TEMA CENTRAL: FACETAS DE LA MEDICINA • Evaluation of marker-based optical coherence tomography findings in diabetic macular edema treated with intravitreal ranibizumab therapy • Efectos del decúbito prono en síndrome de distrés respiratorio agudo secundario a COVID-19: Experiencia en un hospital de alta complejidad • Evaluación de la percepción de los participantes de un programa de entrenamiento con simulación in situ en un Centro de Paciente Crítico Adulto • Tendencias de la mortalidad por diabetes mellitus en Chile (1990-2020) • Mecanismos de acción de los probióticos en la inhibición de microorganismos cariogénicos • Tratamiento sistémico actual para cáncer de mama avanzado hormono-dependiente • Cien números de emergencias en Chile: desarrollo histórico y contexto en salud Caso clínico • Alteraciones extremas del sodio durante el periodo neonatal: presentación de dos casos. • Signo de la galleta Oreo®: revisión de la anatomía de un signo clásico radiológico a través de un caso clínico Comentario portada • Medicine - Gustav Klimt REVISTA MÉDICA E-ISSN: 2531-0186/ ISSN: 0716-8640 CLÍNICA LAS CONDES / VOL. 34 Nº 3 / MAYO-JUNIO 2023
2017 2016 2018 2019 2020 2021 2022 Nº Visitas Nº páginas visitadas LA VISIBILIDAD SE HA INCREMENTADO EN 20 VECES DESDE EL AÑO 2015 Accesos web INDEXADA DESDE EL 2019 EN EMERGING SOURCES CITATION INDEX (ESCI) DE WEB OF SCIENCE GROUP Emerging Sources Citation Index (ESCI) benefits the academic research ecosystem “ESCI has a positive effect on research assessment and it accelerates communication in the scientific community.” Early Insight on the ESCI: an overlay map-based bibliometric study Scientometrics, 18 March 2017 “Indexing in the ESCI will improve the visibility of a journal, provides a mark of quality, and is good for authors. We have already seen examples of institutions and funders suggesting publication in an ESCI listed journal, similar to what already takes places with other Web of Science databases.” James Hardcastle, Senior Manager, Product Analytics, Taylor & Francis 13 February 2017 10,000,000 9,000,000 8,000,000 7,000,000 6,000,000 5,000,000 4,000,000 3,000,000 2,000,000 1,000,000 0 Clínica Las Condes REVISTA MÉDICA Desde 1989 edición ininterrumpida REVISTA MÉDICA CLÍNICA LAS CONDES ESTÁ EN ELSEVIER Y SCIENCE DIRECT DESDE EL AÑO 2016 LAS ZONAS GEOGRÁFICAS CON MAYOR Nº DE VISITAS SON AMÉRICA LATINA Y EL SUR DE EUROPA 177 1.136.913 EDITORES GENERALES José Antonio Del Solar Renato Palma Ronald Youlton Jaime Arriagada Susana Benítez Patricio Burdiles Cynthia Argüello https://www.elsevier.es/es-revista-revista-medica-clinica-las-condes-202
183 ÍNDICE Revista Médica Clínica Las Condes - Bimestral “El contenido de los artículos publicados en esta revista no representa necesariamente la visión y política de Clínica Las Condes y, por lo tanto, es de exclusiva responsabilidad de sus autores”. Revista Médica CLC disponible en Elsevier: www.elsevier.es/revistamedicaclinicalascondes www.sciencedirect.com Revista Médica Clínica Las Condes / vol. 34 nº3 / Mayo - junio 2023 TEMA CENTRAL: FACETAS DE LA MEDICINA COMITÉ EDITORIAL EDITORIAL Comité Editorial ARTÍCULOS • Evaluación de hallazgos de tomografía de coherencia óptica basados en marcadores en edema macular diabético tratado con terapia intravítrea con ranibizumab - Yuliono Trika Nur Hasan y cols. • Efectos del decúbito prono en síndrome de distrés respiratorio agudo secundario a COVID-19: Experiencia en un hospital de alta complejidad - Paulina Vivanco-Aravena y cols. • Evaluación de la percepción de los participantes de un programa de entrenamiento con simulación in situ en un Centro de Paciente Crítico Adulto - Andrés Ferre y cols. • Tendencias de la mortalidad por diabetes mellitus en Chile (1990-2020) - Blas Vargas Contreras y col. • Mecanismos de acción de los probióticos en la inhibición de microorganismos cariogénicos - Yari Pablo López y cols. • Tratamiento sistémico actual para cáncer de mama avanzado hormono-dependiente - Benjamín Walbaum y cols. • Cien números de emergencias en Chile: desarrollo histórico y contexto en salud - Patricio Garrido-Mancilla CASOS CLÍNICOS • Alteraciones extremas del sodio durante el periodo neonatal: presentación de dos casos - Alba Pérez-Pérez y cols. • Signo de la galleta Oreo®: revisión de la anatomía de un signo clásico radiológico a través de un caso clínico - Julián Muñoz Durán y cols. COMENTARIO PORTADA • Gustav Klimt, “Medicina”- Comité Editorial GUÍA DE PUBLICACIÓN PARA AUTORES ...185-185 ...186-186 ...187-194 ...195-203 ...204-209 ...210-215 ...216-223 ...224-234 ...235-241 ...242-246 ...247-251 ...252-252 ...253-256
184 INDEX Revista Médica Clínica Las Condes is a bimonthly publication. “The content of the manuscripts in this journal does not necessarily represent the vision and policy of Clínica Las Condes and therefore, is the responsability of its authors”. Revista Médica CLC in Elsevier: www.elsevier.es/revistamedicaclinicalascondes www.sciencedirect.com MAIN TOPIC: FACETS OF MEDICINE Revista Médica Clínica Las Condes / vol. 34 nº3 / May-Jun 2023 EDITORIAL BOARD EDITORIAL Editorial Committee ARTICLES • Evaluation of marker-based optical coherence tomography findings in diabetic macular edema treated with intravitreal ranibizumab therapy - Yuliono Trika Nur Hasan et al. • Effects of prone position in acute respiratory distress syndrome secondary to COVID-19: Experience in a high complexity hospital - Paulina Vivanco-Aravena et al. • Evaluation of participants’ perception of an in situ simulation training program in an adult critical care center - Andrés Ferre et al. • Diabetes mellitus mortality trends in Chile (1990-2020) - Blas Vargas Contreras et al. • Probiotic action mechanisms in the inhibition of cariogenic microorganisms - Yari Pablo López et al. • Current systemic treatment for advanced stage hormone dependent breast cancer - Benjamín Walbaum et al. • One hundred emergency numbers in Chile: Historical development and health context - Patricio Garrido-Mancilla CLINICAL CASES • Extreme sodium alterations during the neonatal period: two case reports - Alba Pérez-Pérez et al. • Oreo® cookie sign: Anatomic review of a classic radiologic sign through a case report - Julián Muñoz Durán et al. COVER PAGE COMMENTARY • Gustav Klimt, “Medicine”- Editorial Committee GUIDE FOR AUTHORS ...185-185 ...186-186 ...187-194 ...195-203 ...204-209 ...210-215 ...216-223 ...224-234 ...235-241 ...242-246 ...247-251 ...252-252 ...253-256
185 Revista Médica de Clínica Las Condes (RMCLC) es el órgano de difusión científica de Clínica Las Condes, hospital privado chileno de alta complejidad. Esta revista, de edición bimestral, publica revisiones bibliográficas de la literatura biomédica, actualizaciones, experiencias clínicas derivadas de la práctica médica, artículos originales y casos clínicos, en todas las especialidades de la salud. Cada número se estructura en torno a un tema central, el cual es organizado por un editor invitado especialista en ese ámbito de la medicina. Los artículos desarrollan este tema central en detalle, considerando sus diferentes perspectivas y son escritos por autores altamente calificados, provenientes de diferentes instituciones de salud, tanto chilenas como extranjeras. Todos los artículos son sometidos a un proceso de revisión por pares. El objetivo de RMCLC es ofrecer una instancia de actualización de primer nivel para los profesionales de la salud, además de constituir una herramienta de apoyo para la docencia y de servir como material de estudio para los alumnos de medicina de pre- y postgrado y de todas las carreras de la salud. Revista Médica Clínica Las Condes is the scientific journal of Clínica las Condes, a Chilean high complexity private hospital. This is a biomedical review journal and is published every two months. It also publishes original studies and clinical or radiological cases, in all the medical specialties. Each edition has a main topic, planned by the editorial board, with an invited editor who is a specialist on the topic. Different articles are developed in detail around the principal topic, and written by highly qualified authors, from different Chilean or foreign health institutions. All the articles are submitted to peer review. The aim of Revista Médica Clinica Las Condes is to offer a high level of up-to-date knowledge for health professionals, and to be a teaching tool for undergraduates and graduate medical students. Objetivos de la Revista Médica de Clínica Las Condes Objetivos de la Revista Médica de Clínica Las Condes aims & scope Editora General Cynthia Argüello Guerra, MD, MBA, MPH. Academic Direction, Clinica Las Condes, Santiago, Chile. Editora Científica y Ejecutiva Claudia Hurtado Riveros, Biochemist, PhD. Oncologic and Molecular Genetics Laboratory, Academic Direction, Clínica Las Condes, Santiago, Chile. Comité Editorial Alessandra Cassana Abad, MD, PhD(c). Medical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, Chile. Rodrigo Gil Dib, MD. Assistant Professor, Universidad de Chile, Santiago, Chile. Rogelio González Pérez, MD. High Risk Unit, Hospital San José, Santiago, Chile. Comité Científico María Elena Alvarado Bretón, MD, MPH, PhD. Instituto de Neurocirugía Dr. Alfonso Asenjo, Providencia, Chile. Javier Brahm Barril, MD. Head of Gastroenterology, Hospital Clínico Universidad de Chile, Santiago, Chile. Ruben D. Carrasco, MD, PhD. Harvard Medical School, Boston; Dana-Farber Cancer Institute, Boston, United States of America. Fanny Cortés Monsalve, MD. Rare Disease Center, Clínica Las Condes, Santiago, Chile. Raul J. Gazmuri, MD, PhD. Resuscitation Institute, Rosalind Franklin University of Medicine and Sciences, Chicago, United States of America. Josep M. Grau Junyet, MD. Universitat de Barcelona, Barcelona, Spain. Carlos Guillén Astete, MD. Hospital Universitario Ramón y Cajal, Madrid. Universidad Europea de Madrid, Madrid, Spain. Julia Guerrero Peralta, MD, PhD. Department of Internal Medicine North, Faculty of Medicine - Clinical Hospital. University of Chile, Santiago, Chile. Carlos S. Kase, MD. Department of Neurology, Emory University, Atlanta, United States of America. Marcelo Molina Salinas, MD. Instituto Traumatologico Dr Teodoro Gebauer Weisser, Santiago, Chile. Justo Padilla Ygreda., MD. Instituto Nacional de Salud del Niño, San Borja, Lima, Peru. Fanny Petermann-Rocha, PhD. Faculty of Medicine, Universidad Diego Portales, Santiago, Chile. [COMITÉ EDITORIAL REVISTA MÉDICA CLÍNICA LAS CONDES 2023] REVISTA MÉDICA CLÍNICA LAS CONDES https://www.journals.elsevier.com/revista-medica-clinica-las-condes REPRESENTANTE LEGAL Sr. Ignacio Tapia EDITORA GENERAL carguello@clinicalascondes.cl Fono: (+562) 2610 3153 EDITORA CIENTÍFICA/EJECUTIVA churtado@clinicalascondes.cl Fono: (+562)2610 3153 DISEÑO Y DIAGRAMACIÓN Macarena Márquez A. Email: infocalicoo@gmail.com
186 [REV. MED. CLIN. CONDES - 2023; 34(3) 186-186] REVISTA MÉDICA CLÍNICA LAS CONDES https://www.journals.elsevier.com/revista-medica-clinica-las-condes Nuestra edición mayo-junio 2023 está dedicada a ser un repertorio de la diversidad de la medicina de hoy. Ser editores de la Revista Médica Clínica Las Condes nos da el privilegio de avizorar el trabajo de nuestros colegas a lo largo de cuatro continentes. Tenemos la posibilidad de visualizar cuales temas, tanto clásicos como emergentes, preocupan y ocupan a los sistemas y profesionales de la salud según sus diferentes realidades locales y regionales. Ser una revista cuya misión es servir de órgano difusor del conocimiento científico médico y contribuir como instrumento de enseñanza para la educación de profesionales de la salud, nos permite trabajar a lo largo del espectro amplio de temáticas que, hoy en día, define el ejercicio de la medicina. Es así como orgullosamente recibimos manuscritos tan diversos como el de Hasan et al. quienes evalúan los resultados de la inyección intravitreal de ranibizumab de sus pacientes en Indonesia mientras Vivanco et al. nos comentan el efecto del decúbito prono en pacientes con síndrome de distrés respiratorio agudo en un hospital de alta complejidad. Ferre et al. nos presentan la percepción de los participantes de un programa de entrenamiento de simulación in situ realizado en un centro de pacientes críticos. Por su lado, Vargas y Gálvez EDITORIAL Comite Editorial analizan las tendencias de mortalidad por diabetes mellitus en Chile, dando luces de las fluctuaciones que han tenido en los últimos treinta años y aportando valiosa información para su enfrentamiento en el futuro. Desde México, Pablo et al. destacan los mecanismos de inhibición de microorganismos cariogénicos que manifiestan algunos probióticos. Asimismo, Walbaum et al. nos ponen al día con el estado del arte del tratamiento de los cánceres de mama hormono-dependientes. Garrido, por su parte, nos da el contexto histórico del desarrollo de los números de emergencia en Chile. Esta edición, además, trae dos artículos de casos clínicos: Pérez et al. nos presentan dos casos clínicos de alteraciones de sodio en el departamento de Neonatología de un hospital español y desde Colombia, Muñoz Durán et al. nos recuerdan cómo el uso de un signo radiológico clásico puede apoyar el diagnóstico del derrame pericárdico en centros que no cuenten con ecografía o tomografía. Esperamos que el espectro de temas presentes en esta edición sea un aporte a nuestros lectores. Facetas de la medicina
187 INFORMACIÓN DEL ARTÍCULO Historia del Artículo: Recibido: 09 01 2023 Aceptado: 05 04 2023 Key words: Edema, Macular; Retinopatía Diabética; Choroid Disease; Sub Retinal Fluid; anti-VEGF; Ranibizumab. Palabras clave: Edema Macular Diabético; Diabetic Retinopathies; Enfermedad Coroides; Líquido Sub-Retiniano; Anti-VEGF; Ranibizumab. RESUMEN Objetivo: Evaluar los efectos a corto plazo de la inyección intravítrea de ranibizumab (IVR) sobre los cambios visuales y estructurales en el edema macular diabético. Pacientes y métodos: Estudio retrospectivo que incluyó 108 ojos de 74 pacientes con edema macular diabético en los que se inyectó tres veces IVR 3 veces con intervalos de un mes. Las capas retinal y coroidea, así como el área de líquido subretiniano, se midieron al inicio del estudio y durante 3 meses de tratamiento. Se investigó la correlación entre los cambios estructurales y la agudeza visual. Resultados: En general, la mayoría de las capas de la retina tendieron a disminuir después del tratamiento. La resolución del líquido subretiniano siguió siendo relativamente superior para predecir el resultado de la inyección de ranibizumab. Además, encontramos que la reducción del grosor de la capa de fotorreceptores tuvo la mejor estimación de la ganancia de agudeza visual. Conclusión: La recuperación neural de de la capa de fotorreceptores se asocia con una mejor mejora visual. La segmentación individual de la retina sería beneficiosa para monitorear y evaluar el tratamiento con ranibizumab en el edema macular diabético. Evaluation of marker-based optical coherence tomography findings in diabetic macular edema treated with intravitreal ranibizumab therapy Evaluación de hallazgos de tomografía de coherencia óptica basados en marcadores en edema macular diabético tratado con terapia intravítrea con ranibizumab Yuliono Trika Nur Hasana,b #, Zulvikar Syambani Ulhaqc,d # , Muhammad A’raaf Sirojan Kusumaa, Maharani Oryza Sativaa, Azka Faradiba Anjani Hulayyaa, Badariyatud Dinib, Lola Ayu Istifianie, Syafrizal Aji Pamungkasf, Lina Puspita Hutasoitb. a Faculty of Medicine and Health Science, Maulana Malik State Islamic University. Malang, Indonesia. b Department of Ophthalmology, Karsa Husada General Hospital. Batu, Indonesia. c Research Center for Pre-Clinical and Clinical Medicine, National Research and Innovation Agency Republic of Indonesia. Cibinong, Indonesia. d Laboratory of Developmental Disorders and Toxicology, Center for Promotion of International Education and Research, Kyushu University. Fukuoka, Japan. e Department of Nutrition, Faculty of Health Sciences, Brawijaya University. Malang, Indonesia. f Al-Falah Social Fund Foundation Clinic (YDSF). Malang, Indonesia. ORIGINAL ARTICLE [REV. MED. CLIN. CONDES - 2023; 34(3) 187-194] REVISTA MÉDICA CLÍNICA LAS CONDES https://www.journals.elsevier.com/revista-medica-clinica-las-condes Autor para correspondencia Correo electrónico: zulvikar.syambani.ulhaq@brin.go.id; zulhaq@kedokteran.uin-malang.ac.id https://doi.org/10.1016/j.rmclc.2023.04.001 e-ISSN: 2531-0186/ ISSN: 0716-8640/© 2023 Revista Médica Clínica Las Condes. Este es un artículo Open Access bajo la licencia CC BY-NC-ND (http://creativecommons.org/licenses/by-nc-nd/4.0/). # Both authors contributed equally and shared first authorships to this manuscript
188 INTRODUCTION Diabetes macular edema (DME) remains a major complication of diabetic retinopathy (DR) and is one of the most frequent causes of visual impairment among productive-age individuals1. Considering the large number of diabetic patients in the population, early identification and proper treatment for patients with DME are crucial due to the potential impact on our public health system and patient quality of life. The pathomechanism of DME is multifactorial. Nevertheless, mounting evidence indicates that it develops as a result of an increase in retinal vascular hyperpermeability due to the upregulation of vascular endothelial growth factor (VEGF)2,3. Although vascular dysfunction in the retina and choroid is the main contributor to the pathogenesis of DR and DME, retinal neurodegeneration seems independently associated with the severity of DR4-6. Hence, evaluating both vascular and neuronal changes are important in order to assess disease progression and therapeutic responses. Laser photocoagulation has been the gold standard for the treatment of DME for several decades1,7. Today, however, intravitreal anti-VEGF injection is considered the first-line therapy for DME due to its significant effect on visual outcomes and tolerability risks. Additionally, it has been previously described that different anatomical responses to anti-VEGF therapy are observed in each morphologic subtype of DME1. Thus, identifying distinctive structural changes could be useful for the ophthalmologist in managing and monitoring DME evolution. With the recent advancement of imaging techniques and technologies, the evaluation of morphological changes in the retina can be easily performed over time. In particular, spectral-domain optical coherence tomography (SD-OCT) can quantitatively examine intraretinal damage in DME8,9. Moreover, retinal layer changes are often used to monitor the effectiveness of anti-VEGF therapy for DME10,11. This study, therefore, aims to measure retABSTRACT Purpose: To evaluate the short-term effects of intravitreal ranibizumab (IVR) injection on visual and structural changes in diabetic macular edema (DME). Patients and methods: A retrospective study including 108 eyes of 74 patients with DME in which IVR injection was conducted three times at one-month intervals. Retinal and choroidal layers, as well as the subretinal fluid area, were measured at baseline and during 3 months of treatment. The correlation between structural changes and visual acuity was investigated. Results: In general, most of the retinal layers tended to decrease after treatment. Resolution of subretinal fluid remained relatively superior in predicting the outcome of ranibizumab injection. In addition, we found that reduction of photoreceptor layer (PRL) thickness provided the best estimation of visual acuity gain. Conclusion: Neural recovery in PRL is associated with better visual improvement. Individual retinal segmentation would be beneficial for monitoring and evaluating ranibizumab treatment in DME. inal and choroidal layer thickness, as well as subretinal fluid areas during a three-month follow-up to determine a possible association between visual acuity and structural changes in DME patients treated with intravitreal ranibizumab (IVR) injection, in addition to the identification of a promising biomarker for treatment response. PATIENTS AND METHODS Study design and ethical consideration This is a retrospective single-center observational study. This study followed the tenets of the Declaration of Helsinki and was approved by the Ethics Committee of Karsa Husada General Hospital (Ref. No. 072/251/102.13/2022). Data were obtained from the ophthalmology clinic database in Karsa Husada General Hospital, Batu, Indonesia. Patients and intravitreal ranibizumab injection One hundred eight eyes belonging to 74 patients were treated with three doses of IVR injection, at one month intervals, for DME treatment at the Karsa Husada General Hospital ophthalmology clinic between January 2021 and December 2022. The inclusion criteria were the presence of DME before therapy, no history of ocular surgery/treatment within the previous 10 weeks, and no macular involvements (such as retinal vein occlusion and age-related macular degeneration). Before injection and at monthly follow-ups, patients underwent comprehensive ophthalmologic examinations, including measurement of best-corrected visual acuity (BCVA), intraocular pressure (IOP) evaluation with Goldmann applanation tonometry, as well as biomicroscopic examination of the anterior segment and funduscopy. Intravitreal injections were conducted monthly with 0.5 mg/0.05 mL ranibizumab (Patizra, Novartis). A topical antibiotic was applied after the IVR injection for six days. [REV. MED. CLIN. CONDES - 2023; 34(3) 187-194]
189 [Evaluation of marker-based optic coherence tomography findings in diabetic macular edema treated with intravitreal... - Yuliono Trika Nur Hasan et al.] Structural outcomes evaluated by optical coherence tomography (OCT) Both horizontal A and vertical B scan images of the macular region concentrated at the fovea were examined using spectral domain optical coherence tomography (SD-OCT) (Spectralis, Heidelberg Engineering, Heidelberg, Germany). Structural outcomes were examined by evaluating retinal layer thickness, choroidal layer thickness and subretinal fluid area. Individual retinal layer and choroidal layer thickness were measured manually according to the literature4,12. Briefly, the OCT image was loaded into ImageJ. The scale bar provided in the OCT image was used as a standard reference. The retinal layer thickness was then manually measured by outlining each retinal layer in the parafoveal ring (the average retinal thickness in the superior, inferior, nasal, and temporal regions was used), while choroidal layer thickness was quantified in the central fovea (Figure 1A). Basically, the scale bar was converted into the distance in pixels. Then unknown distance in pixels outlined in each layer will be automatically quantified to the corresponding scale by ImageJ. The subretinal fluid area was evaluated by manually outlining the areas using ImageJ software (Figure 1A). The outer choroid layer thickness (OCLT, yellow line) was measured from the inner boundary of the choroid scleral junction to the innermost point of the choroidal large blood vessel observed closest to the fovea centralis. The inner choroidal layer thickness (ICLT, red line) was obtained by subtracting the OCLT from the total choroid layer thickness (TCLT, white line). Statistical analysis All continuous variables were expressed as the mean ± standard deviation, while categorical variables were expressed as percentages. The variables between the two groups (baseline vs. final visit) were compared using either an independent or dependent t-test, depending on the nature of the data. Correlations between visual and structural outcomes were evaluated using Pearson correlation analysis. r >0.5 was considered positively correlated and r = 0.3 to 0.5 as moderate positively correlated. The values of retinal changes were used to generate ROC (receiver operating characteristic) curves using the GraphPad Prism version 9 in order to determine the area under the curve (AUC). The optimal cut-off for each parameter was determined using Youden’s index, and the corresponding sensitivity and specificity for the cut-off were also quantified. Individual clinical factors were subjected to univariate linear analysis and were subsequently entered into the multivariate analysis in a backward stepwise manner. The criterion Figure 1. Retina and choroid segmentation (A) Retina and choroid segmentation using SD-OCT; (B) Structural changes before and after treatment in patients who received 3 doses of IVR injections due to DME; (C) Receiver operating characteristics (ROC) curve analysis. ROC curve of INL, ONL, TRLT, ORLT, and FA for the assessment of ranibizumab effectiveness. FA, fluid area; IRLT, inner retinal layer thickness; ORLT, outer retinal layer thickness; TRLT, total retinal layer thickness; ICLT, inner choroidal layer thickness; OCLT, outer choroidal layer thickness; TCLT, total choroidal layer thickness; INL, inner retina layer; ONL, outer retina layer.
190 for retention in the multivariate model was p <0.05. All statistical analyses were 2-tailed with a significance threshold of p <0.05 calculated with SPSS version 25. RESULTS Demographic and clinical characteristics Seventy-four patients with DME, including 32 males and 42 females, were examined and followed up for 3 months. The baseline characteristics are depicted in table 1. The mean age of patients with DME was 53.17 ± 8.42 years old, with a duration of diabetes of 9.95 ± 7.21 years. All patients were treated with ranibizumab (Patizra, Novartis) monotherapy. The mean baseline visual acuity (LogMAR BCVA) of the treated eye was 0.93 ± 0.61 and decreased by an average of 0.65 ± 0.51 at month three (p = 0.0007) (Table 2). Structural changes evaluated by SD-OCT during three months of ranibizumab treatment The total retinal layer thickness (TRLT) decreased from 410.40 ± 115.00 μm at baseline to 358.20 ± 79.52 μm after three months of ranibizumab treatment (p = 0.010, table 2, figure 1B). Further examination indicated that only the outer retinal layer thickness (ORLT) was significantly lower at the final visit (p = 0.015, table 2). Although each individual retinal layer thickness (RLT) tended to decrease after IVR injection within three months of treatment, the thickness changed more significantly within the inner nuclear layer (INL, p = 0.007) and outer nuclear layer (ONL, p = 0.007) (Table 2). In contrast to RLT, no changes were observed in the choroidal layer thickness (CLT) (Table 2). In addition, we observed that three months of ranibizumab treatment effectively decreased the fluid area in the subretinal region (p = 0.0005, table 2). ROC analysis was performed in parameters with significant changes after ranibizumab injection in order to identify a possible biomarker for treatment evaluation. The changes in the subretinal fluid area were relatively superior to the other parameters (AUC=0.76, cut-off =78,257 with sensitivity of 84% and specificity of 68%, p = 0.001) (Figure 1C). Table 1. Demographic and clinical characteristics Characteristics Value Sex (male/female) 32/42 Age, y, mean ± SD 53.17 ± 8.42 Duration of diabetes mellitus, y, mean ± SD 9.95 ± 7.21 LogMAR BCVA at baseline, mean ± SD 0.93 ± 0.61 IOP at baseline, mean ± SD 14.32 ± 4.17 Laterality, R/L 64/44 RBG, mg/dL, mean ± SD 152.17 ± 75.07 HbA1c, %, mean ± SD 8.96 ± 1.01 BCVA, best-corrected visual acuity; IOP, intraocular pressure; logMAR, logarithm of the minimum angle of resolution; L, left; R, right; SD, standard deviation; RBG, random blood glucose, HbA1c, hemoglobin A1c. Table 2. Visual acuity and structural changes evaluated by SD-OCT Parameters Baseline Final visit p-val LogMAR BCVA 0.93 ± 0.61 0.65 ± 0.51 0.0007 Retinal Layer (μm) Retinal Nerve Fiber Layer (RNFL) 18.12 ± 9.68 13.57 ± 9.59 0.249 Ganglion Cell Layer (GCL) 52.14 ± 13.59 51.74 ± 14.08 0.884 Inner Plexiform Layer (IPL) 45.99 ± 13.38 43.09 ± 10.64 0.257 Inner Nuclear Layer (INL) 59.03 ± 17.70 50.98 ± 11.25 0.007 Outer Plexiform Layer (OPL) 20.13 ± 7.79 17.34 ± 6.29 0.076 Outer Nuclear Layer (ONL) 128.60 ± 95.38 81.42 ± 32.41 0.007 Photoreceptor Layer (PRL) 78.01 ± 49.40 63.43 ± 25.27 0.085 Total Retinal Layer Thickness (TRLT) 410.40 ± 115.00 358.20 ± 79.52 0.010 -Inner Retinal Layer Thickness (IRLT) 182.40 ± 38.32 166.40 ± 33.46 0.072 -Outer Retinal Layer Thickness (ORLT) 228.00 ± 98.08 184.50 ± 60.15 0.015 Choroidal Layer (μm) Total Choroidal Layer Thickness (TCLT) 358.4 ± 104.5 355.6 ± 61.41 0.911 -Inner Choroidal Layer Thickness (ICLT) 47.76 ± 19.72 45.36 ± 16.59 0.536 -Outer Choroidal Layer Thickness (OCLT) 310.70 ± 98.64 310.30 ± 65.80 0.987 Subretinal Fluid Area (SFA) 145,069 ± 135,059 47,805 ± 92,182 0.0005 Abbrev. LogMAR, logarithm of the minimum angle of resolution; BCVA, best-corrected visual acuity; OCT, optical coherence tomography. Data presented as mean ± SD. Bold indicates statistically significant. [REV. MED. CLIN. CONDES - 2023; 34(3) 187-194]
191 Correlation of structural changes with visual acuity The correlations of structural changes with logMAR BCVA were explored (Table 3). We found a significant positive correlation between logMAR BCVA and retinal nerve fiber layer (RNFL), ONL, TRLT, ORLT, and subretinal fluid area (r=0.419, 0.477, 0.483, 0.540, and 0.683, respectively, table 3) at baseline, while other layers did not show good correlation. At the final visit, no significant correlations were detected (Table 3). We then examined whether there was any correlation between changes in the logMAR BCVA (ΔVA) and structural changes (Δstructural changes) from the baseline to the final visit. Similarly, no correlations were observed (Table 3). A multivariate analysis was further conducted using data at the final visit. The decrease in the PRL was associated with better visual acuity in the univariate analysis. However, this result was not statistically significant in the multivariate analysis (Table 4). DISCUSSION This study showed that structural changes, marked by the reduction of TRLT (especially in the INL and ONL) and subretinal fluid accumulation, were observed in DME patients administered with three doses of IVR at one-month intervals. The efficacy of ranibizumab for DME treatment has been examined to some extent, and although the serum level of VEGF after 4 weeks of IVR did not statistically differ from baseline13, suppression of VEGF level is observed in aqueous humor samples14, reflecting that, locally, VEGF production within the eye is critical in progression and treatment of DME. The anti-VEGF drug ranibizumab also induced retinal reperfusion by inhibiting endothelial cell migration and neovascularization15,16. Additionally, ranibizumab treatments attenuated the vascular leakage in the DL-2-aminoadipic acid (DLAAA)-induced retinal neovascularization model17. Hence, a reduction of subretinal fluid accumulation as well as retinal layer thickness would be expected. On the other hand, the effects of IVR injection on choroid layer thickness (CLT) in DME eyes are often inconsistent18-21. In this case, our results showed that CLT did not change after IVR treatment. Notably, a reduction of CLT is observed in DR treated with laser pan-retinal photocoagulation (PRP)22. Nonetheless, the exact mechanism underlying choroidal layer changes in DME eyes has yet to be elucidated. It has been demonstrated that vascuTable 3. Association between visual acuity and structural changes at each time point Parameters Baseline Final visit LogMAR BCVA/ structural changes Retinal Layer ( μm) Retinal Nerve Fiber Layer (RNFL) r = 0.419; p = 0.032 r = 0.292; p = 0.198 r = –0.004; p = 0.982 Ganglion Cell Layer (GCL) r = 0.306; p = 0.093 r = 0.042; p = 0.837 r = –0.137; p = 0.503 Inner Plexiform Layer (IPL) r = 0.310; p = 0.089 r = 0.303; p = 0.131 r = –0.096; p = 0.639 Inner Nuclear Layer (INL) r = 0.279; p = 0.127 r = 0.037; p = 0.856 r = –0.157; p = 0.443 Outer Plexiform Layer (OPL) r = 0.281; p = 0.125 r = –0.178; p = 0.384 r = 0.054; p = 0.793 Outer Nuclear Layer (ONL) r = 0.477; p = 0.006 r = 0.255; p = 0.102 r = 0.298; p = 0.138 Photoreceptor Layer (PRL) r = 0.069; p = 0.710 r = –0.327; p = 0.102 r = 0.302; p = 0.133 Total Retinal Layer Thickness (TRLT) r = 0.483; p = 0.006 r = 0.019; p = 0.925 r = 0.061; p = 0.771 -Inner Retinal Layer Thickness (IRLT) r = 0.077; p = 0.684 r = –0.084; p = 0.686 r = –0.367; p = 0.071 -Outer Retinal Layer Thickness (ORLT) r = 0.540; p = 0.002 r = –0.207; p = 0.318 r = 0.188; p = 0.366 Choroidal Layer (μm) Total Choroidal Layer Thickness (TCLT) r = 0.0004; p = 0.998 r = 0.192; p = 0.346 r = –0.102; p = 0.617 -Inner Choroidal Layer Thickness (ICLT) r = 0.186; p = 0.315 r = –0.084; p = 0.682 r = 0.026; p = 0.896 -Outer Choroidal Layer Thickness (OCLT) r = –0.037; p = 0.876 r = 0.200; p = 0.325 r = –0.241; p = 0.367 Subretinal Fluid Area (SFA) r = 0.683; p = 0.0001 r = –0.081; p = 0.698 r = 0.094; p = 0.651 [Evaluation of marker-based optic coherence tomography findings in diabetic macular edema treated with intravitreal... - Yuliono Trika Nur Hasan et al.]
192 lar development in the choroidal layer is influenced by VEGF23. Therefore, it seems that CLT may be correlated with the upregulation of VEGF expression and subsequently increased CLT. Nonetheless, a recent study by Wang et al. suggests that choroidal response to ranibizumab treatment depends on DME types24. It is still unclear whether the onset of DME may also influence CLT. It is also possible to speculate that other treatment modalities may have influenced other factors rather than directly regulated VEGF expression. Hence, further related studies are required to explore the possible mechanism. According to ROC analysis, reduction in the subretinal fluid area remained a crucial marker in determining the treatment outcome. Nevertheless, a decrease in the ONL can be considered a plausible alternative in several cases where fluid accumulations Table 4. Multivariate linear regression analysis of factors with influence on LogMAR BCVA after 3 months ranibizumab treatment Univariate analysis Multivariate Analysis (Adjusted R2 = 0.235)* t p-val Unstandardized Regression Coefficient β Unstandardized Regression Coefficient β p-val Constant 1.107 0.000 Retinal Layer ( μm) Retinal Nerve Fiber Layer (RNFL) 1.889 0.076 Ganglion Cell Layer (GCL) –0.965 0.349 Inner Plexiform Layer (IPL) –0.731 0.475 Inner Nuclear Layer (INL) –0.866 0.399 Outer Plexiform Layer (OPL) 0.925 0.369 Outer Nuclear Layer (ONL) –1.805 0.090 Photoreceptor Layer (PRL) –2.556 0.020 –0.007 –0.327 0.103 Total Retinal Layer Thickness (TRLT) –0.375 0.712 -Inner Retinal Layer Thickness (IRLT) –0.503 0.622 -Outer Retinal Layer Thickness (ORLT) –0.109 0.914 Choroidal Layer ( μm) Total Choroidal Layer Thickness (TCLT) –0.695 0.497 -Inner Choroidal Layer Thickness (ICLT) 0.302 0.767 -Outer Choroidal Layer Thickness (OCLT) –0.710 0.488 Subretinal Fluid Area (SFA) 0.348 0.733 Dependent variable: LogMAR best-corrected vision acuity (BCVA) at the final visit. Explanatory variable: retinal and choroidal layer thickness, subretinal fluid area. *Adjusted coefficient of multiple determination. are minimal and hard to assess. Visual acuity gain was best associated with increased PRL, which concords with a previous study indicating photoreceptor thinning in DR/DME patients25. Indeed, the accumulation of fluid in the cystoid space has been proven to stimulate photoreceptor damage in patients with DME26,27. Although PRL degeneration has been previously demonstrated in the early onset of DR4,26, our current findings implied that ranibizumab treatment effectively reduces fluid accumulation and subsequently improves neural recovery in the PRL. Nonetheless, further studies with a larger sample size are needed to confirm this finding. Despite the positive results, several limitations should be noted. Firstly, we found that six patients seemed non-responsive to ranibizumab treatment and required additional injections. Secondly, [REV. MED. CLIN. CONDES - 2023; 34(3) 187-194]
193 patients with better visual acuity at baseline had less room for visual improvement, which may influence the study outcome. Lastly, the retrospective nature and relatively small sample size of this study might have hindered the potential correlations between the variables measured. In conclusion, individual segmentation in the retina, particularly in the PRL, may have a clinical value for monitoring a short-term response of ranibizumab therapy in DME patients. Further prospective and long-term studies with a large sample size are still required. Acknowledgment This study was supported by funding from the Faculty of Medicine and Health Sciences, Maulana Malik State Islamic University with the Ref. No. DIPA-025.04.02.423812/2022. Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. 1. Chen NN, Chen WD, Lai CH, Kuo CN, Chen CL, Huang JC, et al. Optical Coherence Tomographic Patterns as Predictors of Structural Outcome After Intravitreal Ranibizumab in Diabetic Macula Edema. Clin Ophthalmol. 2020;14:4023-4030. doi: 10.2147/ OPTH.S264669 2. Selim KM, Sahan D, Muhittin T, Osman C, Mustafa O. Increased levels of vascular endothelial growth factor in the aqueous humor of patients with diabetic retinopathy. Indian J Ophthalmol. 2010;58(5):375-379. doi: 10.4103/0301-4738.67042 3. Endo M, Yanagisawa K, Tsuchida K, Okamoto T, Matsushita T, Higuchi M, Matsuda A, Takeuchi M, Makita Z, Koike T. Increased levels of vascular endothelial growth factor and advanced glycation end products in aqueous humor of patients with diabetic retinopathy. Horm Metab Res. 2001;33(5):317-322. doi: 10.1055/s-200115122 4. Ulhaq ZS, Hasan YTN, Herawangsa S, Audris MA, Al Farizy MF, Aditya RD, et al. The retinal nerve fiber layer thickness is useful for the assessment of diabetic retinopathy severity. Diabetes Epidemiol Manag. 2022;7:100075. doi: 10.1016/j.deman.2022.100075 5. Starace V, Battista M, Brambati M, Cavalleri M, Bertuzzi F, Amato A, et al. The role of inflammation and neurodegeneration in diabetic macular edema. Ther Adv Ophthalmol. 2021;13:25158414211055963. doi: 10.1177/25158414211055963 6. Ulhaq ZS, Soraya GV, Budu, Wulandari LR. The role of IL-6-174 G/C polymorphism and intraocular IL-6 levels in the pathogenesis of ocular diseases: a systematic review and meta-analysis. Sci Rep. 2020;10(1):17453. doi: 10.1038/s41598-020-74203-9 7. Němčanský J, Stepanov A, Veith M, Koubek M, Kopecký A, Němčanská S, et al. EFFECT OF BASELINE CENTRAL RETINAL THICKNESS ON THE RESULTS OF TREATMENT OF DIABETIC MACULAR EDEMA WITH AFLIBERCEPT: REAL-LIFE EVIDENCE IN THE CZECH REPUBLIC. Cesk Slov Oftalmol. 2022;78(2):64-70. doi: 10.31348/2022/9 8. Xu Y, Qu Y, Suo Y, Gao J, Chen X, Liu K, et al. 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195 INFORMACIÓN DEL ARTÍCULO Historia del Artículo: Recibido: 15 11 2022 Aceptado: 05 05 2023 Key words: Intensive Care Units; COVID-19; Respiratory Distress Syndrome; Prone Position; Respiration, Artificial. Palabras clave: Unidades de Cuidados Intensivos; COVID-19; Síndrome de Dificultad Respiratoria; Posición de Prono; Respiración Artificial. RESUMEN Introducción: Para el manejo del síndrome de distrés respiratorio agudo (SDRA) moderado a severo por COVID-19 se recomendó el uso de ventilación mecánica protectora y decúbito prono debido a la gran utilidad reportada sobre la oxigenación y mortalidad. Nuestro objetivo es describir el comportamiento gasométrico y mecánico en sujetos con SDRA por COVID-19 manejados con ventilación mecánica protectora y decúbito prono en un hospital de alta complejidad. Método: Estudio observacional. Se incluyeron sujetos ≥ 18 años con SDRA por COVID-19. Se inició ventilación mecánica protectora desde la primera conexión a ventilación invasiva, mientras que el decúbito prono inició con PaO2/FIO2 <150. Se realizó un seguimiento durante y posterior al decúbito prono. Se realizó un análisis descriptivo de las características basales y comparación de medias entre grupos mediante prueba de Dunn y Friedman. La significación estadística se estableció en p<0,05 a dos colas en todos los análisis. Resultados: Se estudiaron 74 sujetos, 58% corresponden a hombres con media de 60 años. La oxigenación valorada mediante PaO2 (76 a 98 mmHg, p<0,05) y PaO 2/FIO2 (100 a 161, p<0,05) muestra un incremento significativo durante la primera hora de tratamiento con estabilidad de los valores más allá de las 48 horas posteriores al prono. Los parámetros de mecánica pulmonar se mantienen constantes y dentro de rangos protectores (p=0,18). Conclusión: La estrategia de ventilación mecánica protectora y decúbito prono igual o mayor a 48 horas, en sujetos con SDRA moderado a severo secundario a COVID-19, mejora y mantiene la oxigenación hasta 48 horas después de la supinación. Efectos del decúbito prono en síndrome de distrés respiratorio agudo secundario a COVID-19: experiencia en un hospital de alta complejidad Effects of prone position in acute respiratory distress syndrome secondary to COVID-19: Experience in a high complexity hospital Paulina Vivanco-Aravenaa,b , Iván Hernándeza, Cristián Troncozoc, Francisco Gómeza, Rita Pinod. a Servicio de Kinesiología Intensiva y Soporte Ventilatorio, Hospital de Urgencia y Asistencia Pública. Santiago, Chile. b Laboratorio de Ciencias del Ejercicio y Rehabilitación, Escuela de Kinesiología, Facultd de Ciencias de la Rehabilitación, Universidad Andrés Bello. Santiago, Chile. c Jefe de Servicio de Kinesiología Intensiva y Soporte Ventilatorio, Hospital de Urgencia y Asistencia Pública. Santiago, Chile. d Kinesiología, Clínica INDISA. Santiago, Chile. Autor para correspondencia Correo electrónico: pfvivanco@uc.cl https://doi.org/10.1016/j.rmclc.2023.05.001 e-ISSN: 2531-0186/ ISSN: 0716-8640/© 2023 Revista Médica Clínica Las Condes. Este es un artículo Open Access bajo la licencia CC BY-NC-ND (http://creativecommons.org/licenses/by-nc-nd/4.0/). [REV. MED. CLIN. CONDES - 2023; 34(3) 195-203] REVISTA MÉDICA CLÍNICA LAS CONDES https://www.journals.elsevier.com/revista-medica-clinica-las-condes ORIGINAL
196 [REV. MED. CLIN. CONDES - 2023; 34(3) 195-203] ABSTRACT Introduction: The use of protective mechanical ventilation and prone position was recommended for the management of moderate to severe acute respiratory distress syndrome (ARDS) due to COVID-19, as a result of its reported utility on oxygenation and mortality. Our objective is to describe gasometric and mechanical behavior in subjects with ARDS due to COVID-19 managed with protective mechanical ventilation and prone position in a high complexity hospital. Method: Observational study. Subjects ≥18 years of age with ARDS due to COVID-19 were included. Protective mechanical ventilation was started from the first connection to invasive ventilation, while the prone position started with PaO2/FIO2 <150. Follow-up was performed during and after the prone position. A descriptive analysis of baseline characteristics and comparison of means between groups was performed using the Dunn and Friedman test. Statistical significance corresponds to p<0.05 in all analyses. Results: 74 subjects were studied, 58% correspond to men with a mean age of 60 years. There is evidence of a significant increase in arterial oxygenation assessed by PaO2 (76 to 98 mmHg, p<0.05) and PaO 2/FIO2 (100 to 161, p<0.05) during the first hour of treatment, with stability of values beyond 48 hours after supination. Pulmonary mechanics values remain constant within the established protection range (p=0,18). Conclusion: The strategy of protective mechanical ventilation and prone position for 48 or more hours, in subjects with moderate to severe ARDS due to COVID-19, improves and maintains arterial oxygenation up to 48 hours after supination. INTRODUCCIÓN La pandemia de COVID-19 ha llevado a un aumento sustancial en el número de pacientes ingresados en el hospital con insuficiencia respiratoria1. La mayoría de estos pacientes requieren soporte ventilatorio no invasivo, sin embargo, el empeoramiento de la condición es extremadamente alto, siendo necesaria la intubación y conexión a ventilación mecánica invasiva (VMI), saturando los recursos hospitalarios y disponibilidad de las camas de las unidades de cuidados intensivos2,3. El síndrome de distrés respiratorio agudo (SDRA) es una causa común de insuficiencia respiratoria en pacientes gravemente enfermos. Es definida por la aparición aguda de hipoxemia, edema pulmonar no cardiogénico, reducción de la compliance pulmonar, aumento del trabajo ventilatorio y la necesidad de presión positiva mediante ventilación mecánica4,5. La prevalencia de este síndrome corresponde a un 23% en pacientes con ventilación mecánica, mientras que la mortalidad hospitalaria fue entre un 40 y 46% en los SDRA moderado y grave, respectivamente6. Para el tratamiento del SDRA, aún no se ha demostrado que los tratamientos farmacológicos dirigidos a la patología subyacente sean efectivos, hasta ahora el manejo sigue siendo el apoyo con ventilación mecánica protectora7. La ventilación mecánica protectora implica el uso limitado de los volúmenes corrientes (6 a 8 ml por kilogramo de peso ideal); una presión meseta o plateau menor a 30 cmH20 y una presión de distensión o driving pressure inferior a 15 cmH203,8,9. El uso de esta estrategia ventilatoria ha demostrado reducir la mortalidad en un 8% (Acute Respiratory Distress Syndrome, ARDS Network; 31% vs. 39,8%; p=0,007)10,11. Otra intervención complementaria que ha demostrado un efecto positivo en el manejo del SDRA es la maniobra de decúbito prono, la cual mejora la oxigenación debido a una optimización de la relación ventilación-perfusión donde las áreas dorsales, que anatómicamente cuentan con mayor número de unidades alveolares, ya no están comprimidas por el peso de la cavidad abdominal y mediastino, favoreciendo la reapertura y reclutamiento de las regiones más eficientes en el intercambio de gases9,10,12. Por otra parte, la posición decúbito prono ha mostrado una reducción en la mortalidad relacionada con la disminución de la sobredistensión y el reclutamiento/desreclutamiento alveolar cíclico, con la consecuente reducción del riesgo de lesión pulmonar asociada a la ventilación mecánica13-15. Por lo tanto, el uso de ventilación mecánica protectora y decúbito prono en SDRA secundario a COVID-19 podría reducir la mortalidad y el daño asociado a la VMI. Según estos antecedentes, nuestro objetivo es describir el comportamiento gasométrico y mecánico en sujetos son SDRA por COVID-19 tratados con ventilación mecánica protectora y decúbito prono en Hospital de Urgencia Asistencia Pública (HUAP). MATERIAL Y MÉTODO Diseño del estudio: Estudio observacional, retrospectivo, realizado entre mayo y julio del 2020. Participantes: Se incluyen a todos los sujetos ingresados a la Unidad de Cuidados Intensivos (UCI), mayores o iguales a 18 años con diagnóstico de SDRA moderado a severo secundario a COVID-19 según los criterios de Berlín. Es decir, aparición temprana con duración menor a 1 semana de evolución, opacidades radiológicas bi-
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