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Ítem Health screening of middle-aged women: what factors impact longevity?(The North American Menopause Society, 2022-08) Blumel, Juan E.; Aedo, Sócrates; Murray, Nigel P.; Vallejo, María S.Objective The aim of this study was to measure the impact of different risk factors in middle-aged women on longevity evaluated after three decades of an initial health screening. Methods Women who received an annual check-up between 1990 and 1993 were recruited. Anamnesis and physical examination were recorded. Blood samples for the measurement of glycemia and lipids were taken. Data are reported as of December 2021. Results A total of 1,158 women aged 40 to 60 were studied. At 30.9 years of follow-up, the Kaplan-Meier overall survival was 75.6% (95% confidence interval, 72.6-78.3). The main causes of the 260 deaths observed were the following: cancer (n = 88; 33.8%), cardiovascular disease (n = 55; 21.2%), and infectious disease (n = 41; 15.8%). The following hazard ratios were found with the flexible parametric survival model: personal history of fracture (hazard ratio, 2.55; 95% confidence interval, 1.29-5.02; P = 0.007), type 2 diabetes mellitus (2.14; 1.18-3.88; P = 0.012), personal history of heart disease (1.85; 1.09-3.13; P = 0.022), chronic arterial hypertension (1.65; 1.25-2.17; P < 0.001), postmenopausal status (1.60; 1.13-2.26; P = 0.008), unskilled jobs (1.56; 1.17-2.07; P = 0.002), cigarette smoking (1.51; 1.17-1.94; P = 0.002), age (1.06; 1.03-1.09; P < 0.001), body mass index (1.04; 1.01-1.07; P = 0.004), multiparous (0.72; 0.56-0.93; P = 0.012), and active sexual intercourse (0.68; 0.52-0.87; P = 0.003). Lipid disorders did not reach statistical significance as a risk factor. Conclusions In this cohort, it was observed that most of the classic risk factors for mortality were present. However, a history of fracture appears in middle-aged women as a strong predictor of mortality, surpassing diabetes and arterial hypertension. Multiparity, on the other hand, was a protective factor.Ítem Physiological and clinical effects of trunk inclination adjustment in patients with respiratory failure: a scoping review and narrative synthesis(BMC, 2024-07-09) Benites, Martín Hernán; Zapata‑Canivilo, Marcelo; Poblete, Fabian; Labbe, Francisco; Battiato, Romina; Ferre, Andrés; Dreyse, Jorge; Bugedo, Guillermo; Bruhn, Alejandro; Costa, Eduardo L. V.; Retamal, JaimeBackground Adjusting trunk inclination from a semirecumbent position to a supinefat position or vice versa in patients with respiratory failure signifcantly afects numerous aspects of respiratory physiology including respiratory mechanics, oxygenation, endexpiratory lung volume, and ventilatory efciency. Despite these observed efects, the current clinical evidence regarding this positioning manoeuvre is limited. This study undertakes a scoping review of patients with respiratory failure undergoing mechanical ventilation to assess the efect of trunk inclination on physiological lung parameters. Methods The PubMed, Cochrane, and Scopus databases were systematically searched from 2003 to 2023. Interventions: Changes in trunk inclination. Measurements: Four domains were evaluated in this study: 1) respiratory mechanics, 2) ventilation distribution, 3) oxygenation, and 4) ventilatory efciency. Results After searching the three databases and removing duplicates, 220 studies were screened. Of these, 37 were assessed in detail, and 13 were included in the fnal analysis, comprising 274 patients. All selected studies were experimental, and assessed respiratory mechanics, ventilation distribution, oxygenation, and ventilatory efciency, primarily within 60 min post postural change. Conclusion In patients with acute respiratory failure, transitioning from a supine to a semirecumbent position leads to decreased respiratory system compliance and increased airway driving pressure. Additionally, CARDS patients experienced an improvement in ventilatory efciency, which resulted in lower PaCO2 levels. Improvements in oxygenation were observed in a few patients and only in those who exhibited an increase in EELV upon moving to a semi recumbent position. Therefore, the trunk inclination angle must be accurately reported in patients with respiratory failure under mechanical ventilationÍtem Systematic review and meta-analysis of right subclavian artery variants and their correlation with cervical-thoracic clinical conditions(Wolkers Kluwer Health, 2024-12-13) Valenzuela Fuenzalida, Juan José; Orellana-Donoso, Mathias; Perez-Jiménez, Daniela; Farfán Cabello, Emilo; Gold Semmler, Marjorie; Becerra Farfan, Álvaro; Román, Camila; Nova Baeza, PabloBackground: A high incidence of anatomical variations in the origin of the branches of the aortic arch has been reported, Nowadays, this variation is considered the most frequent in the aortic arch, its prevalence being estimated between 0.5% and 2.5% of the population. To understand its origin, knowledge of embryonic development is necessary. Methods: We searched the MEDLINE, Scopus, Web of Science, Google Scholar, Cumulative Index to Nursing and Allied Health Literature, and Latin-American literature and caribean of health sciences databases with dates ranging from their inception to June 2023. Study selection, data extraction, and methodological quality were assessed with the guaranteed tool for anatomical studies (Anatomical Quality Assurance). Finally, the pooled prevalence was estimated using a random effects model. Results: Thirty-nine studies were found that met the eligibility criteria. Twenty studies with a total of 41,178 subjects were included in the analysis. The overall prevalence of an ARSA variant was 1% (95% confidence interval = 1%–2%), the clinical findings found are that if ARSA is symptomatic it could produce changes in the hemodynamic function of the thoracocervical region in addition to other associated symptomatic complications in surrounding structures. Conclusions: ARSA can cause several types of alterations in the cervical or thoracic region, resulting in various clinical complications, such as lusory dysphagia. Hence, knowing this variant is extremely important for surgeons, especially those who treat the cervico-thoracic region. The low prevalence of ARSA means that many professionals are completely unaware of its existence and possible course and origin. Therefore, this study provides detailed knowledge of ARSA so that professionals can make better diagnoses and treatment of ARSA.Ítem Neuronas espejo y sistemas neuronales asociados al aprendizaje clínico: una revisión de la literatura(Federación Latinoamericana de Simulación Clínica y Seguridad del Paciente, 2023) Orquera, Paulo; Valenzuela, Juan José; Orellana-Donoso, Mathias; Gold, Marjorie; Abascal, NancyIntroducción: se ha sugerido que las neuronas espejo (MN, por sus siglas en inglés) desempeñan un papel fundamental en los procesos sociales de orden superior, incluido el aprendizaje motor, la comprensión de la acción, el aprendizaje por imitación, la toma de perspectiva, la comprensión de las emociones faciales y la empatía. Sin embargo, aún no existen estudios que evalúen y demuestren un papel importante de las MN en el aprendizaje por imitación en instancias como la simulación clínica para estudiantes universitarios de carreras de ciencias de la salud. Objetivo: describir cómo algunos mecanismos neuronales pueden contribuir al aprendizaje basado en la imitación y discutir su papel en la simulación clínica. Material y métodos: se realizó una búsqueda sistemática en bases de datos electrónicas, con el fin de recopilar la literatura disponible sobre el tema. Resultados: se incluyeron 22 artículos después de aplicar los criterios de inclusión y exclusión. Siete de ellos abordaron el proceso de aprendizaje a través de neuronas espejo, siete lo hicieron a través de la imitación y dos más trataron el aprendizaje sensoriomotor a través de MN. Conclusiones: aunque parece que el sistema de las MN tiene implicaciones que podrían subyacer al aprendizaje basado en simulación clínica, se necesitan más estudios primarios con alto rigor metodológico y experimentos para medir la actividad del sistema de las MN en el aprendizaje basado en simulación clínica y su papel para establecer conclusiones más concretas.Ítem Pannexin-1 expression in tumor cells correlates with colon cancer progression and survival(Elsevier, 2024) Fierro Arenas, Aaron; Landskron, Glauben; Camhi-Vainroj, Ilan; Basterrechea, Benjamin; Parada Venegas, Daniela; Lobos Gonzalez, Lorena; Dubois Camacho, Karen; Araneda, Catalina; Romero, Camila; Dominguez, Antonia; Vasquez, Gonzalo; Lopez K, Francisco; Alvarez, Karin; Gonzalez, Carlos M; Hager Ribeiro, Carolina; Balboa, Elisa; Eugenin, Eliseo; Hermoso, Marcela A; De la Fuente, MarjorieAims: Pannexin-1 (PANX1) is a hemichannel that releases ATP upon opening, initiating inflammation, cell proliferation, and migration. However, the role of PANX1 channels in colon cancer remains poorly understood, thus constituting the focus of this study. Main methods: PANX1 mRNA expression was analyzed using multiple cancer databases. PANX1 protein expression and distribution were evaluated by immunohistochemistry on primary tumor tissue and non-tumor colonic mucosa from colon cancer patients. PANX1 inhibitors (probenecid or 10Panx) were used to assess colon cancer cell lines viability. To study the role of PANX1 in vivo, a subcutaneous xenograft model using HCT116 cells was performed in BALB/c NOD/SCID immunodeficient mice to evaluate tumor growth under PANX1 inhibition using probenecid. Key findings: PANX1 mRNA was upregulated in colon cancer tissue compared to non-tumor colonic mucosa. Elevated PANX1 mRNA expression in tumors correlated with worse disease-free survival. PANX1 protein abundance was increased on tumor cells compared to epithelial cells in paired samples, in a cancer stagedependent manner. In vitro and in vivo experiments indicated that blocking PANX1 reduced cell viability and tumor growth. Significance: PANX1 can be used as a biomarker of colon cancer progression and blocking PANX1 channel opening could be used as a potential therapeutic strategy against this disease.Ítem Exploring the lutein therapeutic potential in steatotic liver disease: mechanistic insights and future directions(Frontiers Media S.A., 2024) Balboa, Elisa; Saud, Faride; Parra Ruiz, Claudia; De la Fuente, Marjorie; Landskron, Glauben; Zanlungo, SilvanaThe global prevalence of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is increasing, now affecting 25%–30% of the population worldwide. MASLD, characterized by hepatic steatosis, results from an imbalance in lipid metabolism, leading to oxidative stress, lipoperoxidation, and inflammation. The activation of autophagy, particularly lipophagy, alleviates hepatic steatosis by regulating intracellular lipid levels. Lutein, a carotenoid with antioxidant and anti-inflammatory properties, protects against liver damage, and individuals who consume high amounts of lutein have a lower risk of developing MASLD. Evidence suggests that lutein could modulate autophagy-related signaling pathways, such as the transcription factor EB (TFEB). TFEB plays a crucial role in regulating lipid homeostasis by linking autophagy to energy metabolism at the transcriptional level, making TFEB a potential target against MASLD. STARD3, a transmembrane protein that binds and transports cholesterol and sphingosine from lysosomes to the endoplasmic reticulum and mitochondria, has been shown to transport and bind lutein with high affinity. This protein may play a crucial role in the uptake and transport of lutein in the liver, contributing to the decrease in hepatic steatosis and the regulation of oxidative stress and inflammation. This review summarizes current knowledge on the role of lutein in lipophagy, the pathways it is involved in, its relationship with STARD3, and its potential as a pharmacological strategy to treat hepatic steatosis.Ítem Tratamiento de sobrecrecimiento bacteriano en el intestino delgado en pacientes chilenos con síndrome de intestino irritable: un estudio prospectivo y comparativo(Elsevier, 2024-11-12) von Muhlenbrock, Christian; Landskron, Glauben; Madrid-Silva, Ana MariaIntroducción y objetivos: Los pacientes con trastornos del eje intestino-cerebro, como el síndrome de intestino irritable (SII), a menudo muestran sobrecrecimiento bacteriano en el intestino delgado (SBID). Su tratamiento incluye rifaximina RF), ciprofloxacino (CF), neomicina, sulfametoxazol-trimetoprima y metronidazol (MZ). La RF es un antibiótico no absorbible, que se ha observado que tiene pocos efectos secundarios. Nuestro objetivo fue evaluar la respuesta sintomática y la erradicación del SBID en pacientes con SII, utilizando 3 regímenes antibióticos. Métodos: Se realizó un estudio doble ciego, aleatorizado y prospectivo con pacientes con SII mayores de 18 años, utilizando el cuestionario de Roma IV y la prueba de aliento con lactulosa. Los pacientes diagnosticados con SBID fueron asignados aleatoriamente para recibir tratamiento con antibiótico. El grupo A recibió tratamiento con RF, el grupo B con CF y el grupo C con MZ, cada uno durante 10 días. La respuesta al tratamiento fue evaluada en función de la tasa de erradicación del SBID 15 días después de completar la terapia, utilizando pruebas de aliento con hidrógeno y metano con lactulosa. Los síntomas autorreportados fueron registrados en una escala de Likert de 10 puntos, antes, durante y después del tratamiento. Resultados: Se incluyó a 97 pacientes con SII y SBID, de los cuales el 81% completó el tratamiento. El 59% de los pacientes tratados con RF logró la erradicación del SBID, frente al 53% y 79% de los pacientes tratados con CR y MZ, respectivamente. En el grupo de metronidazol los niveles de metano disminuyeron más que en los otros 2 grupos. Sin embargo, la mayor disminución en dolor abdominal e inflamación fue observada en el grupo de RF, con un menor porcentaje de eventos adversos. Conclusiones: Los pacientes con SII y SBID se benefician de la terapia con antibióticos. El MZ mostró la mejor tasa de erradicación de SBID, pero la RF mostró una mejoría sintomática más importante y una menor tasa de eventos adversos.Ítem Clinical course of atypical parathyroid neoplasm with soft tissue extension(Wiley, 2024-08-19) Feldman, Hope; Busaidy, Naifa; Tame-Elorduy, Andres; Silva-Figueroa, Angélica; Halfteck, Gili; Merriman, Kelly; Waguespack, Steven; Graham, Paul; Williams, Michelle; Perrier, NancyBackground and Objectives: The American Joint Committee on Cancer (AJCC) TNM staging system defines atypical parathyroid neoplasia (APN) as tumor in situ (Tis) and reserves the definition of parathyroid carcinoma (PC) to parathyroid tumor with invasion into surrounding structures. Because the parathyroid gland has no true capsule, “extension” with APN versus microscopic “invasion” of surrounding soft tissue can be difficult and confusing for clinicians. We aimed to determine the clinical course of atypical parathyroid neoplasm with and without soft tissue extension and parathyroid carcinoma with only soft tissue invasion (pT1) and to report the outcomes. Methods: Following an IRB‐approved protocol, we identified all patients treated for parathyroid neoplasm or cancer at our single tertiary care cancer center from 1990 to 2021. We excluded all patients with evidence of clinical or pathologic gross invasion into surrounding structures (pT2 or higher), lymph node involvement, or metastatic disease. By definition, this excluded all cases where the distinction was clinically evident to the surgeon at the time of the operation based on finding a hard, firm, sticky, or discolored parathyroid gland. Only patients with pathologic T1 (pT1) parathyroid carcinoma or APN were included. All pathologic examinations were independently re‐reviewed by a single designated expert senior endocrine pathologist. The definition of APN strictly followed the WHO definition of a clinically worrisome lesion having features including fibrous bands or increased mitotic rate, necrosis, or trabecular growth that did not meet robust criteria for frank invasion. Pathologic T1 disease was defined as invasion limited to soft tissue. Analyses were performed using R version 4.0.2 and Jamovi. Results: Of all PC patients at our institution, only 71 met the strict inclusion criteria of APN or pT1. Forty‐four patients had pT1 disease and 27 had APN: 12 of the APN had soft tissue extension, and 15 had no soft tissue extension. The groups were similar with regard to age at diagnosis (p = 0.328). The average follow‐up duration was 84 months from initial surgical intervention. Of the 12 with APN, one patient (1/12; 8%) with soft tissue extension recurred, developed distant metastases, andsubsequently died during follow up. Of the 44 patients with pT1 PC, six developed distant metastases and 13 (13/44; 30%) died during the follow‐up period. One patient with APN and soft tissue extension recurred and died and no patient with APN and no soft tissue extension died. Conclusions: Patients with APN and extension into soft tissue have a clinical course similar to that of APN without soft tissue extension. APN with soft tissue extension is a different disease from pT1 disease with invasion of soft tissue. The pTis classification appears justified for APN with and without soft tissue extension.Ítem Antidiabetic potential of extracts from Cylindropuntia imbricata (Haw.) F.M. Knuth, Opuntia engelmannii Salm-Dyck ex Engelm., Ibervillea sonorae (S. Wats.) Greene and Theobroma cacao L.(Universidad Nacional Autónoma de México; Facultad de Estudios Superiores Zaragoza., 2024-07-30) De la Sota- Esparza, Gastaldo Emmanuel; Alvarado-Vásquez, Marco Antonio; Rivas-Morales, Catalina; Rocha-Estrada, Alejandra; Chavez-Reyes, Arturo; Ortíz-Martínez, David MizaelDiabetes mellitus is a disease that affects more than 537 million people in the world without decreasing. When diabetes becomes complicated, it damages several organs until it causes death. The drugs in use to counteract the disease produce side effects; a circumstance that has led to research on plants with anti-diabetic properties. The objective of this study was to evaluate the antidiabetic potential of extracts obtained by maceration of the following parts of the plant: Cylindropuntia imbricata (Cactaceae) cladode and seed, Opuntia engelmannii (Cactaceae) cladode and seed, Ibervillea sonorae (Cucurbitaceae) root and Theobroma cacao (Malvaceae) seed mixed with solvents of different polarity (hexane, ethyl acetate, dichloromethane and methanol). A total of 24 extracts were obtained and subjected to the following analyses: 1) phytochemical screening to determine their composition, 2) toxicity in B16F10 cells using the alamar blue test, 3) antioxidant capacity through DPPH inhibition, and 4) in vitro evaluation to determine their antihyperglycemic capacity (inhibition of alpha-glucosidase). The results obtained from methanolic extracts with O. engelmannii and T. cacao seeds, as well as ethyl acetate extracts with T. cacao and C. imbricata seeds showed antioxidant and antihyperglycemic activity. No toxicity in B16F10 cells, and antidiabetic potential in vitro. La diabetes mellitus es una enfermedad que no decrece y afecta a más de 537 millones de personas en el mundo. La diabetes al complicarse daña varios órganos hasta causar la muerte. Los fármacos en uso para contrarrestar la enfermedad producen efectos secundarios; circunstancia que ha propiciado la investigación en plantas con propiedades antidiabéticas. El objetivo de este estudio fue evaluar el potencial antidiabético de los extractos obtenidos por maceración de las siguientes partes de la planta: del cladodio y semilla de Cylindropuntia imbricata (Cactaceae), del cladodio y semilla de Opuntia engelmannii (Cactaceae), de la raíz de Ibervillea sonorae (Cucurbitaceae) y de la semilla de Theobroma cacao (Malvaceae) mezcladas con solventes de diferente polaridad (hexano, acetato de etilo, diclorometano y metanol). Se obtuvieron un total de 24 extractos sometidos a los análisis: 1) de cribado fitoquímico para determinar su composición, 2) de toxicidad en células B16F10 mediante la prueba de azul alamar, 3) de capacidad antioxidante a través de la inhibición de DPPH, y 4) de evaluación in vitro para conocer su capacidad antihiperglucémica (inhibición de la alfa glucosidasa). Los resultados obtenidos, de los extractos metanólicos con las semillas de O. engelmannii y T. cacao, así como los de acetato de etilo con las semillas de T. cacao y C. imbricata mostraron una actividad antioxidante y antihiperglucémica. Sin toxicidad en las células B16F10, y con potencial antidiabético in vitro.Ítem Therapeutic antisense oligonucleotides in oncology: from bench to bedside(MDPI, 2024-08-23) Cakan, Elif; Lara, Olivia D.; Szymanowska, Anna; Bayraktar, Emine; Chavez-Reyes, Arturo; Lopez-Berestein, Gabriel; Amero, Paola; Rodriguez-Aguayo, CristianAdvancements in our comprehension of tumor biology and chemoresistance have spurred the development of treatments that precisely target specific molecules within the body. Despite the expanding landscape of therapeutic options, there persists a demand for innovative approaches to address unmet clinical needs. RNA therapeutics have emerged as a promising frontier in this realm, offering novel avenues for intervention such as RNA interference and the utilization of antisense oligonucleotides (ASOs). ASOs represent a versatile class of therapeutics capable of selectively targeting messenger RNAs (mRNAs) and silencing disease-associated proteins, thereby disrupting pathogenic processes at the molecular level. Recent advancements in chemical modification and carrier molecule design have significantly enhanced the stability, biodistribution, and intracellular uptake of ASOs, thereby bolstering their therapeutic potential. While ASO therapy holds promise across various disease domains, including oncology, coronary angioplasty, neurological disorders, viral, and parasitic diseases, our review manuscript focuses specifically on the application of ASOs in targeted cancer therapies. Through a comprehensive examination of the latest research findings and clinical developments, we delve into the intricacies of ASO-based approaches to cancer treatment, shedding light on their mechanisms of action, therapeutic efficacy, and prospects.Ítem Respiratory system compliance accurately assesses the “Baby Lung” in Pediatric Acute Respiratory Distress Syndrome(The American Thoracis Society, 2024-04-01) Cruces, Pablo; Reveco, Sonia; Caviedes, Paola; Díaz, FrancoThe concept of the “baby lung” has gained widespread recognition in acute respiratory distress syndrome (ARDS) and has significantly influenced the principles of protective mechanical ventilation (MV) (1). This concept is rooted in tomographic studies performed in adult patients with ARDS, which revealed the presence of a smaller, normally aerated lung compartment at the end of expiration and normal specific lung elastance. There is a strong correlation between end-expiratory lung volume (EELV) and respiratory system.Ítem Noninvasive continuous positive airway pressure is a lung- and diaphragm-protective approach in self-inflicted lung injury(The American Thoracis Society, 2024-04-15) Cruces, Pablo; Erranz, Benjamín; Pérez, Agustín; Reveco, Sonia; González, Carlos; Retamal, Jaime; Poblete, Daniela; Hurtado, Daniel E.; Díaz, FrancoStrenuous spontaneous effort can promote lung and diaphragmatic injury in acute lung injury (ALI), phenomena known as “patient self-inflicted lung injury” (P-SILI) and load-induced diaphragmatic injury, respectively (1–3). Although continuous positive airway pressure (CPAP) can relieve hypoxemia and work of breathing (4), it is controversial if it prevents lung and diaphragmatic injury (5, 6). We aimed to investigate the effects of noninvasive CPAP on lung and diaphragmatic injury in an ALI model compared with unassisted animals.Ítem Letter: Development of a Randomized Trial Comparing ICP-Monitor-Based Management of Severe Pediatric Traumatic Brain Injury to Management Based on Imaging and Clinical Examination Without ICP Monitoring-Study Protocol(Wolters Kluwer Health, Inc., 2024) Nielsen, Katie; Caporal, Paula; Díaz, Franco; González-Dambrauskas, Sebastián; Vásquez-Hoyos, Pablo; Domínguez-Rojas, JesúsPediatric traumatic brain injury is a major public health concern, particularly in resource-limited settings where this entity has higher incidence and mortality than developed nations. Despite the disproportionate burden of pediatric traumatic brain injury in low- and middle-income countries (LMICs), the current Brain Trauma Foundation guidelines are largely based on low-quality evidence generated in high-income countries (HICs).1 Adherence to guidelines is challenging in LMICs because of economic constraints, equipment availability, and human resources,2 which may explain disparities in outcomes. We applaud Chesnut et al3 for publishing a randomized controlled trial (RCT) protocol to test the hypothesis of whether intracranial pressure (ICP) monitoring improves outcomes in pediatric severe TBI (psTBI). The RCT will compare outcomes for children receiving ICP-based vs clinical examination and imaging-based management. Their main objective is to generate class I evidence regarding the impact of ICP-driven management in psTBI on long-term outcomes.Ítem Ventilatory load reduction by combined mild hypothermia and ultraprotective mechanical ventilation strategy in severe COVID-19-related acute respiratory distress syndrome: A physiological study.(The Emergency Medicine Association of Turkey, 2024-04) Cruces, Pablo; Moreno, Diego; Reveco, Sonia; Ramírez, Yenny; Díaz, FrancoWe report the feasibility of a combined approach of very low low tidal volume (VT) and mild therapeutic hypothermia (MTH) to decrease the ventilatory load in a severe COVID-19-related acute respiratory distress syndrome (ARDS) cohort. Inclusion criteria was patients ≥18 years old, severe COVID 19 related ARDS, driving pressure ∆P >15 cmH2 O despite low-VT strategy, and extracorporea therapies not available. MTH was induced with a surface cooling device aiming at 34°C. MTH was maintained for 72 h, followed by rewarming of 1°C per day. Data were shown in median (interquartile range, 25%–75%). Mixed effects analysis and Dunnett’s test were used for comparisons. Seven patients were reported. Ventilatory load decreased during the first 24 h, minute ventilation (VE) decreased from 173 (170–192) to 152 (137–170) mL/kg/min (P = 0.007), and mechanical power (MP) decreased from 37 (31–40) to 29 (26–34) J/min (P = 0.03). At the end of the MTH period, the VT, P, and plateau pressure remained consistently close to 3.9 mL/kg predicted body weight, 12 and 26 cmH2 O, respectively. A combined strategy of MTH and ultraprotective mechanical ventilation (MV) decreased VE and MP in severe COVID-19-related ARDS. The decreasing of ventilatory load may allow maintaining MV within safety thresholds.Ítem Prevalence of bacterial codetection and outcomes for infants intubated for respiratory infections(Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies, 2024-07-01) Karsies, Todd; Shein, Steven L.; Díaz, Franco; Vasquez-Hoyos, Pablo; Alexander, Robin; Pon, Steven; González-Dambrauskas, SebastiánOBJECTIVES: To determine the prevalence of respiratory bacterial codetection in children younger than 2 years intubated for acute lower respiratory tract infection (LRTI), primarily viral bronchiolitis, and identify the association of codetection with mechanical ventilation duration. MEASUREMENTS AND MAIN RESULTS: Of the 472 analyzed patients (median age 4.5 mo), 55% had a positive respiratory culture and 29% (n = 138) had codetection. 90% received early antibiotics starting at a median of 0.36 hours after respiratory culture. Median (interquartile range) IMV duration was 151 hours (88, 226), and there were 28 deaths (5.3%). Codetection was more common with younger age, a positive respiratory syncytial virus test, and an admission diagnosis of bronchiolitis; it was less common with an admission diagnosis of pneumonia, with admission to a low-/middle-income site, and in those receiving vasopressors. When adjusted for confounders, codetection was not associated with longer IMV duration (adjusted relative risk 0.854 [95% CI 0.684–1.065]). We could not exclude the possibility that codetection might be associated with a 30-hour shorter IMV duration compared with no codetection, although the CI includes the null value. CONCLUSIONS: Bacterial codetection was present in almost a third of children younger than 2 years requiring intubation and ICU admission for LRTI, but this was not associated with prolonged IMV. Further large studies are needed to evaluate if codetection is associated with shorter IMV duration.Ítem Noninvasive ventilation for Pediatric Acute Respiratory Distress Syndrome: experience from the 2016/2017 Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Prospective Cohort Study(The Society of Critical Care Medicine; The World Federation of Pediatric Intensive and Critical Care Societies, 2023) Díaz, Franco; Emeriaud, Guillaume; Pons-Òdena, Marti; Bhalla, Anoopindar K.; Shein, Steven L.; Killien, Elizabeth Y.; Modesto i Alapont, Vicent; Rowan, Courtney; Baudin, Florent; Lin, John C.; Grégoire, Gabrielle; Napolitano, Natalie; Mayordomo-Colunga, Juan; Cruces, Pablo; Medina, Alberto; Smith, Lincoln; Khemani, Robinder G.Objectives: The worldwide practice and impact of noninvasive ventilation (NIV) in pediatric acute respiratory distress syndrome (PARDS) is unknown. We sought to describe NIV use and associated clinical outcomes in PARDS. Design: Planned ancillary study to the 2016/2017 prospective Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology study. Setting: One hundred five international PICUs. Patients: Patients with newly diagnosed PARDS admitted during 10 study weeks. Interventions: None. Measurements and main results: Children were categorized by their respiratory support at PARDS diagnosis into NIV or invasive mechanical ventilation (IMV) groups. Of 708 subjects with PARDS, 160 patients (23%) received NIV at PARDS diagnosis (NIV group). NIV failure rate (defined as tracheal intubation or death) was 84 of 160 patients (53%). Higher nonrespiratory pediatric logistic organ dysfunction (PELOD-2) score, Pa o2 /F io2 was less than 100 at PARDS diagnosis, immunosuppression, and male sex were independently associated with NIV failure. NIV failure was 100% among patients with nonrespiratory PELOD-2 score greater than 2, Pa o2 /F io2 less than 100, and immunosuppression all present. Among patients with Pa o2 /F io2 greater than 100, children in the NIV group had shorter total duration of NIV and IMV, than the IMV at initial diagnosis group. We failed to identify associations between NIV use and PICU survival in a multivariable Cox regression analysis (hazard ratio 1.04 [95% CI, 0.61-1.80]) or mortality in a propensity score matched analysis ( p = 0.369). Conclusions: Use of NIV at PARDS diagnosis was associated with shorter exposure to IMV in children with mild to moderate hypoxemia. Even though risk of NIV failure was high in some children, we failed to identify greater hazard of mortality in these patientsÍtem Morphological differences between patient self-inflicted and ventilator-induced lung injury: an experimental study(American Thoracic Society, 2023-03) Díaz, FrancoThe role of supraphysiological airway pressure and VT in lung damage during mechanical ventilation (MV) has been studied in-depth, the phenomenon called ventilator-induced lung injury (VILI). Following the same principles, strenuous pontaneous breathing can also be harmful, and the concept of patient self-inflicted lung injury (P-SILI) is proposed (1). However, establishing P-SILI as a pathological entity in acute patients is challenging. There are few P-SILI models focusing on the respiratory effort during MV, showing histological damage in animals with intense respiratory effort (2–4). On the contrary, data regarding strong unassisted spontaneous breathing without MV is lacking. Therefore, we aimed to compare the histopathological findings in animals with acute lung injury (ALI) treated without ventilatory support, injurious MV, and protective MV.Ítem Capnometry after an inspiratory breath hold, PLATCO2, as a surrogate for PaCO2 in mild to moderate Pediatric Acute Respiratory Distress Syndrome: A feasibility study(Wiley Periodicals, 2023-07-10) Cruces, Pablo; Moreno, Diego; Reveco, Sonia; Améstica, Marjorie; Araneda, Patricio; Ramirez, Yennys; Vásquez-Hoyos, Pablo; Díaz, FrancoObjective: Accurate and reliable noninvasive methods to estimate gas exchange are necessary to guide clinical decisions to avoid frequent blood samples in children with pediatric acute respiratory distress syndrome (PARDS). We aimed to investigate the correlation and agreement between end‐tidal PCO2 measured immediately after a 3‐s inspiratory‐hold (PLATCO2) by capnometry and PaCO2 measured by arterial blood gases (ABG) in PARDS. Measurements and Main Results: All patients were in volume‐controlled ventilation mode. The regular end‐tidal P P CO ETCO ( ) 2 2 (without the inspiratory hold) was registered immediately after the ABG sample. An inspiratory‐hold of 3 s was performed for lung mechanics measurements, recording PETCO2 in the breath following the inspiratory‐hold. (PLATCO2). End‐tidal alveolar dead space fraction (AVDSf) was calculated as [( – )/ PP P aCO ETCO aCO ] 2 2 2 and its surrogate (S)AVDSf as [( CO – )/ CO PLAT 2 ETCO PLAT 2 P ] 2 . Measurements of PaCO2 were considered the gold standard. We performed concordance correlation coefficient (ρc), Spearman's correlation (rho), and Bland–Altmann's analysis (mean difference ± SD [limits of agreement, LoA]). Eleven patients were included, with a median (interquartile range) age of 5 (2–11) months. Tidal volume was 5.8 (5.7–6.3) mL/kg, PEEP 8 (6–8), driving pressure 10 (8–11), and plateau pressure 17 (17–19) cm H2O. Forty‐one paired measurements were analyzed. PaCO2 was higher than PETCO2 (52 mmHg [48–54] vs. 42 mmHg [38–45], p < 0.01), and there were no significant differences with PLATCO2 (50 mmHg [46–55], p > 0.99). The concordance correlation coefficient and Spearman's correlation between PaCO2 and PLATCO2 were robust (ρc = 0.80 [95% confidence interval [CI]: 0.67–0.90]; and rho = 0.80, p < 0.001.), and for PETCO2 were weak and strong (ρc = 0.27 [95% CI: 0.15–0.38]; and rho = 0.63, p < 0.01). The bias between PLATCO2 and PaCO2 was −0.4 ± 3.5 mmHg (LoA −7.2 to 6.4), and between PETCO2 and PaCO2 was −8.5 ± 4.1 mmHg (LoA −16.6 to −0.5). The correlation between AVDSf and (S)AVDSf was moderate (rho = 0.55, p < 0.01), and the mean difference was −0.5 ± 5.6% (LoA −11.5 to 10.5) Conclusion: This pilot study showed the feasibility of measuring end‐tidal CO2 after a 3‐s end‐inspiratory breath hole in pediatric patients undergoing controlled ventilation for ARDS. Encouraging preliminary results warrant further study of this technique.Ítem La extubación durante la noche no se asocia con su fracaso en pacientes pediátricos de Unidad de Cuidados Intensivos: Estudio de cohorte retrospectivo(Sociedad Chilena de Pediatría, 2023-04-17) Ibarra V., Maybreet; Andrades E., Francisca; Satta S., María; Díaz, Franco; Donoso F., AlejandroPoco es conocido sobre la hora del día y carácter de éste (hábil/no hábil) en que se efectúa la extubación, y si durante la noche esta es segura. Objetivo: describir la frecuencia de extubación nocturna (EN) y en día no hábil (ENH). Adicionalmente determinar la asociación entre éstas y resultados clínicos. Pacientes y Método: Estudio de cohorte retrospectivo de pacientes menores de 18 años quienes recibieron ventilación mecánica (VM) invasiva y se efectuó un intento extubación en una Unidad de Paciente Crítico Pediátrico (UPCP) médico quirúrgica de alta complejidad entre el 01/01/2018 al 31/12/2021. Exposición primaria: EN, la cual fue definida como la realizada entre 20:01 - 8:00 horas. Se evaluó su asociación con fracaso de extubación (FE), duración de VM invasiva y tiempo de esta- día en la UPCP. Resultados: 146 pacientes fueron incluidos (58,9% hombres, edad 1,14 (0,25 - 5,5) años). En el 17,8% se efectuó EN. La extubación nocturna no se asoció con FE como tampoco el día de extubación. El FE fue 3,8% en EN y 5% en la extubación diurna (ED) (p = 0,80). La duración de la VM invasiva fue menor en EN que ED (48 (24-73,5) vs. 72 (48-96) h, p = 0,02). Conclusiones: La EN no se asoció con FE. Los pacientes con EN tuvieron menor duración de VM invasiva, y ésta última se asoció con FE. La retirada de la VM invasiva debe ser considerada en la primera oportunidad y estar determinada por factores clínicos, más que por la hora del día.Ítem Plateau pressure and driving pressure in volume- and pressure- controlled ventilation: comparison of frictional and viscoelastic resistive components in Pediatric Acute Respiratory Distress Syndrome(Society of Critical Care Medicine and The World Federation of Pediatric Intensive and Critical Care Societies, 2023-09) Cruces, Pablo; Moreno, Diego; Reveco, Sonia; Ramirez, Yennys; Díaz, FrancoObjectives: To examine frictional, viscoelastic, and elastic resistive components, as well threshold pressures, during volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV) in pediatric patients with acute respiratory distress syndrome (ARDS). Measurements and main results: All patients were in VCV mode during measurement of pulmonary mechanics, including: the first pressure drop (P1) upon reaching zero flow during the inspiratory hold, peak inspiratory pressure (PIP), plateau pressure (P PLAT ), and total positive end-expiratory pressure (tPEEP). We calculated the components of the working pressure, as defined by the following: frictional resistive = PIP-P1; viscoelastic resistive = P1-P PLAT ; purely elastic = driving pressure (ΔP) = P PLAT -tPEEP; and threshold = intrinsic PEEP. The procedures and calculations were repeated on PCV, keeping the same tidal volume and inspiratory time. Measurements in VCV were considered the gold standard. We performed Spearman correlation and Bland-Altman analysis. The median (interquartile range [IQR]) for patient age was 5 months (2-17 mo). Tidal volume was 5.7 mL/kg (5.3-6.1 mL/kg), PIP cm H 2 O 26 (23-27 cm H 2 O), P1 23 cm H 2 O (21-26 cm H 2 O), P PLAT 19 cm H 2 O (17-22 cm H 2 O), tPEEP 9 cm H 2 O (8-9 cm H 2 O), and ΔP 11 cm H 2 O (9-13 cm H 2 O) in VCV mode at baseline. There was a robust correlation (rho > 0.8) and agreement between frictional resistive, elastic, and threshold components of working pressure in both modes but not for the viscoelastic resistive component. The purely frictional resistive component was negligible. Median peak inspiratory flow with decelerating-flow was 21 (IQR, 15-26) and squared-shaped flow was 7 L/min (IQR, 6-10 L/min) ( p < 0.001). Conclusions: P PLAT , ΔP, and tPEEP can guide clinical decisions independent of the ventilatory mode. The modest purely frictional resistive component emphasizes the relevance of maintaining the same safety limits, regardless of the selected ventilatory mode. Therefore, peak inspiratory flow should be studied as a mechanism of ventilator-induced lung injury in pediatric ARDS