect the inner capsid surface to the outer genome layer. Here, we explored mechanical properties and in vitro disassembly of particles lacking protein V (Ad5-ΔV). Ad5-ΔV particles were softer and less brittle than the wild-type ones (Ad5-wt), but they were more prone to release pentons under mechanical fatigue. In Ad5-ΔV, core components did not readily diffuse out of partially disrupted capsids, and the core appeared more condensed than in Ad5-wt. These observations suggest that instead of condensing the genome, protein V antagonizes the condensing action of the other core proteins. Protein V provides mechanical reinforcement and facilitates genome release by keeping DNA connected to capsid fragments that detach during disruption. This scenario is in line with the location of protein V in the virion and its role in Ad5 cell entry.

Cardiovascular health worsening in patients with autoimmune rheumatological diseases during the COVID-19 pandemic.

Rheumatic autoimmune diseases are associated with a myriad of comorbidities. Of particular importance due to their morbimortality are cardiovascular diseases. COVID-19 greatly impacted the world population in many different areas. Patients with rheumatic diseases had to face changes in their healthcare, in addition to unemployment, a decrease in physical activity, social isolation, and lack of access to certain medications. This review summarizes the impact of COVID-19 pandemic on cardiovascular risk factors, comorbidities, and unhealthy behaviors in patients with rheumatic inflammatory autoimmune diseases, particularly focused on rheumatoid arthritis and systemic lupus erythematosus. Searches were carried out in MEDLINE/PubMed and Scopus from August to December 2022. Four reviewers screened the title and abstract of retrieved records. Potentially eligible reports were then reviewed in full text. Differences were reconciled by either consensus or discussion with an external reviewer. During the COVID-19 pandemic, patients with rheumatic diseases showed an increase in the prevalence of mental health disorders (43.2-57.7%), reduced physical activity (56.8%), and a worsening in eating behaviors. Alcohol intake increased (18.2%), especially in early phases of the pandemic. Smoking prevalence decreased (28.2%). Dyslipidemia and hypertension showed no changes. The pandemic and lockdown affected rheumatic patients not only in disease-related characteristics but in the prevalence of their cardiovascular comorbidities and risk factors. Lifestyle changes, such as healthy eating, physical activity, and optimal management of their rheumatic diseases and comorbidities, are essential to manage the long-lasting consequences of the COVID-19 outbreak. Key Points • During the COVID-19 pandemic, anxiety, depression, sedentarism, obesity, and a worsening in eating behaviors increased. •Patients with rheumatic diseases and comorbidities have worse clinical outcomes and a higher cardiovascular disease burden than those without them. •Comparative studies are necessary to precisely elucidate the pandemic's impact on the prevalence of cardiovascular disease, risk factors, and comorbidities in patients with rheumatoid arthritis and systemic lupus erythematosus.

Unusual Corneal Sarcoidosis Manifestations.

AIM: To document atypical presenting forms of ocular sarcoidosis at the corneal level. METHODS: Case report. RESULTS: A 63-year-old woman presented multiple uncommon unilateral primary corneal conditions as manifestation of ocular sarcoidosis, including peripheral ulcerative keratitis, sterile corneal infiltrate (corneal granuloma), and sterile infiltrates related to a corneal foreign body, requiring medical and surgical management to control the inflammatory symptoms and to preserve the integrity of the eyeball. An excisional biopsy of a nodule in the temporal conjunctiva was performed under topical anesthesia. Histological analysis revealed a non-caseating granuloma, confirming the diagnosis of ocular sarcoidosis. CONCLUSION: When thinking of ocular involvement in patients with ocular sarcoidosis, it is essential to remember that manifestations such as peripheral ulcerative keratitis, sterile corneal infiltrate, and sterile foreign body-related infiltrates may be presentations of this disease.

NEDD4-1 deficiency impairs satellite cell function during skeletal muscle regeneration

BACKGROUND: Satellite cells are tissue-specific stem cells primarily responsible for the regenerative capacity of skeletal muscle. Satellite cell function and maintenance are regulated by extrinsic and intrinsic mechanisms, including the ubiquitin-proteasome system, which is key for maintaining protein homeostasis. In this context, it has been shown that ubiquitin-ligase NEDD4-1 targets the transcription factor PAX7 for proteasome-dependent degradation, promoting muscle differentiation in vitro. Nonetheless, whether NEDD4-1 is required for satellite cell function in regenerating muscle remains to be determined. RESULTS: Using conditional gene ablation, we show that NEDD4-1 loss, specifically in the satellite cell population, impairs muscle regeneration resulting in a significant reduction of whole-muscle size. At the cellular level, NEDD4-1-null muscle progenitors exhibit a significant decrease in the ability to proliferate and differentiate, contributing to the formation of myofibers with reduced diameter. CONCLUSIONS: These results indicate that NEDD4-1 expression is critical for proper muscle regeneration in vivo and suggest that it may control satellite cell function at multiple levels.

Utilidad de la tomografía de coherencia óptica como guía en el tratamiento del síndrome coronario agudo: reporte de un caso / Utility of optical coherence tomography to guide treatment in acute coronary syndromes: case report / Utilidade da tomografia de coerência óptica como guia no tratamento da síndrome coronariana aguda: relato de um caso

La tomografía de coherencia óptica (OCT) es una técnica de imagen endovascular con elevada resolución espacial que permite evaluar las diferentes estructuras que componen la pared de las arterias coronarias, caracterizar morfológicamente la placa aterosclerótica y establecer el mecanismo fisiopatológico subyacente en los síndromes coronarios agudos (SCA). Se presenta el caso clínico de un paciente con infarto agudo de miocardio, donde la OCT evidenció que la reducción de la luz arterial estaba determinada principalmente por la presencia de trombo, a la vez que demostró una disrupción endotelial (ruptura de placa) como mecanismo fisiopatológico subyacente. Se adoptó una estrategia invasivo-conservadora, donde finalmente no se implantó stent. La información surgida de la OCT en este caso particular fue fundamental en la toma de decisiones.

Optical coherence tomography (OCT) is an endovascular imaging technique with high spatial resolution. It allows to evaluate the different structures that compose coronary arteries' wall, morphologically characterize atherosclerotic plaques and establish the underlying pathophysiological mechanism in acute coronary syndromes (ACS). The case of a patient with acute myocardial infarction is presented, in which OCT showed that the reduction of arterial lumen was determined mainly by the presence of thrombus, while also demonstrated endothelial disruption (plaque rupture) as the underlying pathophysiological mechanism. An invasive-conservative strategy was adopted and finally stent was not implanted. The information that emerged from the OCT in this particular case was fundamental in decision-making.

A tomografia de coerência óptica (OCT) é uma técnica de imagem endovascular com alta resolução espacial que permite a avaliação das diferentes estruturas que compõem a parede das artérias coronárias, a caracterização morfológica da placa aterosclerótica e o estabelecimento do mecanismo fisiopatológico subjacente de síndrome coronariana aguda (SCA). Apresentamos o caso clínico de um paciente com enfarte agudo do miocárdio, onde a OCT mostrou que a redução do lúmen arterial foi determinada principalmente pela presença de trombo, ao mesmo tempo que demonstrou uma ruptura endotelial (ruptura da placa) como causa fisiopatológica subjacente. Adotou-se uma estratégia invasiva-conservadora, onde finalmente o stent não foi implantado. As informações obtidas da OCT neste caso específico foram fundamentais na tomada de decisão.

Transgenerational Tolerance to Salt and Osmotic Stresses Induced by Plant Virus Infection.

Following pathogen infection, plants have developed diverse mechanisms that direct their immune systems towards more robust induction of defense responses against recurrent environmental stresses. The induced resistances could be inherited by the progenies, rendering them more tolerant to stressful events. Although within-generational induction of tolerance to abiotic stress is a well-documented phenomenon in virus-infected plants, the transgenerational inheritance of tolerance to abiotic stresses in their progenies has not been explored. Here, we show that infection of Nicotiana benthamiana plants by Potato virus X (PVX) and by a chimeric Plum pox virus (PPV) expressing the P25 pathogenicity protein of PVX (PPV-P25), but not by PPV, conferred tolerance to both salt and osmotic stresses to the progeny, which correlated with the level of virulence of the pathogen. This transgenerational tolerance to abiotic stresses in the progeny was partially sustained even if the plants experience a virus-free generation. Moreover, progenies from a Dicer-like3 mutant mimicked the enhanced tolerance to abiotic stress observed in progenies of PVX-infected wild-type plants. This phenotype was shown irrespective of whether Dicer-like3 parents were infected, suggesting the involvement of 24-nt small interfering RNAs in the transgenerational tolerance to abiotic stress induced by virus infection. RNAseq analysis supported the upregulation of genes related to protein folding and response to stress in the progeny of PVX-infected plants. From an environmental point of view, the significance of virus-induced transgenerational tolerance to abiotic stress could be questionable, as its induction was offset by major reproductive costs arising from a detrimental effect on seed production.

Factors associated with lesion detection in colonoscopy among different indications.

BACKGROUND AND OBJECTIVE: Different factors may influence colonoscopy performance measures. We aimed to analyze procedure- and endoscopist-related factors associated with detection of colorectal lesions and whether these factors have a similar influence in the context of different colonoscopy indications: positive fecal immunochemical test (+FIT) and post-polypectomy surveillance colonoscopies. METHODS: This multicenter cross-sectional study included adults aged 40-80 years. Endoscopists (N = 96) who had performed ≥50 examinations were assessed for physician-related factors. Adenoma detection rate (ADR), adenomas per colonoscopy rate (APCR), advanced ADR, serrated polyp detection (SDR), and serrated polyps per colonoscopy rate (SPPCR) were calculated. RESULTS: We included 12,932 procedures, with 4810 carried out after a positive FIT and 1967 for surveillance. Of the 96 endoscopists evaluated, 43.8% were women, and the mean age was 41.9 years. The ADR, advanced ADR, and SDR were 39.7%, 17.7%, and 12.8%, respectively. Adenoma detection rate was higher in colonoscopies after a +FIT (50.3%) with a more than doubled advanced ADR compared to non-FIT procedures (27.6% vs. 13.0%) and similar results in serrated lesions (14.7% vs. 13.5%). Among all the detection indicators analyzed, withdrawal time was the only factor independently related to improvement (p < 0.001). Regarding FIT-positive and surveillance procedures, for both indications, withdrawal time was also the only factor associated with a higher detection of adenomas and serrated polyps (p < 0.001). Endoscopist-related factors (i.e., weekly hours dedicated to endoscopy, annual colonoscopy volume and lifetime number of colonoscopies performed) had also impact on lesion detection (APCR, advanced ADR and SPPCR). CONCLUSIONS: Withdrawal time was the factor most commonly associated with improved detection of colonic lesions globally and in endoscopies for + FIT and post-polypectomy surveillance. Physician-related factors may help to address strategies to support training and service provision. Our results can be used for establishing future benchmarking and quality improvement in different colonoscopy indications.

Aplicaciones terapéuticas del eculizumab / Therapeutic applications of eculizumab

Introducción: El eculizumab es un anticuerpo monoclonal de tipo IgG diseñado para el tratamiento de la hemoglobinuria paroxística nocturna (HPN), en el que su diana farmacológica forma parte del sistema del complemento. Su mecanismo de acción ha permitido implementarlo en el tratamiento de enfermedades huérfanas, como el síndrome urémico hemolítico atípico (SUHa), trastorno del espectro de la neuromielitis óptica (TENMO) y miastenia gravis, cuya incidencia, es baja. Asimismo, es viable en el tratamiento de Guillain Barré y el síndrome antifosfolípido catastrófico (CAPS). Objetivo: Evidenciar aplicaciones terapéuticas del eculizumab y beneficios más significativos en algunos padecimientos. Materiales y métodos: Se realizó búsqueda bibliográfica en el periodo 2010-2021, en bases de datos: Google Scholar, Science Direct, PubMed y Scielo, utilizando como palabra clave "eculizumab". Posteriormente, se afinó la búsqueda utilizando palabras claves asociadas a enfermedades tratadas con este medicamento. Resultados: Se identificó el mecanismo de acción del fármaco y su efecto sobre la patogénesis de hemoglobinuria paroxística nocturna, síndrome urémico atípico, miastenia gravis generalizada refractaria, trastorno del espectro de la neuromielitis óptica, síndromes antifosfolípidos catastrófico y Guillain-Barré. Conclusiones: El eculizumab tiene una alta seguridad y capacidad para tratar y disminuir síntomas de diversas enfermedades que involucran el sistema del complemento.

Introduction: Eculizumab is an IgG type monoclonal antibody designed to treat paroxysmal nocturnal hemoglobinuria (PNH) and its pharmacological target is a member of the complement system. Its mechanism of action has permitted its use in the treatment of orphan diseases such as atypical hemolytic uremic syndrome (aHUS), neuromyelitis optic spectrum disorder (NMOSD), and myasthenia gravis, all of which have a low incidence. Likewise, eculizumab is a viable treatment for Guillain Barré and catastrophic antiphospholipid syndrome (CAS). Objective: To describe the therapeutic applications of eculizumab and its most significant benefits in some illnesses. Materials and methods: A bibliographic search was carried out during the 2010-2021 period in Google Scholar, Science Direct, PubMed and Scielo databases using the keyword eculizumab. Then, the search was refined by using keywords associated with diseases treated with this medication. Results: The mechanism of action of the antibody and its effect on the pathogenesis of paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, refractory generalized myasthenia gravis, neuromyelitis optic spectrum disorder, catastrophic antiphospholipid syndrome, and Guillain Barré were identified. Conclusions: Eculizumab has high safety and capacity in treating and diminishing symptoms of diverse illnesses, which involve the complement system.

A Liquid Biopsy Signature for the Detection of Patients With Early-Onset Colorectal Cancer.

BACKGROUND & AIMS: Early-onset colorectal cancer (EOCRC) is a distinct clinical and molecular entity with poor survival outcomes compared with late-onset CRC. Although the incidence of EOCRC is rising, current CRC screening strategies have several limitations in diagnostic performance for EOCRC. In view of this clinical challenge, novel and robust biomarkers for detection of EOCRC are necessary. The aim of this study was to develop a circulating micro RNA (miRNA) signature for the diagnosis of patients with EOCRC. METHODS: A systematic discovery approach by analyzing a large, publicly available, noncoding RNA expression profiling dataset (GSE115513) was used. A panel of miRNAs was identified, which was subsequently validated in blood samples from patients with EOCRC in 2 independent cohorts (n = 149) compared with controls (n = 110) and pre/postoperative plasma specimens (n = 22) using quantitative reverse-transcription polymerase chain reaction assays. RESULTS: In the discovery phase, 4 miRNAs were found to be expressed in blood samples. A combination signature of these 4 miRNAs (miR-193a-5p, miR-210, miR-513a-5p, and miR-628-3p) yielded an area under the curve of 0.92 (95% confidence interval, 0.85-0.96) for identification of EOCRC in the training cohort. The miRNA panel performance was then confirmed in an independent validation cohort (area under the curve, 0.88; 95% confidence interval, 0.82-0.93). Moreover, the miRNA panel robustly identified patients with early-stage EOCRC (P < .001). The decreased expression of miRNAs in postsurgery plasma specimens indicated their tumor specificity. CONCLUSIONS: Our novel miRNA signature for the diagnosis of EOCRC has the potential to identify patients with EOCRC with high accuracy for clinical application in the noninvasive diagnosis of EOCRC.

Estudio de la amiloidosis cardíaca por cardiorresonancia / Cardiac amyloidosis study by cardioresonance / Estudo da amiloidose cardíaca por cardiorressonância

Dada su epidemiología, la amiloidosis cardíaca se ha vuelto un desafío diagnóstico del siglo XXI. La resonancia cardíaca se ha transformado en una herramienta diagnóstica y pronóstica fundamental en la práctica clínica diaria. En este artículo de revisión resumimos el conocimiento, primero abordando la técnica en sí, desde protocolos generales a específicos para su diagnóstico. Posteriormente, y tomando estas herramientas, sistematizamos la utilidad diagnóstica, pronóstica y terapéutica, con base en la practicidad y evidencia científica más recientes, otorgando la posibilidad de utilizar y abordar desde un correcto diagnóstico por imagen diferentes aspectos de esta enfermedad prevalente.

Given its epidemiology, cardiac amyloidosis has become a diagnostic challenge of the twenty-first century. Cardiac resonance has become a fundamental diagnostic and prognostic tool in daily clinical practice. In this review article we summarize the knowledge, first addressing the technique itself, from general to specific protocols for its diagnosis. Subsequently, and taking this tool we systematize the diagnostic, prognostic, and therapeutic utility, based on the most recent practicality and scientific evidence, granting the possibility of using and addressing from a correct diagnostic imaging different aspect of this prevalent disease.

Dada a sua epidemiologia, a amiloidose cardíaca tornou-se um desafio do século XXI. A ressonância cardíaca tornou-se uma ferramenta diagnóstica e prognóstico fundamental na prática clínica diária. Neste artigo de revisão resumimos primeiro o conhecimento abordando a própria técnica, desde protocolos gerais até específicos para seu diagnóstico. Posteriormente, e tomando essa ferramenta sistematizamos a utilidade diagnóstica, prognóstica e terapêutica, com base na praticidade e evidência científica mais recentes, concedendo a possibilidade de utilização e abordagem de uma imagem diagnóstica correta de diferentes aspectos desta doença prevalente.

Impact of COVID-19 in pediatric oncology care in Latin America during the first year of the pandemic.

BACKGROUND: The ongoing coronavirus 2019 disease (COVID-19) pandemic strained medical systems worldwide. We report on the impact on pediatric oncology care in Latin American (LATAM) during its first year. METHOD: Four cross-sectional surveys were electronically distributed among pediatric onco-hematologists in April/June/October 2020, and April/2021 through the Latin American Society of Pediatric Oncology (SLAOP) email list and St Jude Global regional partners. RESULTS: Four hundred fifty-three pediatric onco-hematologists from 20 countries responded to the first survey, with subsequent surveys response rates above 85%. More than 95% of participants reported that treatment continued without interruption for new and active ongoing patients, though with disruptions in treatment availability. During the first three surveys, respondents reported suspensions of outpatient procedures (54.2%), a decrease in oncologic surgeries (43.6%), radiotherapy (28.4%), stem cell transplants (SCT) (69.3%), and surveillance consultations (81.2%). Logistic regression analysis showed that at the beginning of the first wave, participants from countries with healthcare expenditure below 7% were more likely to report a decrease in outpatient procedures (odds ratio [OR]: 1.84, 95% CI: 1.19-2.8), surgeries (OR: 3, 95% CI: 1.9-4.6) and radiotherapy (OR: 6, 95% CI: 3.5-10.4). Suspension of surveillance consultations was higher in countries with COVID-19 case fatality rates above 2% (OR: 3, 95% CI: 1.4-6.2) and SCT suspensions in countries with COVID-19 incidence rate above 100 cases per 100,000 (OR: 3.48, 95% CI: 1.6-7.45). Paradoxically, at the beginning of the second wave with COVID-19 cases rising exponentially, most participants reported improvements in cancer services availability. CONCLUSION: Our data show the medium-term collateral effects of the pandemic on pediatric oncology care in LATAM, which might help delineate oncology care delivery amid current and future challenges posed by the pandemic.