HER2-low and tumor infiltrating lymphocytes in triple-negative breast cancer: Are they connected?

Most patients with triple-negative breast cancer (TNBC) are not candidates for targeted therapy, leaving chemotherapy as the primary treatment option. Recently, immunotherapy has demonstrated promising results in TNBC, due to its immunogenicity. In addition, a novel antibody-drug conjugate, namely, trastuzumab-deruxtecan, has shown effectiveness in TNBC patients with low-HER2 expression (HER2-low). These novel treatment options raise the question about the potential association between the density of stromal tumor-infiltrating lymphocytes (sTILs) and the level of HER2 expression. We aimed to evaluate the association between the level of HER2 expression (HER2-low versus HER2-0) and density of sTILs in TNBC patients, and how they impact the response to neoadjuvant chemotherapy (NAC). This was a retrospective multicenter study including all TNBC patients diagnosed between 2018 and 2022. Central pathology review included sTILs percentages and level of HER2 expression. Tumors were reclassified as either HER2-0 (HER2 IHC 0) or HER2-low (IHC 1 + or 2 + with negative reflex test). Various clinicopathologic characteristics, including sTILs density, and response to NAC were compared between HER2-0 and HER2-low cases. In total, 753 TNBC patients were included in this study, of which 292 patients received NAC. Interobserver agreement between the original pathology report and central review was moderate (77% had the same IHC status after reclassification in either HER2-0 or HER2-low; k = 0.45). HER2-low TNBC represented about one third (36%) of the tumors. No significant difference in sTILs density or complete pathologic response rate was found between HER2-0 and HER2-low cases (p = 0.476 and p = 0.339, respectively). The density of sTILs (≥ 10% sTILs vs. < 10%) was independently associated with achieving a pCR (p = 0.011). In conclusion, no significant association was found between HER2-low status and density of sTILs nor response to NAC. Nonetheless, sTILs could be an independent biomarker for predicting NAC response in TNBC patients.

HER2-Low Breast Cancer: Incidence, Clinicopathologic Features, and Survival Outcomes From Real-World Data of a Large Nationwide Cohort.

Patients with breast cancer (BC) with low levels of human epidermal growth factor receptor 2 (HER2) expression (HER2-low) could benefit from novel antibody-drug conjugates. However, there is conflicting information regarding the characteristics of HER2-low BC and its outcome. We assessed the clinicopathologic characteristics and outcomes of HER2-low BC using real-world data from the Dutch National Pathology Registry. This retrospective study incorporated all patients with primary invasive BC, without neoadjuvant therapy, reported in the Dutch National Pathology Registry synoptic reporting module between 2014 and 2022. HER2 status was categorized as HER2-0 (defined as an immunohistochemistry score of 0 according to the current American Society of Clinical Oncology/College of American Pathologists guidelines) or HER2-low (immunohistochemistry score 1+ or 2+ without amplification). Clinicopathologic characteristics and overall survival of HER2-low BC were compared with HER2-0, adjusted for estrogen receptor (ER) status. We included 65,035 patients with BC, resulting in 69,424 tumors. The proportion of HER2-low BC was 62% in the ER+ cohort and 38% in the ER- cohort. A substantial number of patients had a different HER2 category between the needle biopsy and the corresponding surgical resection (28%) or among multiple tumors (28%). After multivariable logistic analysis, HER2-low tumors were significantly associated with histologic subtype, a higher ER, and lower progesterone receptor expression in the ER+ cohort, whereas within the ER-cohort, HER2-low tumors were associated with a lower tumor grade. However, the absolute differences were limited, and there was no significant difference in overall survival between HER2-low and HER2-0 tumors within the ER+ or ER- cohort. The classification of HER2 expression (HER2-0 vs HER2-low) varies between biopsies and corresponding resection specimens and within multiple tumors in the same patient, which could affect clinical decision making in case only HER2-low cases are eligible for novel HER2-targeting agents. The limited follow-up time and the lack of substantial clinicopathologic differences between HER2-low and HER2-0-cases could explain the lack of differences in overall survival.

Interobserver Variation in the Assessment of Immunohistochemistry Expression Levels in HER2-Negative Breast Cancer: Can We Improve the Identification of Low Levels of HER2 Expression by Adjusting the Criteria? An International Interobserver Study.

The classification of human epidermal growth factor receptor 2 (HER2) expression is optimized to detect HER2-amplified breast cancer (BC). However, novel HER2-targeting agents are also effective for BCs with low levels of HER2. This raises the question whether the current guidelines for HER2 testing are sufficiently reproducible to identify HER2-low BC. The aim of this multicenter international study was to assess the interobserver agreement of specific HER2 immunohistochemistry scores in cases with negative HER2 results (0, 1+, or 2+/in situ hybridization negative) according to the current American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines. Furthermore, we evaluated whether the agreement improved by redefining immunohistochemistry (IHC) scoring criteria or by adding fluorescent in situ hybridization (FISH). We conducted a 2-round study of 105 nonamplified BCs. During the first assessment, 16 pathologists used the latest version of the ASCO/CAP guidelines. After a consensus meeting, the same pathologists scored the same digital slides using modified IHC scoring criteria based on the 2007 ASCO/CAP guidelines, and an extra "ultralow" category was added. Overall, the interobserver agreement was limited (4.7% of cases with 100% agreement) in the first round, but this was improved by clustering IHC categories. In the second round, the highest reproducibility was observed when comparing IHC 0 with the ultralow/1+/2+ grouped cluster (74.3% of cases with 100% agreement). The FISH results were not statistically different between HER2-0 and HER2-low cases, regardless of the IHC criteria used. In conclusion, our study suggests that the modified 2007 ASCO/CAP criteria were more reproducible in distinguishing HER2-0 from HER2-low cases than the 2018 ASCO/CAP criteria. However, the reproducibility was still moderate, which was not improved by adding FISH. This could lead to a suboptimal selection of patients eligible for novel HER2-targeting agents. If the threshold between HER2 IHC 0 and 1+ is to be clinically actionable, there is a need for clearer, more reproducible IHC definitions, training, and/or development of more accurate methods to detect this subtle difference in protein expression levels.

Elastin in pulmonary pathology: relevance in tumours with a lepidic or papillary appearance. A comprehensive understanding from a morphological viewpoint.

Elastin and collagen are the main components of the lung connective tissue network, and together provide the lung with elasticity and tensile strength. In pulmonary pathology, elastin staining is used to variable extents in different countries. These uses include evaluation of the pleura in staging, and the distinction of invasion from collapse of alveoli after surgery (iatrogenic collapse). In the latter, elastin staining is used to highlight distorted but pre-existing alveolar architecture from true invasion. In addition to variable levels of use and experience, the interpretation of elastin staining in some adenocarcinomas leads to interpretative differences between collapsed lepidic patterns and true papillary patterns. This review aims to summarise the existing data on the use of elastin staining in pulmonary pathology, on the basis of literature data and morphological characteristics. The effect of iatrogenic collapse and the interpretation of elastin staining in pulmonary adenocarcinomas is discussed in detail, especially for the distinction between lepidic patterns and papillary carcinoma.

[Pediatric polygraphy: A 6-year experience]. / Poligrafía pediátrica: Experiencia de 6 años.

INTRODUCTION: The early diagnosis of Sleep Disordered Breathing (SDB) may allow proper intervention. Currently, polygraphy (PG) is a reliable and accessible alternative. OBJECTIVE: To describe and analyze the PG of children > 1 year old with suspicion of SDB. PATIENTS AND METHOD: PG of children > 1 year old and adolescents from Concepcion, Chile, with suspected SDB were included, from December 2011 to Au gust 2017. Demographic, clinical and polygraphic variables were collected. It was used descriptive sta tistics, expressing results in median and range. The association between apnea-hypopnea index (AHI) and oxygen saturation was determined by Spearman's Rho, considering significance of p < 0.05. Re sults: 190 studies were analyzed. Age 7.9 years old (1.0-20.6), 61% males. DIAGNOSIS: neuromuscular disease (NMD) (24.2%), chronic lung damage (21.1%), upper airway obstruction (UAO) (19.5%), neurological damage (11%), Down syndrome (8.9%), upper airway malformations (7.4%), central hypoventilation (3.7%), obesity (2.6%), and others (1.6%). 55.3% were altered PG, with 53.3% of mild Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS), 30.5% moderate, and 16.2% severe. There were no significant differences in AHI between groups of pathologies (p = 0.032), highlighting a higher AHI in obese patients 9 (0.41-51), and those with NMD 23.9 (0.4-36.6). It was found asso ciation between AHI and oxygen saturation parameters: mean saturation (rho = -0.425; p = 0.001), minimum (rho = -0.654; p = 0.001), and oxygen saturation below 90% (rho = 0.323; p = 0.001) in the whole sample. DISCUSSION: There was a high percentage of OSAHS in at-risk pediatric patients, especially in those with NMD and obesity. PG is an accessible and implementable tool in a public hospital, a situation that can potentially be extrapolated to other healthcare centers.

[Diagnosis of respiratory sleep disorders in newborns with suspected apneas: comparison between nocturnal saturometry and polygraphy]. / Diagnóstico de los trastornos respiratorios del sueño en recién nacidos con sospecha de apneas: comparación entre la saturometría nocturna y la poligrafía.

INTRODUCTION: Night Continuous Saturometry (CSO2) is used in Neonatal Units to detect events of hypoxemia in Newborns (NB) with apnea episodes. Polygraphy (PG) has a larger number of measuring channels. Our goal was to evaluate the diagnostic performance of CSO2 compared to Polygra phy in NB with suspected sleep apneas. PATIENTS AND METHOD: Results of CSO2 and PG performed simultaneously in RN with suspected apneas were retrospectively analyzed over a three-year period. A 2-channel Masimo Radical-7® pulse oximeter and an Apnea Link Plus® polygraph with 5 simulta neous recording channels were used. Altered PG was defined as: desaturation index under 80% per hour > 1 and/or number of desaturations under 80% > 20 seconds greater than one in the whole va lidated registry and/or hypoapnea apnea index > 1 event per hour. In parallel, altered SpO2C was de fined when one or both of the 80% saturation criteria were altered. Sensitivity, specificity, predictive values and Likelihood Ratio (LLR) for CSO2 were calculated. Results were expressed in absolute value, with 95% confidence interval. RESULTS: Simultaneous 40 CSO2 and PG were performed; 80% (32/40) of them were preterm infants, 60% (24/40) males. 38% (15/40) of the CSO2 and 15% (6/40) of the PGs were altered (p < 0.05). CSO2 has a 100% Sensitivity, 74% Specificity, 40% VPP, 100% VPN, LLR + 3.78 and LLR-0. CONCLUSION: In the studied NB, CSO2 has a high diagnostic value, however, it may present false positives; It is suggested to use as a screening method and to perform diagnostic confirmation with another sleep test, such as PG.

HER2-low breast cancer and response to neoadjuvant chemotherapy: a population-based cohort study.

About half of breast cancers (BC) without amplification of the human epidermal growth factor receptor 2 (HER2) have a low HER2 protein expression level (HER2-low). The clinical impact of HER2-low and the response to neoadjuvant chemotherapy (NAC) is unclear. This study aimed to assess the association between HER2-low BC and pathological response to NAC. Data from the Dutch Pathology Registry were collected for 11,988 BC patients treated with NAC between 2014 and 2022. HER2-low BC was defined as an immunohistochemical score of 1+ or 2+ and a negative molecular reflex test. We compared clinicopathological features of HER2-0 versus HER2-low BC and assessed the correlation between HER2 status and the pathological complete response (pCR) rate after NAC, including overall survival. Among hormone receptor (HR)-positive tumours, 67% (n=4,619) were HER2-low, compared to 47% (n=1,167) in the HR-negative group. Around 32% (n=207) of patients had a discordant HER2 status between the pre-NAC biopsy and the corresponding post-NAC resection, within which 87% (n=165) changed from HER2-0 to HER2-low or vice versa. The pCR rate was significantly lower in HER2-low BC compared to HER2-0 BC within the HR-positive group (4% versus 5%; p=0.022). However, the absolute difference was limited, so the clinical relevance is questionable. In HR-negative cases, the difference in pCR was not significant (32% versus 34%; p=0.266). No significant difference in overall survival was observed between HER2-low and HER2-0 tumours, regardless of hormone receptor status. The antibody-drug conjugate trastuzumab deruxtecan (T-DXd) has improved survival outcomes of patients with HER2-low metastatic BC. The finding that one-third of the patients in this study had a discordant HER2 status between the pre-NAC biopsy and the post-NAC resection specimen could impact clinical decision-making should T-DXd be used in early BC treatment.

Selecting patients with HER2-low breast cancer: Getting out of the tangle.

The promising effect of antibody-drug conjugates on breast cancer with low expression of HER2 (HER2-low) raises many questions regarding the optimal selection of patients for this treatment. A key question is whether HER2 immunohistochemistry, an assay optimised to detect HER2 amplification, is reliable enough to assess HER2 protein levels to select patients with HER2-low breast cancer in daily pathology practices worldwide. Moreover, whether this assessment can be performed with sufficient reproducibility between pathologists in daily practices is debatable. Herein, we address the historical track record of the CAP-ASCO HER2 Guidelines, the reported limited reproducibility by pathologists of HER2 immunohistochemistry in the non-amplified cases, and the performance variation of different antibodies. Based on this summary, we propose solutions to improve the robustness to enable reliable identification of patients with HER2-low breast cancer.

Experience in a Pediatric Prolonged Mechanical Ventilation Unit from a public hospital in Chile. / Experiencia de una Unidad de Ventilación Mecánica Pediátrica Prolongada en un hospital público de Chile.

INTRODUCTION: Hospitalized patients with high respiratory technology dependency are increasingly common and result in lengthy stays in intensive care units. Strategies mitigating its impact have been scarcely described. OBJECTIVE: To describe a 6-year experience in a Pediatric Prolonged Mechanical Ventilation Unit. METHODS: Retrospective study. All children admitted to the unit between October 2012 and December 2018 were included. Descriptive and inferential statistical methods were used, analyzing lengths of stay and readmissions. Different outcome measures were compared according to the type of pathology and mechanical ventilation. RESULTS: A total of 113 patients had 310 admissions to the unit. Age at admission: 2.2 years (0.6-8.8); males: 60.2 %. PATHOLOGIES: neuromuscular disease (22.1 %), chronic lung disease (20.4 %), neurological damage (34.5 %), upper airway obstruction (9.7 %), heart disease (3.5 %), Down syndrome (9.7 %). A total of 10 507 bed-days were used; with a 92.6 % occupancy rate, 54.8 % of transfers to the intensive care unit, and 66.1 % of readmissions. Mean length of stay: 16 days (6.5- 49.0); differences in age at admission observed by pathology (p = 0.032). More readmissions were observed in children with neurological damage and Down syndrome (p = 0.004). Children with invasive ventilation were observed to have a longer length of stay (p < 0.001) and more readmissions (p < 0.001). CONCLUSION: The occupancy rate at the PMVU was over 90 %, which allowed more available intensive care beds and discharging all patients. Children with invasive ventilation had a longer length of stay and more readmissions.

Introducción: Los pacientes hospitalizados con altas dependencias tecnológicas respiratorias son cada vez más frecuentes y generan largas estadías en unidades de cuidados intensivos. Las estrategias que mitiguen su impacto han sido escasamente descritas. Objetivo: Describir 6 años de experiencia de una Unidad de Ventilación Mecánica Prolongada Pediátrica. Métodos: Estudio retrospectivo. Se incluyeron todos los niños ingresados a la Unidad entre 10-2012 y 12-2018. Se realizó estadística descriptiva e inferencial, analizando tiempos de hospitalización y reingresos. Se compararon distintas variables según tipo de patología y ventilación mecánica. Resultados: 113 pacientes registraron 310 ingresos a la Unidad. Edad de ingreso: 2,2 años (0,6-8,8); varones: el 60,2 %. Patologías: enfermedad neuromuscular (el 22,1 %), enfermedad pulmonar crónica (el 20,4 %), daño neurológico (el 34,5 %), obstrucción de vía aérea superior (el 9,7 %), cardiopatía (el 3,5 %), síndrome de Down (el 9,7 %). Se utilizaron 10 507 días/cama; con índice ocupacional del 92,6 %, el 54,8 % de traslados a la Unidad de Cuidados Intensivos y el 66,1 % de reingresos. Hospitalización media: 16 días (6,5-49,0); diferencias en edad de ingreso según patologías (p = 0,032). Hubo más reingresos en niños con daño neurológico y síndrome de Down (p = 0,004). Los niños con asistencia ventilatoria invasiva presentaron más días de hospitalización (p < 0,001) y reingresos (p < 0,001). Conclusión: El índice ocupacional fue superior al 90 %; permitió mayor disponibilidad de camas intensivas y egresar a todos los pacientes. Los niños con asistencia ventilatoria invasiva se hospitalizaron más tiempo y reingresaron más.

Pediatric pulmonary rehabilitation program at a Chilean public hospital. / Programa de rehabilitación respiratoria infantil en un hospital público de Chile.

INTRODUCTION: Pediatric pulmonary rehabilitation is relevant in the management of chronic respiratory diseases. In Chile, it is provided only at certain hospitals. Objective. To describe the outcomes of a pediatric pulmonary rehabilitation program after 3 months of rehabilitation. METHODOLOGY: Retrospective study of patients with chronic lung disease, neuromuscular disease, and other chronic conditions admitted to the program between June 2011 and June 2017. Assessments included general physical and respiratory muscle examination, and spirometry. General physical training and respiratory muscle training were planned according to facilitybased, mixed and home protocols. RESULTS: A total of 156 patients (11.45 ± 3.55 years old) were included, 68 had chronic lung disease (11.56 ± 4.6 years old, 43.5 %); 45, neuromuscular disease (11.4 ± 3.7 years old, 28.8 %); and 43, various chronic conditions (11.31 ± 3.9 years old). Out of all patients, 102 (65.4 %) followed training protocols; targeted (n = 27), mixed (n = 23), and home (n = 50); compliance was 69 %, 87.5 %, and 70 %, respectively. Peak inspiratory pressure increased by 19.3 % (p = 0.001); peak expiratory pressure, 14.5 % (p = 0.001); forced vital capacity, 12.9 % (p = 0.001); forced expiratory volume in 1 second, 11.6 % (p = 0.004); and the six-minute walk test, 17.6 meters (p = 0.036) after 3 months of rehabilitation. CONCLUSIONS: The intervention protocol improved cardiorespiratory functional capacity. Compliance was over 65 %.

Introducción. La rehabilitación respiratoria infantil es relevante en el manejo de enfermedades respiratorias crónicas. En Chile, se desarrolla solo en algunos hospitales. Objetivo. Describir los resultados de un programa de rehabilitación respiratoria infantil tras 3 meses de rehabilitación. Metodología. Estudio retrospectivo de los pacientes con enfermedad pulmonar crónica, enfermedad neuromuscular y otras patologías crónicas admitidos desde junio de 2011 a junio de 2017. Se realizó evaluación física general, evaluación de musculatura respiratoria y espirometría. Se planificó entrenamiento físico general y entrenamiento muscular respiratorio, con protocolos institucional, mixto y domiciliario. Resultados. Ingresaron al programa 156 pacientes (11,45 ± 3,55 años), 68 con enfermedad pulmonar crónica (11,56 ± 4,6 años, el 43,5 %), 45 con enfermedad neuromuscular (11,4 ± 3,7 años, el 28,8 %) y 43 con patologías crónicas diversas (11,31 ± 3,9 años). Del total, se entrenaron 102 (el 65,4 %); dirigido (n = 27), mixto (n = 23) y domiciliario (n = 50) con adherencia del 69 %, del 87,5 % y del 70 %, respectivamente. Aumentó el 19,3 % la presión inspiratoria máxima (p = 0,001), el 14,5 % la presión espiratoria máxima (p = 0,001), el 12,9 % la capacidad vital forzada (p = 0,001), el 11,6 % el volumen espiratorio forzado al primer segundo (p = 0,004) y 17,6 metros en el test de marcha de 6 minutos (p = 0,036) tras 3 meses de rehabilitación. Conclusiones. El protocolo de intervención incrementó el estatus funcional cardiorrespiratorio. La adherencia fue superior al 65 %.

Effect of abdominal muscle training on respiratory muscle strength and forced expiratory flows in sedentary, healthy adolescents. / Efecto del entrenamiento de músculos abdominales sobre la fuerza muscular respiratoria y flujos espiratorios forzados en adolescentes sanos sedentarios.

INTRODUCTION: Respiratory muscle training is the most commonly used method to revert respiratory muscle weakness; however, the effect of protocols based on non-respiratory maneuvers has not been adequately studied in the pediatric population. The objective of this study was to establish the effect of abdominal muscle training on respiratory muscle strength and forced expiratory flows in healthy adolescents. METHODS: This was a quasi-experiment. The sample was made up of healthy adolescents divided into two groups: an experimental group who completed eight weeks of active abdominal muscle training, and an equivalent control group. The following indicators were measured: abdominal muscle strength, maximal inspiratory pressure, maximal expiratory pressure (MEP), peak expiratory flow, and peak cough flow, before and after protocol completion. A value of p < 0.05 was considered significant. RESULTS: All studied outcome measures increased significantly in the experimental group but only MEP increased in the control group. In addition, a higher MEP was observed in the experimental group compared to the control group at the end of the protocol, together with a greater increase in MEP and peak expiratory flow. Finally, the increase in MEP was associated with an increase in cough peak flow in the experimental group but not in the control group. CONCLUSION: After eight weeks of abdominal muscle training, MEP and peak expiratory flow increased in healthy (sedentary) adolescents. Such effects were associated with intervention-induced increases in cough peak flow.

INTRODUCCIÓN: El entrenamiento muscular respiratorio es el método más utilizado para revertir la debilidad muscular respiratoria; no obstante, el efecto de protocolos basados en maniobras no respiratorias no ha sido suficientemente estudiado en población pediátrica. El objetivo de este estudio fue determinar el efecto del entrenamiento de la musculatura abdominal sobre la fuerza de los músculos respiratorios y los flujos espiratorios forzados en adolescentes sanos. MÉTODOS: Estudio cuasiexperimental. La muestra estuvo integrada por adolescentes sanos divididos en dos grupos: un grupo experimental, quienes realizaron 8 semanas de entrenamiento de la musculatura abdominal activo, y un grupo control equivalente. Se midió la fuerza de los músculos abdominales, la presión inspiratoria máxima, la presión espiratoria máxima (PeMax), el flujo espiratorio máximo y el flujo máximo de tos antes y después del protocolo. Se consideró significativo un valor de p < 0,05. RESULTADOS: Todas las variables estudiadas aumentaron significativamente en el grupo experimental; sin embargo, solo la PeMax se incrementó en el grupo control. Adicionalmente, el grupo experimental presentó una mayor PeMax que el grupo control al final del protocolo, así como también una mayor ganancia en la PeMax y flujo espiratorio máximo. Finalmente, el incremento en la PeMax se asoció con el aumento en el flujo máximo de tos en el grupo experimental, lo que no fue observado en el grupo control. CONCLUSIÓN: En 8 semanas de entrenamiento de la musculatura abdominal, se logró incrementar la PeMax y el flujo espiratorio máximo en adolescentes sanos (sedentarios). Estos efectos se asociaron a incrementos en el flujo máximo de tos inducidos por la intervención.

Experiencia de una Unidad de Ventilación Mecánica Pediátrica Prolongada en un hospital público de Chile / Experience in a Pediatric Prolonged Mechanical Ventilation Unit from a public hospital in Chile

Introducción: Los pacientes hospitalizados con altas dependencias tecnológicas respiratorias son cada vez más frecuentes y generan largas estadías en unidades de cuidados intensivos. Las estrategias que mitiguen su impacto han sido escasamente descritas. Objetivo: Describir 6 años de experiencia de una Unidad de Ventilación Mecánica Prolongada Pediátrica.Métodos: Estudio retrospectivo. Se incluyeron todos los niños ingresados a la Unidad entre 10-2012 y 12-2018. Se realizó estadística descriptiva e inferencial, analizando tiempos de hospitalización y reingresos. Se compararon distintas variables según tipo de patología y ventilación mecánica.Resultados: 113 pacientes registraron 310 ingresos a la Unidad. Edad de ingreso: 2,2 años (0,6-8,8); varones: el 60,2 %. Patologías: enfermedad neuromuscular (el 22,1 %), enfermedad pulmonar crónica (el 20,4 %), daño neurológico (el 34,5 %), obstrucción de vía aérea superior (el 9,7 %), cardiopatía (el 3,5 %), síndrome de Down (el 9,7 %). Se utilizaron 10 507 días/cama; con índice ocupacional del 92,6 %, el 54,8 % de traslados a la Unidad de Cuidados Intensivos y el 66,1 % de reingresos. Hospitalización media: 16 días (6,5-49,0); diferencias en edad de ingreso según patologías (p = 0,032). Hubo más reingresos en niños con daño neurológico y síndrome de Down (p = 0,004). Los niños con asistencia ventilatoria invasiva presentaron más días de hospitalización (p < 0,001) y reingresos (p < 0,001).Conclusión: El índice ocupacional fue superior al 90 %; permitió mayor disponibilidad de camas intensivas y egresar a todos los pacientes. Los niños con asistencia ventilatoria invasiva se hospitalizaron más tiempo y reingresaron más

Introduction: Hospitalized patients with high respiratory technology dependency are increasingly common and result in lengthy stays in intensive care units. Strategies mitigating its impact have been scarcely described.Objective: To describe a 6-year experience in a Pediatric Prolonged Mechanical Ventilation Unit.Methods: Retrospective study. All children admitted to the unit between October 2012 and December 2018 were included. Descriptive and inferential statistical methods were used, analyzing lengths of stay and readmissions. Different outcome measures were compared according to the type of pathology and mechanical ventilation.Results: A total of 113 patients had 310 admissions to the unit. Age at admission: 2.2 years (0.6-8.8); males: 60.2 %. Pathologies: neuromuscular disease (22.1 %), chronic lung disease (20.4 %), neurological damage (34.5 %), upper airway obstruction (9.7 %), heart disease (3.5 %), Down syndrome (9.7 %). A total of 10 507 bed-days were used; with a 92.6 % occupancy rate, 54.8 % of transfers to the intensive care unit, and 66.1 % of readmissions. Mean length of stay: 16 days (6.5-49.0); differences in age at admission observed by pathology (p = 0.032). More readmissions were observed in children with neurological damage and Down syndrome (p = 0.004). Children with invasive ventilation were observed to have a longer length of stay (p < 0.001) and more readmissions (p < 0.001).Conclusion: The occupancy rate at the PMVU was over 90 %, which allowed more available intensive care beds and discharging all patients. Children with invasive ventilation had a longer length of stay and more readmissions.

Programa de rehabilitación respiratoria infantil en un hospital público de Chile / Pediatric pulmonary rehabilitation program at a Chilean public hospital

Introducción. La rehabilitación respiratoria infantil es relevante en el manejo de enfermedades respiratorias crónicas. En Chile, se desarrolla solo en algunos hospitales.Objetivo. Describir los resultados de un programa de rehabilitación respiratoria infantil tras 3 meses de rehabilitación.Metodología. Estudio retrospectivo de los pacientes con enfermedad pulmonar crónica, enfermedad neuromuscular y otras patologías crónicas admitidos desde junio de 2011 a junio de 2017. Se realizó evaluación física general, evaluación de musculatura respiratoria y espirometría. Se planificó entrenamiento físico general y entrenamiento muscular respiratorio, con protocolos institucional, mixto y domiciliario.Resultados. Ingresaron al programa 156 pacientes (11,45 ± 3,55 años), 68 con enfermedad pulmonar crónica (11,56 ± 4,6 años, el 43,5 %), 45 con enfermedad neuromuscular (11,4 ± 3,7 años, el 28,8 %) y 43 con patologías crónicas diversas (11,31 ± 3,9 años). Del total, se entrenaron 102 (el 65,4 %); dirigido (n = 27), mixto (n = 23) y domiciliario (n = 50) con adherencia del 69 %, del 87,5 % y del 70 %, respectivamente. Aumentó el 19,3 % la presión inspiratoria máxima (p = 0,001), el 14,5 % la presión espiratoria máxima (p = 0,001), el 12,9 % la capacidad vital forzada (p = 0,001), el 11,6 % el volumen espiratorio forzado al primer segundo (p = 0,004) y 17,6 metros en el test de marcha de 6 minutos (p = 0,036) tras 3 meses de rehabilitación.Conclusiones. El protocolo de intervención incrementó el estatus funcional cardiorrespiratorio. La adherencia fue superior al 65 %.

Introduction. Pediatric pulmonary rehabilitation is relevant in the management of chronic respiratory diseases. In Chile, it is provided only at certain hospitals.Objective. To describe the outcomes of a pediatric pulmonary rehabilitation program after 3 months of rehabilitation.Methodology. Retrospective study of patients with chronic lung disease, neuromuscular disease, and other chronic conditions admitted to the program between June 2011 and June 2017. Assessments included general physical and respiratory muscle examination, and spirometry. General physical training and respiratory muscle training were planned according to facility-based, mixed and home protocols. Results. A total of 156 patients (11.45 ± 3.55 years old) were included, 68 had chronic lung disease (11.56 ± 4.6 years old, 43.5 %); 45, neuromuscular disease (11.4 ± 3.7 years old, 28.8 %); and 43, various chronic conditions (11.31 ± 3.9 years old). Out of all patients, 102 (65.4 %) followed training protocols; targeted (n = 27), mixed (n = 23), and home (n = 50); compliance was 69 %, 87.5 %, and 70 %, respectively. Peak inspiratory pressure increased by 19.3 % (p = 0.001); peak expiratory pressure,14.5 % (p = 0.001); forced vital capacity, 12.9 % (p = 0.001); forced expiratory volume in 1 second, 1.6 % (p = 0.004); and the six-minute walk test, 17.6 meters (p = 0.036) after 3 months of rehabilitation.Conclusions. The intervention protocol improved cardiorespiratory functional capacity. Compliance was over 65 %.

Poligrafía pediátrica: experiencia de 6 años / Pediatric polygraphy: a 6-year experience

INTRODUCCIÓN: El diagnóstico precoz de los Trastornos Respiratorios del Sueño (TRS) puede permitir una intervención oportuna. La poligrafía (PG) es una alternativa confiable y accesible en la actualidad. OBJETIVO: Describir y analizar PG de niños > 1 año con sospecha de TRS. PACIENTES Y MÉTODO: Se incluyeron PG de niños y adolescentes > 1 año de edad con sospecha de TRS, desde diciembre de 2011 hasta agosto de 2017 provenientes de la ciudad de Concepcion, Chile. Se recopilaron datos demo gráficos, clínicos y variables poligráficas. Estadística descriptiva, expresando resultados en mediana y rango. Se determinó asociación entre índice de apnea hipopnea (IAH) y saturación mediante Rho de Spearman; considerando significancia p < 0,05. RESULTADOS: Se analizaron 190 estudios. Edad 7,9 años (1,0-20,6), varones 61%. Diagnósticos: enfermedades neuromusculares (ENM) (24,2%), daño pulmonar crónico (21,1%), obstrucción de vía aérea superior (OVAS) (19,5%), daño neurológico (11%), síndrome de Down (8,9%) malformaciones VAS (7,4%), hipoventilación central (3,7%), obesidad (2,6%) y otros (1,6%). El 55,3% de las PG resultaron alteradas; síndrome de apnea hipopnea obstructiva del sueño (SAHOS) leve en 53,3%, moderado 30,5% y severo 16,2%. No se observaron diferencias significativas en IAH entre grupos de patologías (p = 0,032), destacando un mayor IAH en Obesidad 9,0 (0,41-51) y ENM 23,9 (0,4-36,6). Se constató asociación entre IAH y parámetros de saturación; saturación promedio (rho = -0,425; p = 0,001); mínima (rho = -0,654; p = 0,001); y saturación bajo 90% (rho = 0,323; p = 0,001) en la totalidad de la muestra. DISCUSIÓN: Existió un alto porcentaje de SAHOS en pacientes pediátricos de riesgo, en especial en aquellos con ENM y obesidad. La PG es una herramienta accesible e implementable en un hospital público; situación potencialmente extrapolable a otros centros asistenciales.

INTRODUCTION: The early diagnosis of Sleep Disordered Breathing (SDB) may allow proper intervention. Currently, polygraphy (PG) is a reliable and accessible alternative. OBJECTIVE: To describe and analyze the PG of children > 1 year old with suspicion of SDB. PATIENTS AND METHOD: PG of children > 1 year old and adolescents from Concepcion, Chile, with suspected SDB were included, from December 2011 to August 2017. Demographic, clinical and polygraphic variables were collected. It was used descriptive sta tistics, expressing results in median and range. The association between apnea-hypopnea index (AHI) and oxygen saturation was determined by Spearman's Rho, considering significance of p < 0.05. RESULTS: 190 studies were analyzed. Age 7.9 years old (1.0-20.6), 61% males. Diagnosis: neuromuscular disease (NMD) (24.2%), chronic lung damage (21.1%), upper airway obstruction (UAO) (19.5%), neurological damage (11%), Down syndrome (8.9%), upper airway malformations (7.4%), central hypoventilation (3.7%), obesity (2.6%), and others (1.6%). 55.3% were altered PG, with 53.3% of mild Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS), 30.5% moderate, and 16.2% severe. There were no significant differences in AHI between groups of pathologies (p = 0.032), highlighting a higher AHI in obese patients 9 (0.41-51), and those with NMD 23.9 (0.4-36.6). It was found asso ciation between AHI and oxygen saturation parameters: mean saturation (rho = -0.425; p = 0.001), minimum (rho = -0.654; p = 0.001), and oxygen saturation below 90% (rho = 0.323; p = 0.001) in the whole sample. DISCUSSION: There was a high percentage of OSAHS in at-risk pediatric patients, especially in those with NMD and obesity. PG is an accessible and implementable tool in a public hospital, a situation that can potentially be extrapolated to other healthcare centers.

Diagnóstico de los trastornos respiratorios del sueño en recién nacidos con sospecha de apneas: comparación entre la saturometría nocturna y la poligrafía / Diagnosis of respiratory sleep disorders in newborns with suspected apneas: comparison between nocturnal saturometry and polygraphy

Resumen Introducción: La Saturometría Nocturna Continua (SpChC), es utilizada en Unidades de Neonato logia para detección de eventos de hipoxemia en Recién Nacidos (RN) con episodios de apneas. La Poligrafía (PG) presenta un número mayor de canales de medición. El objetivo fue evaluar el rendi miento diagnóstico de la SpOhC respecto a la Poligrafía en RN con sospecha de apneas. Pacientes y Método: Se analizaron retrospectivamente resultados de SpOhC y PG realizadas en forma simultáneas en RN con sospecha de apneas, en un periodo de tres años. Se utilizó un saturómetro Masimo Radi-cal-7® con 2 canales y un polígrafo Apnea Link Plus® con 5 canales de registro simultáneos. Se con sideró PG alterada: índice de desaturaciones bajo 80% por hora > a 1 y/o número de desaturaciones bajo 80% > 20 segundos mayor a uno en todo el registro validado y/o índice de apnea hipoapnea > a 1 evento por hora. Paralelamente, se definió SpOhC alterada cuando uno o ambos de los criterios de saturometria bajo 80%, estaban alterados. Se calcularon valores de sensibilidad, especificidad, valores predictivos y Likelihood Ratio (LLR) para la SpÜ2C. Los resultados se expresaron en valor absoluto, con 95% de intervalo de confianza. Resultados: Se realizaron 40 SpÜ2C y PG simultáneos; un 80% (32/40) de ellos fueron RN prematuros, 60% (24/40) varones. Un 38% (15/40) de las SpOhC y un 15% (6/40) de las PG resultaron alteradas (p < 0,05). La SpÜ2C presenta una Sensibilidad 100%, Especificidad 74%, El VPP 40%, VPN 100%, LLR + 3,78 y LLR-0. Conclusión: En los RN estudiados, la SpC2C posee un alto valor diagnóstico, sin embargo, puede presentar falsos positivos; por lo cual se sugiere utilizar como método de tamizaje y realizar confirmación diagnóstica con otro examen de sueño, como la PG.

Abstract Introduction: Night Continuous Saturometry (CSO2) is used in Neonatal Units to detect events of hypoxemia in Newborns (NB) with apnea episodes. Polygraphy (PG) has a larger number of measuring channels. Our goal was to evaluate the diagnostic performance of CSO2 compared to Polygra phy in NB with suspected sleep apneas. Patients and Method: Results of CSO2 and PG performed simultaneously in RN with suspected apneas were retrospectively analyzed over a three-year period. A 2-channel Masimo Radical-7® pulse oximeter and an Apnea Link Plus® polygraph with 5 simulta neous recording channels were used. Altered PG was defined as: desaturation index under 80% per hour > 1 and/or number of desaturations under 80% > 20 seconds greater than one in the whole va lidated registry and/or hypoapnea apnea index > 1 event per hour. In parallel, altered SpO2C was de fined when one or both of the 80% saturation criteria were altered. Sensitivity, specificity, predictive values and Likelihood Ratio (LLR) for CSO2 were calculated. Results were expressed in absolute value, with 95% confidence interval. Results: Simultaneous 40 CSO2 and PG were performed; 80% (32/40) of them were preterm infants, 60% (24/40) males. 38% (15/40) of the CSO2 and 15% (6/40) of the PGs were altered (p < 0.05). CSO2 has a 100% Sensitivity, 74% Specificity, 40% VPP, 100% VPN, LLR + 3.78 and LLR-0. Conclusion: In the studied NB, CSO2 has a high diagnostic value, however, it may present false positives; It is suggested to use as a screening method and to perform diagnostic confirmation with another sleep test, such as PG.

Efecto del entrenamiento de músculos abdominales sobre la fuerza muscular respiratoria y flujos espiratorios forzados en adolescentes sanos sedentarios / Effect of abdominal muscle training on respiratory muscle strength and forced expiratory flows in sedentary, healthy adolescents

Introducción. El entrenamiento muscular respiratorio es el método más utilizado para revertir la debilidad muscular respiratoria; no obstante, el efecto de protocolos basados en maniobras no respiratorias no ha sido suficientemente estudiado en población pediátrica. El objetivo de este estudio fue determinar el efecto del entrenamiento de la musculatura abdominal sobre la fuerza de los músculos respiratorios y los flujos espiratorios forzados en adolescentes sanos. Métodos. Estudio cuasiexperimental. La muestra estuvo integrada por adolescentes sanos divididos en dos grupos: un grupo experimental, quienes realizaron 8 semanas de entrenamiento de la musculatura abdominal activo, y un grupo control equivalente. Se midió la fuerza de los músculos abdominales, la presión inspiratoria máxima, la presión espiratoria máxima (PeMax), el flujo espiratorio máximo y el flujo máximo de tos antes y después del protocolo. Se consideró significativo un valor de p < 0,05. Resultados. Todas las variables estudiadas aumentaron significativamente en el grupo experimental; sin embargo, solo la PeMax se incrementó en el grupo control. Adicionalmente, el grupo experimental presentó una mayor PeMax que el grupo control al final del protocolo, así como también una mayor ganancia en la PeMax y flujo espiratorio máximo. Finalmente, el incremento en la PeMax se asoció con el aumento en el flujo máximo de tos en el grupo experimental, lo que no fue observado en el grupo control. Conclusión. En 8 semanas de entrenamiento de la musculatura abdominal, se logró incrementar la PeMax y el flujo espiratorio máximo en adolescentes sanos (sedentarios). Estos efectos se asociaron a incrementos en el flujo máximo de tos inducidos por la intervención.

Introduction. Respiratory muscle training is the most commonly used method to revert respiratory muscle weakness; however, the effect of protocols based on non-respiratory maneuvers has not been adequately studied in the pediatric population. The objective of this study was to establish the effect of abdominal muscle training on respiratory muscle strength and forced expiratory flows in healthy adolescents. Methods. This was a quasi-experiment. The sample was made up of healthy adolescents divided into two groups: an experimental group who completed eight weeks of active abdominal muscle training, and an equivalent control group. The following indicators were measured: abdominal muscle strength, maximal inspiratory pressure, maximal expiratory pressure (MEP), peak expiratory flow, and peak cough flow, before and after protocol completion. A value of p < 0.05 was considered significant. Results. All studied outcome measures increased significantly in the experimental group but only MEP increased in the control group. In addition, a higher MEP was observed in the experimental group compared to the control group at the end of the protocol, together with a greater increase in MEP and peak expiratory flow. Finally, the increase in MEP was associated with an increase in cough peak flow in the experimental group but not in the control group. Conclusion. After eight weeks of abdominal muscle training, MEP and peak expiratory flow increased in healthy (sedentary) adolescents. Such effects were associated with intervention-induced increases in cough peak flow.

Effects of exercise training on smoking-induced cardiopulmonary diseases. A review of the physiological mechanisms / Efectos del entrenamiento físico en la enfermedad cardiopulmonar inducida por el tabaquismo: revisión de los mecanismos fisiológicos

OBJECTIVE: Cigarette smoking triggers a plethora of biological mechanisms that promote the development of cardiovascular and respiratory diseases. Some preclinical studies have shown that exercise training could be effective in blunting oxidative stress and inflammatory response induced by cigarette smoking. Therefore, we aim to analyze the effect of exercise training on pulmonary and cardiovascular system in experimental models of cigarette smoking. METHODS: A systematic search was performed in order to identify studies addressed to evaluate the effects of exercise training on pulmonary and/or cardiovascular damage induced by cigarette smoking in animal models. RESULTS: fourteen articles were identified, all of them performed in rats or mice. Running and swimming were the only training methods and whole-body smoke exposition was the most prevalent smoking protocol used in the studies. CONCLUSION: The studies support the hypothesis that exercise training performed before, concurrently or after smoking can blunt or even revert the oxidative stress and inflammatory response in animals exposed to cigarette smoke, which could contribute to recovering its cardiovascular and respiratory function

OBJETIVO: El tabaquismo desencadena diversos mecanismos biológicos que producen el desarrollo de enfermedades cardiovasculares y pulmonares. Algunos estudios preclínicos han demostrado que el entrenamiento físico puede ser eficaz en la reducción del estrés oxidativo y de la respuesta inflamatoria inducida por el tabaquismo. Por tanto, nuestro objetivo ha sido analizar el efecto del entrenamiento físico en los sistemas pulmonar y cardiovascular en modelos experimentales de tabaquismo. MÉTODO: Se realizo una búsqueda sistemática para localizar estudios orientados al análisis de los efectos del entrenamiento físico sobre los daños pulmonares y/o cardiovasculares inducidos por el tabaquismo en modelos animales. RESULTADOS: Se identificaron catorce estudios, todos realizados en ratas o ratones. Correr o nadar fueron los únicos métodos de entrenamiento y la exposición de cuerpo entero al humo del tabaco fue el protocolo de tabaquismo mas frecuentemente usado en los estudios. CONCLUSIÓN: Los estudios sustentan la hipótesis de que el entrenamiento físico realizado antes, durante o después del tabaquismo, puede reducir o incluso revertir, el estrés oxidativo y la respuesta inflamatoria en animales expuestos al humo del tabaco, lo que podría contribuir en la recuperación de la función cardiovascular y respiratoria