Reavaliação do nirmatrelvir/ritonavir para o tratamento de pacientes com COVID-19 não hospitalizados e com alto risco de doença grave / Revalidation of nirmatrelvir/ritonavir for the treatment of patients with COVID-19 who are not hospitalized and with a high risk of serious illness

INTRODUÇÃO: Pacientes com fatores de risco como idade avançada, imunodepressão, obesidade e doenças cardiovasculares têm risco aumentado de internação, intubação e morte. De acordo com dados brasileiros, o risco de morte por covid-19 aumenta com o número de fatores de risco que o paciente apresenta, sendo igual a 17% em pacientes com 2 fatores de risco e 76% na presença de 8 fatores de risco. Além disso, mesmo aqueles pacientes que sobrevivem a uma internação em terapia intensiva frequentemente enfrentam sequelas e representam alto custo para o sistema público. O medicamento nirmatrelvir associado ao ritonavir têm o objetivo de prevenir internações, complicações e morte. Ele é indicado para pacientes com Covid-19 leve a moderada, não hospitalizados, até 5 dias do início dos sintomas. Apesar dos avanços da vacinação no Brasil, evidências sobre a falha vacinal em idosos e imunodeprimidos destacam a importância da disponibilidade de alternativas terapêuticas para essas populações. O presente relatório teve por objetivo avaliar evidências sobre a efetividade do tratamento em pacientes vacinados com alto risco de agravamento da doença. PERGUNTA: O medicamento nirmatrelvir/ritonavir é eficaz, seguro e custo-efetivo para pacientes com covid19 leve a moderada não hospitalizados vacinados que apresentam alto risco de agravamento da doença? EVIDÊNCIAS CLÍNICAS: Resultados obtidos a partir de estudos observacionais de mundo real confirmaram os resultados do ensaio clínico do medicamento nirmatrelvir/ritonavir, demonstrando que o tratamento de pacientes de grupos de risco é capaz de reduzir o risco de desfechos desfavoráveis como internação e óbito entre cerca de 50% e 70%, inclusive entre pacientes previamente vacinados. ANÁLISE DE IMPACTO ORÇAMENTÁRIO: A análise de impacto orçamentário do relatório de recomendação do nirmatrelvir/ritonavir foi atualizada considerando-se o cenário atual da pandemia no Brasil. De acordo com a nova análise, o uso do nirmatrelvir/ritonavir por pacientes com idade ≥ 65 anos e imunossuprimidos com idade ≥ 18 anos, resultaria em uma economia de recursos de R$ 408.957.111,38 em 5 anos. Ressalta-se, no entanto, que devido à dinâmica de difícil previsão da pandemia, este montante está sujeito à incerteza. Considerando-se a análise realizada anteriormente no relatório de recomendação, pode-se concluir que o montante economizado se reduz proporcionalmente à redução do número de casos da doença na população alvo. CONSIDERAÇÕES FINAIS: De acordo com as evidências atualmente disponíveis, o uso do nirmatrelvir/ritonavir é efetivo e seguro para pacientes com covid-19 leve a moderada não hospitalizados vacinados que apresentam alto risco de agravamento da doença. O impacto orçamentário está sujeito a incertezas já que o número de casos da doença no horizonte temporal da análise é de difícil previsão. RECOMENDAÇÃO PRELIMINAR DA CONITEC: Diante do exposto, os membros do Comitê de Medicamentos da Conitec, em sua 16ª Reunião Extraordinária, realizada no dia 1º de novembro de 2023, deliberaram que a matéria fosse disponibilizada em Consulta Pública com recomendação preliminar favorável à incorporação no SUS do nirmatrelvir/ritonavir para o tratamento de pacientes com Covid-19 não hospitalizados com idade a partir de 65 anos ou pacientes imunossuprimidos a partir de 18 anos de idade. Os membros do Comitê concordaram na manutenção da indicação de uso, não havendo ampliação do público-alvo, justificada pela restrição orçamentária, considerando que há incremento de custo da aquisição da tecnologia, ainda que haja economia de recursos ao serem evitadas internações e óbitos. CONSULTA PÚBLICA: Das nove contribuições recebidas, cinco contribuições foram de cunho técnico-científico e quatro contribuições de experiência ou opinião. Todas as contribuições concordaram com a recomendação preliminar da Conitec de incorporar o nirmatrelvir/ritonavir. Duas contribuições técnico-científicassugeriram ampliação da população elegível ao tratamento com o medicamento com a inclusão de indicação para pacientes com taxa de filtração glomerular menor que 30 ml/min/1,73m2 e de pacientes adultos com asma grave independentemente da faixa etária. Uma contribuição técnico-científica enviada pela empresa fabricante do medicamento expressou sua concordância com e solicitou a inclusão de informaçõea adicionais no relatório. As contribuições de experiência ou opinião ressaltaram a eficácia e segurança do medicamento para a população alvo. RECOMEDAÇÃO FINAL DA CONITEC: Diante do exposto, os membros do Comitê de Medicamentos, presentes na 126ª Reunião Ordinária da Conitec, realizada no dia 01 de fevereiro de 2024, deliberaram, por unanimidade, após reavaliação, manter a incorporação do nirmatrelvir/ritonavir, no SUS, para o tratamento da Covid-19 nos seguintes grupos de pacientes com sintomas leves a moderados, que não requerem oxigênio suplementar, independentemente do status vacinal: a) imunocomprometidos com idade ≥ 18 anos; b) com idade ≥ 65 anos. Foi assinado o registro de deliberação nº 874/2024. DECISÃO: manter a incorporação, no âmbito do Sistema Único de Saúde - SUS, de nirmatrelvir/ritonavir para o tratamento da Covid-19 para pacientes com sintomas leves a moderados, que não requerem oxigênio suplementar, independentemente do status vacinal e com idade igual ou superior a 65 anos ou imunocomprometidos com idade igual ou superior a 18 anos, publicada no Diário Oficial da União nº 46, seção 1, página 54, em 07 de março de 2024.

Amputación de pie diabético: Manejo de los factores predisponentes, criterios para su indicación y manejo post quirúrgico. Aprobada por resolución exenta N° 293.Orientación técnica / Diabetic foot amputation: management of predisposing factors, criteria for indication and post-surgical management. Approved by exempt resolution N° 293. Technical guidance

El presente documento entrega a los equipos de salud contenidos para la estandarización del manejo de los factores predisponentes de la amputación, criterios para su indicación y manejo post quirúrgico. Si bien este documento hace alusión a una condición de salud en particular, es fundamental tener presente que la atención de salud de las personas con enfermedades crónicas se basa en la integralidad del cuidado, el que considera a la persona en el contexto de su multimorbilidad, por lo que el abordaje presentado se utiliza con fines operativos.

Acute Aortic Regurgitation due to Aortic Dissection Limited to the Sinus of Valsalva, Which Was Found at the Time of Surgery: a Case Report / 日本心臓血管外科学会雑誌

Aortic dissection is one cause of acute aortic regurgitation, and transthoracic echocardiography and computed tomography are useful for diagnosis. We report a case of intraoperatively discovered acute aortic regurgitation caused by aortic dissection limited to the sinus of Valsalva. The patient was a 71-year-old man who regularly visited his local doctor for hypertension and diabetes mellitus. He visited the doctor with a week-long history of cough and dyspnea, and was referred to our hospital due to acute congestive heart failure. We diagnosed severe acute aortic regurgitation as the cause of the heart failure, but the aortic root dissection was not detected by transthoracic echocardiography or plain computed tomography. Since his heart failure progressively worsened even with intensive medical therapy, urgent surgery was decided on the 6th day after hospitalization. Intraoperatively, we noted that the aortic dissection was limited to the sinus of Valsalva, and had induced aortic regurgitation due to dissected and separated aortic commissure. We changed the surgical procedure from aortic valve replacement to the Bentall procedure (Piehler method). Postoperatively, the patient was intubated for 7 days and stayed in the ICU for 14 days due to treatment for pneumothorax and organizing pneumonia. He was successfully transferred to a rehabilitation hospital on the 35th postoperative day. Acute aortic regurgitation caused by aortic dissection limited to the sinus of Valsalva is rare, so we report the case based on literature reviews and as a heart team.

Neutralization Testing–based Immunogenicity Analysis of Recent Prevalent Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Sublineages

Although WHO declared the end of the public health emergency for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), XBB lineages continue to evolve and emerge globally. In particular, XBB.1.5 and XBB.1.16 are raising concerns because of their high immune evasion, leading to apprehensions regarding vaccine efficacy reduction and potential reinfection. We aimed to investigate the COVID-19 outbreak in Korea and predict the likelihood of reinfection by testing neutralizing activity against live viruses from the S clade and 19 Omicron sublineages.We found a significant risk of infection with the currently prevalent XBB lineage for individuals who were either vaccinated early or infected during the initial Omicron outbreak. Vaccinated individuals were better equipped than unvaccinated individuals to produce neutralizing antibodies for other SARS-CoV-2 variants upon infection. Therefore, unvaccinated individuals do not easily develop neutralizing activity against other variants and face the highest risk of reinfection by the XBB lineage. Our study provides important information to facilitate the development of strategies for monitoring populations that would be the most susceptible to new COVID-19 outbreaks.

Changes in Structural Covariance among Olfactory-related Brain Regions in Anosmia Patients

Anosmia, characterized by the loss of smell, is associated not only with dysfunction in the peripheral olfactory system but also with changes in several brain regions involved in olfactory processing. Specifically, the orbitofrontal cortex is recognized for its pivotal role in integrating olfactory information, engaging in bidirectional communication with the primary olfactory regions, including the olfactory cortex, amygdala, and entorhinal cortex. However, little is known about alterations in structural connections among these brain regions in patients with anosmia. In this study, highresolution T1-weighted images were obtained from participants. Utilizing the volumes of key brain regions implicated in olfactory function, we employed a structural covariance approach to investigate brain reorganization patterns in patients with anosmia (n=22) compared to healthy individuals (n=30). Our structural covariance analysis demonstrated diminished connectivity between the amygdala and entorhinal cortex, components of the primary olfactory network, in patients with anosmia compared to healthy individuals (z=-2.22, FDR-corrected p=0.039). Conversely, connectivity between the orbitofrontal cortex—a major region in the extended olfactory network—and amygdala was found to be enhanced in the anosmia group compared to healthy individuals (z=2.32, FDR-corrected p=0.039). However, the structural connections between the orbitofrontal cortex and entorhinal cortex did not differ significantly between the groups (z=0.04, FDR-corrected p=0.968). These findings suggest a potential structural reorganization, particularly of higher-order cortical regions, possibly as a compensatory effort to interpret the limited olfactory information available in individuals with olfactory loss.

Atypical Presentation of Elsberg Syndrome Caused by Herpes Simplex Virus Type 2 Infection

Elsberg syndrome is a rare disease of lumbosacral myeloradiculitis, mostly caused by herpes simplex virus type 2 (HSV-2). It frequently has concomitant myelitis, and immunocompromised patients can be fatal with ascending myelitis. Since anti-viral agents might lead to good recovery, clinicians need to be suspicious for conditions of cauda equina syndrome. Detection of viral DNA from cerebrospinal fluid ensures the diagnosis. We report a case of Elsberg syndrome caused by HSV-2 and are to delineate the clinical and radiologic spectrum.

Risk factors for SARS-CoV-2 transmission during a movie theater outbreak in Incheon in the Republic of Korea, November 2021: a retrospective study

Objectives@#We examined factors contributing to the transmission of an acute respiratory virus within multi-use facilities, focusing on an outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a movie theater in the Republic of Korea. @*Methods@#This retrospective cohort study involved a descriptive analysis of 48 confirmed cases. Logistic regression was applied to a cohort of 80 theater attendees to identify risk factors for infection. The infection source and transmission route were determined through gene sequencing data analysis. @*Results@#Of the 48 confirmed cases, 35 were theater attendees (72.9%), 10 were family members of attendees (20.8%), 2 were friends (4.2%), and 1 was an employee (2.1%). Among the 80 individuals who attended the 3rd to 5th screenings of the day, 35 became infected, representing a 43.8% attack rate. Specifically, 28 of the 33 third-screening attendees developed confirmed SARS-CoV-2, constituting an 84.8% attack rate. Furthermore, 11 of the 12 cases epidemiologically linked to the theater outbreak were clustered monophyletically within the AY.69 lineage. At the time of the screening, 35 individuals (72.9%) had received 2 vaccine doses. However, vaccination status did not significantly influence infection risk. Multivariate analysis revealed that close contacts had a 15.9-fold higher risk of infection (95% confidence interval, 4.37–78.39) than casual contacts. @*Conclusion@#SARS-CoV-2 transmission occurred within the theater, and extended into the community, via a moviegoer who attended the 3rd screening during the viral incubation period after contracting the virus from a family member. This study emphasizes the importance of adequate ventilation in theaters.

Severe Liver Dysfunction after Donor Lymphocyte Infusion for Relapsed Multiple Myeloma / 대한소화기학회지

Donor lymphocyte infusion (DLI) is performed to augment an anti-tumor immune response or ensure donor stem cells remain engrafted following allogeneic stem cell transplantation but may induce graft-versus-host disease (GVHD) involving skin, intestine, and liver. Although hepatic involvement of GVHD can manifest as mild to severe hepatitis, few reports have mentioned acute severe liver dysfunction with encephalopathy. We experienced a case of acute severe liver dysfunction with semicoma after DLI in a patient with relapsed multiple myeloma following allogeneic stem cell transplantation, in whom chronic viral hepatitis B had been suppressed by antiviral treatment. The patient recovered after high-dose glucocorticoid administration based on an assessment of hepatic GVHD.Clinicians should be aware of the possibility of this catastrophic hepatic complication after DLI in hematologic disorders.

Allergen sensitization trajectories in children with respiratory and allergic diseases

Purpose@#There is a lack of a report about the trajectories of allergen sensitization, although it is important to understand the change of allergen sensitization to manage allergic disease. This study aimed to analyze the change and trajectories of allergen sensitization in children with respiratory and allergic diseases. @*Methods@#From 2006 to 2020, children with respiratory and allergic diseases or screened for allergic sensitization were evaluated. We visualized the alterations and the trajectories of allergen sensitization using stacked area graphs, box plots, and Sankey diagrams. @*Results@#A total of 2,804 subjects were included, and allergic rhino-conjunctivitis was diagnosed in 1,931 children (68.9%). The mean age for the first test was 4.1 years, and that for the second test was 6.5 years. Children sensitized to class 1 food allergen before age 5 showed sensitizations more for other allergens and at a younger age after age 5 than children who were not. The atopic tendency continued once it had been obtained before the early school age in the persistence or the new development of sensitization. @*Conclusion@#Allergen sensitization has changed over time and has shown different patterns according to age. Its trajectory has taken a wide variety of courses in children with respiratory and allergic diseases until the early school age. These changes reflect the allergic diseases and socio-environmental characteristics of children and adolescents.

Rapidly growing juvenile xanthogranuloma in an adult: a case report

Juvenile xanthogranuloma is a benign tumor made up of non-Langerhans histiocytes that predominantly occurs in infancy and early childhood. Juvenile xanthogranuloma can be differentiated from xanthoma by the distribution of the lesions and the absence of lipid abnormalities. It usually develops on the trunk and upper and lower extremities. Histologically, xanthogranulomas show a mixed cellular dermal infiltration with histiocytes, lymphocytes, eosinophils and Touton-type multinucleated giant cells. Classically, juvenile xanthogranuloma is a disease that largely affects infants and children. We describe a rare case of juvenile xanthogranuloma that suddenly developed in the axillary region of a male adult.

Novel surgical use of electrosurgical tip cleaners in subdermal excision for axillary osmidrosis

Background@#Axillary osmidrosis is a disease characterized by axillary malodor. The conventional treatment method of subdermal excision uses Metzenbaum scissors. Recently, subdermal excision using the Versajet system was introduced. However, it is an expensive surgical tool, and a recent study demonstrated a higher frequency of axillary skin necrosis with the Versajet. We propose a novel, cost-effective, and safe subdermal excision method that utilizes an electrosurgical tip cleaner (ETC). @*Methods@#Our retrospective cohort study included 27 patients who underwent subdermal excision from June 2012 to November 2021. The patients were classified into three groups according to the surgical method: Metzenbaum scissors, Versajet, and ETC. The operation time, hospitalization cost, and postoperative complications were investigated. @*Results@#The number of patients in the Metzenbaum scissors, Versajet, and ETC groups was seven, eleven, and nine, respectively. The mean operation time and hospitalization cost were significantly different among the three groups (P<0.05). The longest mean operation time was observed in the Metzenbaum scissors group (112.9±23.6 minutes), followed by the ETC and Versajet groups (76.4±27.1 and 64.2±24.8 minutes, respectively). The most expensive method was the Versajet ($2,346.1±517.7), followed by the ETC and Metzenbaum scissors ($1,391.8±317.7 and $1,279.6±287.5, respectively). No postoperative complications were observed. @*Conclusions@#The ETC is a novel method of subdermal excision, comparable to Metzenbaum scissors or Versajet. Therefore, it is recommended for situations where it is necessary to consider both the time and cost of surgery.

Effects of Posterior Oblique Sling Activation on Gluteus Maximus Muscle Activity during Prone Hip Extension Exercises in Healthy Male Individuals

Purpose@#The purpose of this study was to investigate the effects of posterior oblique sling activation on the muscle activities of the gluteus maximus (GM), multifidus (MF), and biceps femoris (BF) during three different prone hip extension exercises in healthy male individuals. @*Methods@#Twenty healthy subjects participated in this study. An electromyography device was used to measure the muscle activities of the GM, MF, and BF. Each subject was asked to perform three different prone hip extensions as follows: [1) Prone hip extension with knee flexion + hip abduction 30°; PHE1, 2) Prone hip extension with knee flexion + hip abduction 30° and shoulder abduction 125°; PHE2, 3) Prone hip extension with knee flexion + hip abduction 30° and shoulder abduction 125° with 1kg loading; PHE3, in random order. A oneway repeated measures analysis of the variance and a Bonferroni post hoc test were used to analyze the results. The statistical signifi-cance was set at α= 0.01. @*Results@#The muscle activity of the GM was significantly different between the three positions (Padj < 0.01). The muscle activity of the GM was significantly greater during PHE3 compared with PHE1 and PHE2 (Padj < 0.01). The BF muscle activity was significantly lower during PHE3 compared with PHE1 and PHE2 (Padj < 0.01). There was no significant difference in the muscle activity of the MF (Padj < 0.01). The ratio of the muscle activity (ratio= GM/BF) during PHE3 was significantly greater compared to PHE1 and PHE2 (Padj < 0.01). @*Conclusion@#The GM activity and GM/BF ratio during the PHE3 exercise were significantly greater compared to that during PHE1 and PHE2. Therefore, the PHE3 exercise could be recommended as a selectively effective GM activation exercise while decreasing the muscle activity of the BF.

Evaluation of the mechanical properties of current biliary self-expandable metallic stents: axial and radial force, and axial force zero border

Background/Aims@#Mechanical properties (MPs) and axial and radial force (AF and RF) may influence the efficacy and complications of self-expandable metallic stent (SEMS) placement. We measured the MPs of various SEMSs and examined their influence on the SEMS clinical ability. @*Methods@#We evaluated the MPs of 29 types of 10-mm SEMSs. RF was measured using a conventional measurement device. AF was measured using the conventional and new methods, and the correlation between the methods was evaluated. @*Results@#A high correlation in AFs was observed, as measured by the new and conventional manual methods. AF and RF scatterplots divided the SEMSs into three subgroups according to structure: hook-and-cross-type (low AF and RF), cross-type (high AF and low RF), and laser-cut-type (intermediate AF and high RF). The hook-and-cross-type had the largest axial force zero border (>20°), followed by the laser-cut and cross types. @*Conclusions@#MPs were related to stent structure. Hook-and-cross-type SEMSs had a low AF and high axial force zero border and were considered safest because they caused minimal stress on the biliary wall. However, the increase in RF must be overcome.

Intracellular Loop in the Brain Isoforms of Anoctamin 2 Channels Regulates Calcium-dependent Activation

Anoctamin 2 (ANO2 or TMEM16B), a calcium-activated chloride channel (CaCC), performs diverse roles in neurons throughout the central nervous system. In hippocampal neurons, ANO2 narrows action potential width and reduces postsynaptic depolarization with high sensitivity to Ca2+ at relatively fast kinetics. In other brain regions, including the thalamus, ANO2 mediates activity-dependent spike frequency adaptations with low sensitivity to Ca2+ at relatively slow kinetics. How this same channel can respond to a wide range of Ca2+ levels remains unclear. We hypothesized that splice variants of ANO2 may contribute to its distinct Ca2+ sensitivity, and thus its diverse neuronal functions. We identified two ANO2 isoforms expressed in mouse brains and examined their electrophysiological properties: isoform 1 (encoded by splice variants with exons 1a, 2, 4, and 14) was expressed in the hippocampus, while isoform 2 (encoded by splice variants with exons 1a, 2, and 4) was broadly expressed throughout the brain, including in the cortex and thalamus, and had a slower calcium-dependent activation current than isoform 1. Computational modeling revealed that the secondary structure of the first intracellular loop of isoform 1 forms an entrance cavity to the calcium-binding site from the cytosol that is relatively larger than that in isoform 2. This difference provides structural evidence that isoform 2 is involved in accommodating spike frequency, while isoform 1 is involved in shaping the duration of an action potential and decreasing postsynaptic depolarization. Our study highlights the roles and molecular mechanisms of specific ANO2 splice variants in modulating neuronal functions.

Antioxidant and anti-inflammatory activities of Lespedeza cuneata in Coal fly ash-induced murine alveolar macrophage cells

Lespedeza cuneata (LC) is a perennial plant used in herbal medicine to treat numerous diseases, including prostatic hyperplasia, diabetes, early atherosclerosis, and hematuria. Reference collections of bioactive compounds of LC are crucial for the determination of their pharmacological properties. However, little is known regarding its anti-oxidative and anti-inflammatory effects in alveolar macrophage (MH-S) cells. This study examined whether LC can inhibit reactive oxygen species and Coal fly ash (CFA) induced inflammation in MH-S cells. The anti-oxidative effects of LC were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays, anti-inflammatory effects were examined using nitric oxide (NO) assay, and cytotoxicity was analyzed using methyl thiazolyl tetrazolium assay. The expression of inflammatory cytokine genes was assessed through a reverse-transcription polymerase chain reaction. Our results revealed that LC exhibited high radical scavenging activity and a dose-dependent (7.8–1,000 μg/mL) inhibition of oxidation as compared to ascorbic acid and Trolox. It also inhibited CFA-induced NO production in MH-S cells. Moreover, it suppressed the CFA exposure-mediated expression of pro-inflammatory mediators and cytokines, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. These results suggest that LC is a potent antioxidant and anti-inflammatory agent that can be useful as a nutraceutical product.

Progress of Research on Gastrointestinal Flora in Screening, Diagnosis and Prognosis of Esophageal Cancer / 胃肠病学

Esophageal cancer is a common and poorly prognostic cancer, and early screening and early diagnosis arc the keys to improve the prognosis of patients. In recent years, more and more studies have shown that changes in gastrointestinal flora are associated with the occurrence, progression, recurrence, metastasis and chemotherapy resistance of esophageal cancer. This article mainly reviewed the changes of gastrointestinal flora in esophageal cancer patients and the progress of research on gastrointestinal flora in the screening, diagnosis and prognosis of esophageal cancer.

Estrategias de cambio de conducta y educación para la salud en personas adultas y mayores con multimorbilidad crónica. Orientación técnica / Behaviour change strategies and health education in adults and older people with chronic multimorbidity. Technical guidance

El abordaje actual de las enfermedades no transmisibles constituye un permanente desafío para los equipos de salud y para las personas que están en dicha situación. Estos cambios en la modalidad de atención habitual se vienen generando hace varios años en Chile, estas respuestas buscan potenciar desde la Atención Primaria de Salud (APS) y en todos los niveles de atención, un sistema de salud con enfoque de equidad, perspectiva de curso de vida, integralidad e intersectorialidad con el objetivo de satisfacer las necesidades de las personas de mantenerse saludables, sanos, y mejorar su estado de salud en caso de enfermedad. Este documento tiene por objetivo establecer requisitos para el diseño, ejecución y evaluación de estrategias educativas y de cambio de conducta en salud centradas en las personas adultas y mayores en situación de multi-morbilidad crónica, con enfoque en la construcción de conductas saludables.

Correlation of REG1A, Claudin 7 and Ki67 expressions with tumor recurrence and prognostic factors in superficial urothelial urinary bladder carcinomas

A?m: Superficial urothelial urinary bladder tumors are neoplasms that frequently recur and have a potential for invasion and metastasis. REG gene family is composed of various acute phase reactants, lectins, antiapoptotic factors, and growth factors that are effective on pancreatic island cells, neural cells, and epithelial cells. REG1A and REG1B are two forms of the human REG1 gene. It is reported that they are expressed in several cancers and are correlated with the prognosis of the patient. Claudins are integral transmembrane proteins that interconnect cells. However, their role in human tumorigenesis is extremely controversial. The aim of this study is to evaluate the relationship of REG1A, claudin 7 protein expressions, and Ki67 proliferation index in superficial urothelial urinary bladder tumors with well-known parameters of prognosis and tumor recurrence, and also to clarify whether these parameters are independent prognostic factors or not. Materials and Methods: A hundred and eleven patients diagnosed with superficial urothelial carcinoma between 2011 and 2016 years in our hospital and followed up in our urology clinic were included in this study. The slides prepared from paraffin blocks were immunohistochemically stained with REG1A, claudin 7, and Ki67 antibodies. Results: REG1A showed positive staining in 37 (33%) and negative staining in 74 (67%) of urothelial tumors. Claudin 7 was positive in 24 (22%) and negative in 87 (78%) cases. REG1A expression showed a positive correlation with tumor stage and tumor recurrence; a high Ki67 proliferation index was positively correlated with tumor stage and grade. The loss of claudin 7 expression was related to tumor recurrence. Besides, tumors with REG1A expression and claudin 7 loss had a shorter survival independent of recurrence. Conclus?on: In urothelial tumors, REG1A expression and loss of claudin 7 might be significant markers of prognosis that predict tumor recurrence.

Déficit de vitamina D en niños y adolescentes que reciben tratamiento antiepiléptico. Estudio descriptivo / Vitamin D deficiency in children and adolescents receiving antiepileptic treatment. Descriptive study

Resumen Introducción: la hipovitaminosis D es un problema prevalente en la población general y muy frecuente en niños; relacionado a diferentes patologías o factores como el uso de medicamento antiepilépticos (MAEs), principalmente aquellos inductores enzimáticos del citocromo P450, ampliamente relacionados con la salud ósea. Razón por la que este estudio busca determinar la distribución de insuficiencia de Vitamina D en niños tratados farmacológicamente para la epilepsia, así como establecer factores asociados basándose en características sociodemográficas, clínicas y terapéuticas. Metodología: estudio descriptivo, transversal, retrospectivo con 103 pacientes con epilepsia en manejo con MAEs, asistentes a la consulta de neuropediatría en un hospital de tercer nivel, se tomó información de las historias clínicas de niños entre 0 y 18 años durante enero del 2016 y junio del 2019. Se construyó un modelo multivariado en relación a la presencia de insuficiencia de vitamina D y valores normales de esta. Resultados: el 44,7% presentaron insuficiencia de vitamina D, mientras 6,8% de pacientes presentó deficiencia, de los cuales 4 tenían historia de fracturas. Se encontró asociación estadísticamente significativa con la insuficiencia en pacientes que residen en área rural (ORa=4,2 (IC95=1,3-13,4) p=0,013), pertenecen a nivel socio económico bajo (Ora=2,9 (IC95%=1,1-77) p=0,030) y padecen epilepsia refractaria (Ora=3,1 (IC95%=1-8,7) p=0,033). Conclusiones: la hipovitaminosis D es frecuente en paciente con epilepsia en manejo farmacológico con MAE. La insuficiencia se asoció con epilepsia refractaria, nivel socioeconómico bajo y provenir de área rural, por lo que se recomienda vigilancia rutinaria de los niveles de vitamina D y suplementación en aquellos pacientes con déficit. MÉD.UIS.2022;35(1): 71-9

Abstract Hypovitaminosis D is a prevalent problem in the general population and very common in children; related to different pathologies or factors such as the use of antiepileptic drugs (MAEs), mainly those enzymatic inducers of cytochrome P450, broadly related with bone health. Reason why this study seeks to determine the distribution of vitamin D insufficiency in children with epilepsy in pharmacological treatment and to establish associated factors based on sociodemographic, clinical, and therapeutic characteristics. Methodology: descriptive, cross- sectional, retrospective study with 103 patients with epilepsy in management with MAEs, attending the neuropaediatric consultation in a third-level hospital, information was taken from the medical records of children between 0 and 18 years of age during January 2016 and June 2019. A multivariate model was built in relation to the presence of vitamin D insufficiency and its normal values. Results: 44.7% of patients had vitamin D insufficiency, while 6.8% had deficiency, of which 4 had a history of fractures. A statistically significant association with insufficiency was found in patients residing in rural areas (ORa=4.2 (IC95=1.3-13.4) p=0.013), they belong to a low socio-economic level (Ora=2.9 (95% CI=1.1-77) p=0.030) and suffering from refractory epilepsy (Ora=3.1 (95% CI=1-8.7) p=0.033). Conclusions: hypovitaminosis D is frequent in a patient with epilepsy under pharmacological management with MAE. Insufficiency was associated with refractory epilepsy, low socioeconomic status and coming from rural areas, so routine monitoring of vitamin D levels is recommended in those patients with deficits. MÉD.UIS.2022;35(1): 71-9

Endocarditis infecciosa luego del implante de válvula aórtica por cateterismo / Infective Endocarditis after Transcatheter Aortic Valve Implantation

RESUMEN Introducción: La endocarditis infecciosa (EI) post implante percutáneo de válvula aórtica (TAVI) es poco frecuente, con una alta tasa de morbimortalidad. Métodos: Se analizaron 630 pacientes consecutivos con TAVI, de los cuales 6 (0,95%) presentaron EI. Resultados: Cuatro eran hombres, edad 81,3 ± 2,2 años, y todos sintomáticos. La fracción de eyección ventricular izquierda (FEVI) fue 56,8 ± 5,3%. Todos recibieron un implante exitoso y uno presentó regurgitación moderada. Dos requirieron marcapaso definitivo, a uno de ellos se le debió recolocar el cable a las 24 hs. La EI se presentó a los 63,5 ± 73,3 días (mediana de 35 días). El germen aislado fue un coco (+) en cuatro casos. En uno se observó una vegetación en el ecocardiograma transesofágico. Un paciente falleció dentro de los 30 días. El seguimiento fue a 23 ± 22 meses, ningún paciente presentó nuevos eventos o internaciones. En el eco Doppler la FEVI fue de 55,9 ± 4,6%, el gradiente medio 8,2 ± 1,8 mmHg y la velocidad pico de 1,8 ± 0,2 m/seg. Un paciente terminó una regurgitación moderada. Conclusiones: En esta serie de pacientes, la EI post TAVI fue poco frecuente y presentó una evolución favorable con el tratamiento antibiótico.

ABSTRACT Background: Infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI) is a rare complication with high morbidity and mortality. Methods: Of 630 consecutive patients undergoing TAVI, 6 (0.95%) presented IE. Results: Four patients were men, mean age was 81.3 ± 2.2 years and all the patients were symptomatic. Left ventricular ejection fraction (LVEF) was 56.8 ± 5.3%. The procedure was successful in all the patients and one presented moderate regurgitation. Two patients required definitive pacemaker and the lead had to be reimplanted 24 hours later in 1 patient. Time to IE was 63.5 ± 73.3 days (median 35 days). A Gram-positive coccus was isolated in four cases. One patient presented a vegetation on transesophagic echocardiography. One patient died within 30 days. During follow-up of 23 ± 22 months none of the patients presented new events or hospitalizations. On Doppler echocardiography, LVEF was 55.9 ± 4.6%, mean trans-aortic gradient was 8.2 ± 1.8 mm Hg and peak systolic velocity was 1.8 ± 0.2 m/s. One patient had moderate regurgitation. Conclusions: In this series of patients, IE after TAVI was uncommon and had a favorable course with antibiotic treatment.