Artículos Medicina y Ciencias de la Salud

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Distinct Driver Pathway Enrichments and a High Prevalence of TSC2 Mutations in Right Colon Cancer in Chile: A Preliminary Comparative Analysis
(2024) Tapia, Camilo; Valenzuela, Guillermo; González, Evelin; Maureira, Ignacio; Toro, Jessica; Freire, Matías; Sepúlveda, Gonzalo; Ampuero, Diego; Blanco, Alejandro; Gallegos, Iván; Morales, Fernanda; Erices, José; Barajas, Olga; Ahumada, Mónica; Contreras, Héctor; González, Jaime; Armisén, Ricardo; Marcelain, Katherine
Colorectal cancer (CRC) is the second leading cause of cancer deaths globally. While ethnic differences in driver gene mutations have been documented, the South American population remains understudied at the genomic level, despite facing a rising burden of CRC. We analyzed tumors of 40 Chilean CRC patients (Chp) using next-generation sequencing and compared them to data from mainly Caucasian cohorts (TCGA and MSK-IMPACT). We identified 388 mutations in 96 out of 135 genes, with TP53 (45%), KRAS (30%), PIK3CA (22.5%), ATM (20%), and POLE (20%) being the most frequently mutated. TSC2 mutations were associated with right colon cancer (44.44% in RCRC vs. 6.45% in LCRC, p-value = 0.016), and overall frequency was higher compared to TCGA (p-value = 1.847 × 10-5) and MSK-IMPACT cohorts (p-value = 3.062 × 10-2). Limited sample size restricts definitive conclusions, but our data suggest potential differences in driver mutations for Chilean patients, being that the RTK-RAS oncogenic pathway is less affected and the PI3K pathway is more altered in Chp compared to TCGA (45% vs. 25.56%, respectively). The prevalence of actionable pathways and driver mutations can guide therapeutic choices, but can also impact treatment effectiveness. Thus, these findings warrant further investigation in larger Chilean cohorts to confirm these initial observations. Understanding population-specific driver mutations can guide the development of precision medicine programs for CRC patients.
A Comprehensive Analysis of the Effect of A>I(G) RNA-Editing Sites on Genotoxic Drug Response and Progression in Breast Cancer
(2024) Bernal, Yanara; Blanco, Alejandro; Sagredo, Eduardo; Oróstica, Karen; Alfaro, Ivan; Marcelain, Katherine; Armisén, Ricardo
Dysregulated A>I(G) RNA editing, which is mainly catalyzed by ADAR1 and is a type of post-transcriptional modification, has been linked to cancer. A low response to therapy in breast cancer (BC) is a significant contributor to mortality. However, it remains unclear if there is an association between A>I(G) RNA-edited sites and sensitivity to genotoxic drugs. To address this issue, we employed a stringent bioinformatics approach to identify differentially RNA-edited sites (DESs) associated with low or high sensitivity (FDR 0.1, log2 fold change 2.5) according to the IC50 of PARP inhibitors, anthracyclines, and alkylating agents using WGS/RNA-seq data in BC cell lines. We then validated these findings in patients with basal subtype BC. These DESs are mainly located in non-coding regions, but a lesser proportion in coding regions showed predicted deleterious consequences. Notably, some of these DESs are previously reported as oncogenic variants, and in genes related to DNA damage repair, drug metabolism, gene regulation, the cell cycle, and immune response. In patients with BC, we uncovered DESs predominantly in immune response genes, and a subset with a significant association (log-rank test p < 0.05) between RNA editing level in LSR, SMPDL3B, HTRA4, and LL22NC03-80A10.6 genes, and progression-free survival. Our findings provide a landscape of RNA-edited sites that may be involved in drug response mechanisms, highlighting the value of A>I(G) RNA editing in clinical outcomes for BC.
Challenges for gene therapy in the financial sustainability of health systems: a scoping review
(2024) Ossandon, Hugo; Armijo, Nicolás; Vargas, Constanza; Repetto, Gabriela; Espinoza, Manuel
Aim: To review the available evidence about the strategies implemented or proposed for coverage or reimbursement for currently approved gene therapies. Methods: A scoping review was conducted to analyze the evidence published during the years 2016 to 2023. The main search criteria were coverage or reimbursement of gene therapy by healthcare systems. The eligible articles were those that described or proposed a financing model used to provide coverage in the various systems around the world. Results: The study identified 279 publications, and after removing duplicates and screening for eligibility, 10 were included in the study. The results show that various financing models have been proposed, including subscription-based payment models, outcome-based payment models, and amortization strategies. However, several barriers to implementing these models were identified, such as deficiencies in informatics systems for data collection, changes in laws or regulations, the lack of accessible clinical endpoints and administrative costs. Conclusion: This scoping review provides an overview of financing strategies for gene therapies. Gene therapies can cure rare or previously intractable diseases, but their high cost can make access difficult. Publishing experiences with these models can help evaluate their use and gather more evidence for their effectiveness.
Aloe vera peel-derived nanovesicles display anti-inflammatory properties and prevent myofibroblast differentiation
(2024) Ramírez, Orlando; Pomareda, Florencia; Olivares, Belén; Huang, Ya-Lin; Zavala, Gabriela; Carrasco, Javiera; Álvarez, Simón; Leiva, Camila; Hidalgo, Valeria; Romo, Pablo; Sánchez, Matías; Vargas, Ayleen; Martínez, Jessica; Aguayo, Sebastian; Schuh, Christina
Background: Aloe vera (AV) is a medicinal plant, most known for its beneficial effects on a variety of skin conditions. Its known active compounds include carbohydrates and flavonoids such as quercetin and kaempferol, among others. In the past decade, plant nanovesicles (NVs) have gained considerable interest as interkingdom communicators, presenting an opportunity for clinical standardization of natural products. In this study, we aimed to assess the potential of AVpNVs for the treatment of burn wounds. Methods: AVpNVs were isolated and characterized regarding vesicle yield (nanoparticle tracking analysis) and structure (transmission electron microscopy and atomic force microscopy), as well as their protein content with proteomics. We assessed key characteristics for treating burn wounds in vitro, such as the anti-inflammatory potential in LPS-stimulated macrophages and keratinocytes, and the effect of AVpNVs on myofibroblast differentiation and contraction. Key findings: AVpNVs presented a homogenous NV population, vesicular shape, and NV-associated protein markers. AVpNVs significantly decreased the secretion of pro-inflammatory cytokines TNFα, IL-1β, and IL-6. Furthermore, AVpNVs inhibited myofibroblast differentiation and significantly decreased their contractile potential in collagen matrices. Observed effects were linked to proteins identified in the isolates through proteomics analysis. Conclusion: AVpNVs displayed characteristics as an inflammatory modulator, while simultaneously diminishing myofibroblast differentiation and contraction. Novel strategies for burn wound treatment seek to decrease scarring on a cellular and molecular level in the early stages of wound healing, which makes AVpNVs a promising candidate for future plant-vesicle-based treatments.
Pannexin-1 expression in tumor cells correlates with colon cancer progression and survival
(2024) Fierro, Aaron; Landskron, Glauben; Camhi, Ilan; Basterrechea, Benjamín; Parada, Daniela; Lobos-González, Lorena; Dubois, Karen; Araneda, Catalina; Romero, Camila; Domínguez, Antonia; Vásquez, Gonzalo; López, Francisco; Alvarez, Karin; González, Carlos; Hager, Carolina; Balboa, Elisa; Eugenin, Eliseo; Hermoso, Marcela; De la Fuente, Marjorie
Aims: 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 stage-dependent 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.
Borders and liminality in the right to health of migrants in transit: The case of Colchane in Chile and Necoclí in Colombia
(2024) Jaramillo Contreras, Andrea Carolina; Cabieses, Báltica; Knipper, Michael; Rocha Jiménez, Teresita
The absence of the right to health of migrants in transit has evolved into a significant global health concern, particularly in the border regions thus, this study aims to improve knowledge in this area by exploring the effects of the spatio-temporal liminal characteristics at borders in the achievement of the right to health of migrants in transit moving across two of the most transited and dangerous borders in Latin America: Colchane (Chile-Bolivia) and the Dari´en Gap (Colombia-Panamá). Through a qualitative descriptive multi-case study, we implemented 50 semi-structured interviews (n = 30 in Chile and n = 20 in the Dari´en/Necoclí) involving national, regional, and local stakeholders. The findings highlight that the fulfilment of the right to health of migrants in transit is hindered by liminal dynamics at the borders. These dynamics include closure of borders, (in)securities, uncer tainty and waiting, lack of economic resources, lack of protection to all, liminal politics, and humanitarian in terventions. These findings surface how the borders’ liminality exacerbates the segregation of migrants in transit by placing them in a temporospatial limbo that undermines their right to health. Our study concludes that not just the politics but also the everyday practices, relationships and social infrastructure at borders impedes the enjoyment of the right to health of distressed migrants in transit. The short-term humanitarian response; illicit dynamics at borders; migratory regulations; and border and cross-border political structures are some of the most significant determinants of health at these borderlands.
Editorial: SLC6A1: the past, present and future
(2023) Johannesen, Katrine M.; Pérez Palma, Eduardo; Rubboli, Guido
Controlled Release of the Anticancer Drug Cyclophosphamide from a Superparamagnetic β‑Cyclodextrin Nanosponge by Local Hyperthermia Generated by an Alternating Magnetic Field
(2024) SALAZAR SANDOVAL, SEBASTIAN ANDRES; Díaz-Saldívar, Patricia; Araya, Ingrid; Celis, Freddy; Cortés-Arriagada, Diego; Riveros, Ana; Rojas-Romo, Carlos; Jullian, Carolina; Silva, Nataly; Yutronic, Nicolás; Kogan, Marcelo J.; Jara, Paul
β-cyclodextrin (β-CD) nanosponge (NS) was synthesized using diphenyl carbonate (DPC) as a cross-linker to encapsulate the antitumor drug cyclophosphamide (CYC), thus obtaining the NSs-CYC system. The formulation was then associated with magnetite nanoparticles (MNPs) to develop the MNPs-NSs-CYC ternary system. The formulations mentioned above were characterized to confirm the deposition of the MNPs onto the organic matrix and that the superparamagnetic nature of the MNPs was preserved upon association. The association of the MNPs with the NSs-drug complex was confirmed through field emission scanning electron microscopy, energy dispersive spectroscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, dynamic light scattering, ζ-potential, atomic absorption spectroscopy, X-ray powder diffraction, selected area electron diffraction, and vibrating-sample magnetometer. The superparamagnetic properties of the ternary system allowed the release of CYC by utilizing magnetic hyperthermia upon the exposure of an alternating magnetic field (AMF). The drug release experiments were carried out at different frequencies and intensities of the magnetic field, complying with the “Atkinson−Brezovich criterion”. The assays in AMF showed the feasibility of release by controlling hyperthermia of the drug, finding that the most efficient conditions were F = 280 kHz, H = 15 mT, and a concentration of MNPs of 5 mg/mL. CYC release was temperature-dependent, facilitated by local heat generation through magnetic hyperthermia. This phenomenon was confirmed by DFT calculations. Furthermore, the ternary systems outperformed the formulations without MNPs regarding the amount of released drug. The MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assays demonstrated that including CYC within the magnetic NS cavities reduced the effects on mitochondrial activity compared to those observed with the free drug. Finally, the magnetic hyperthermia assays showed that the tertiary system allows the generation of apoptosis in HeLa cells, demonstrating that the MNPs embedded maintain their properties to generate hyperthermia. These results suggest that using NSs associated with MNPs could be a potential tool for a controlled drug delivery in tumor therapy since the materials are efficient and potentially nontoxic.
High-resolution manometry thresholds and motor patterns among asymptomatic individuals.
(2022) Rengarajan, Arvind; Rogers, Benjamin D.; Wong, Zhiqin; Tolone, Salvatore; Sifrim, Daniel; Serra, Jordi; Savarino, Edoardo; Roman, Sabine; Remes-Troche, Jose M.; Ramos, Rosa; Perez de la Serna, Julio; Pauwels, Ans; Leguizamo, Ana Maria; Yeh Lee, Yeong; Kawamura, Osamu; Hayat, Jamal; Hani, Albis; Gonlachanvit, Sutep; Cisternas, Daniel; Cisternas, Daniel; Carlson, Dustin; Bor, Serhat; Bhatia, Shobna; Abrahao, Luiz; Pandolfino, John; Gyawali, C. Prakash
Objective: High-resolution manometry (HRM) is the current standard for characterization of esophageal body and esophagogastric junction (EGJ) function. We aimed to examine the prevalence of abnormal esophageal motor patterns in health, and to determine optimal thresholds for software metrics across HRM systems. Design: Manometry studies from asymptomatic adults were solicited from motility centers worldwide, and were manually analyzed using integrated relaxation pressure (IRP), distal latency (DL), and distal contractile integral (DCI) in standardized fashion. Normative thresholds were assessed using fifth and/or 95th percentile values. Chicago Classification v3.0 criteria were applied to determine motor patterns across HRM systems, study positions (upright vs supine), ages, and genders. Results: Of 469 unique HRM studies (median age 28.0, range 18-79 years). 74.6% had a normal HRM pattern; none had achalasia. Ineffective esophageal motility (IEM) was the most frequent motor pattern identified (15.1% overall), followed by EGJ outflow obstruction (5.3%). Proportions with IEM were lower using stringent criteria (10.0%), especially in supine studies (7.1%-8.5%). Other motor patterns were rare (0.2%-4.1% overall) and did not vary by age or gender. DL thresholds were close to current norms across HRM systems, while IRP thresholds varied by HRM system and study position. Both fifth and 95th percentile DCI values were lower than current thresholds, both in upright and supine positions. Conclusions: Motor abnormalities are infrequent in healthy individuals and consist mainly of IEM, proportions of which are lower when using stringent criteria in the supine position. Thresholds for HRM metrics vary by HRM system and study position.
Reactivation of adult-onset Still's disease after use of the COVID-19 ChAdOx1-S vaccine
(2022) Ibáñez, Sebastián; Morales Murillo, Luis; Rivera Vergara, Matías de la; Saldías Martínez, Roberto
A woman in her 60s with a history of adult-onset Still's disease (AOSD) in remission for 14 years received the ChAdOx1-S vaccine as a booster to her initial vaccination schedule (two doses of CoronaVac vaccine 6 months apart). Two weeks later, she consulted for symptoms suggestive of AOSD reactivation. This was confirmed during hospitalisation, where renal and cardiac involvement were also observed. Despite using high-dose corticosteroids, troponin T and N-terminal pro hormone B-type natriuretic peptide (NT-proBNP) were persistently elevated. Tocilizumab was used, with which the patient achieved complete remission of her symptoms and normalised her laboratory tests.
Características de los docentes clínicos cirujano-dentistas más valorados por la comunidad odontológica
(2022) Moreno, Yasna; Frey Moreno, Catalina Belén; Frey, Maximiliano
Faced with the complex scenario in dental clinical care, the following question arises: Does the valued clinical professor have a defined profile? The search for an ideal clinical teacher for the purpose of achieving competencies in their students is usually a difficult task. The objective of this study is to determine the characteristics of clinical teachers considered experts according to the appreciation of the odontological community.
Abordaje transoral para la extracción de un diente supernumerario intranasal. Presentación de un caso y revisión de la literatura
(2022) Figueroa C., Liberto; Smith ruiz, Ronald harold; Daza, J.; Polanco, A.; Andraca, F.
El diente supernumerario de ubicación nasal es una patología de baja prevalencia en la población con diferentes formas y sintomatología clínica. Es importante establecer un diagnóstico respecto a sus características clínicas y radiológicas para realizar una planificación de tratamiento quirúrgica adecuada, con nula o escasas complicaciones post intervención. Presentación del caso: En el presente estudio se reporta el caso de un niño de 10 años de edad, sin antecedentes mórbidos, que recurre al servicio por presentar un diente supernumerario en la línea media hallado radiográficamente. El CBCT demuestra un mesiodens en el septum nasal, palatal inclinado e invertido, parcialmente erupcionado cubierto por mucosa nasal, con su corona en sentido a la cavidad nasal en relación a las fosas nasales. El diente fue extraído con anestesia general mediante un abordaje transoral a través de una vestibulotomía. El diente supernumerario nasal es una patología poco prevalente. Es importante conocer sus características clínicas y radiográficas ya que determinarán el tipo de abordaje a realizar. El grado de erupción, la distancia a la espina nasal anterior y su sintomatología asociada son fundamentales para determinar si el abordaje quirúrgico es intraoral o extraoral
Características clínicas y resultados de pacientes con fibrosis quística con enfermedad pulmonar avanzada: experiencia en 10 años del Instituto Nacional del Tórax
(2022) Gutiérrez M., José; Pinochet F., Víctor; Irazoqui G., Paula; Benavides G., Guacolda; Andrade H., Christian; Orellana, María; Melo T., Joel
Advanced cystic fibrosis lung disease (ACFLD) is the leading cause of morbidity and mortality in patients with Cystic Fibrosis (CF). Objective: to describe clinical characteristics of patients with CF with ACFLD and mortality during follow-up. Method: Descriptive, retrospective study of patients with CF and ACFLD: FEV1 ≤ 40%, oxygen dependent, and/or referred to a lung transplant program. Clinical, microbiological, functional, genetic and mortality characteristics were collected. Results: Of 111 controlled patients, 39% met criteria for ACFLD. 52% were men and the mean age was 29,8 yearsold. The average BMI was 19.9 kg/m2, 72% had pancreatic insufficiency and 87% had a genetic study, being the DF508 mutation the most frequent (67%). The average age of diagnosis was 11.2 years (SD ± 13 years), being in 54,5% over the age of 4 years. 75% had chronic Pseudomonas infection. 68% were oxygen dependent and 18% on noninvasive mechanical ventilation. In the last year of follow-up 70% had 2 or more hospitalizations. Of 27 patients who have been referred for transplantation, 7 underwent lung transplantation, 3 died waiting on the transplant list, 9 had contraindications: 4 due to malnutrition and 5 to poor adherence and poor support network. 32% (n = 14) of the ACFLD patients died, 93% due to respiratory causes. Conclusion: 39% of the patients had ACFLD. The average age for CF diagnosis was 11.2 years (SD ± 13 years) Barriers to entering the transplant list are: malnutrition, poor adherence, and lack of a support network. This is a population with a high mortality.
Patrones de conducta alimentaria y estado nutricional en estudiantes universitarios tras dos años de educación en línea
(2022) Fuentes Barría, Héctor; Aguilera Eguía, Raúl; González-Wong, Catalina
Fundamento: La población estudiantil universitaria es particularmente vulnerable a adquirir estilos de conducta alimentaria poco saludables producto de factores como la inadecuada nutrición y el elevado sedentarismo generado por causa de la elevada carga académica y poco tiempo libre, cuyo resultado conlleva potenciales riesgos para la salud. Objetivo: Describir y comparar el patrón de conducta alimentaria y estado nutricional en estudiantes de sexto año de la carrera de Odontología impartida por la Universidad Andrés Bello, sede Concepción luego de dos años de educación online por COVID-19. Métodos: Estudio observacional, descriptivo de corte transversal. La muestra se conformó por 18 estudiantes universitarios con un promedio de edad de 24,94 ± 1,95 años clasificados como eutróficos (21,92 ± 1,27 km/m2) y con sobrepeso (28,13 ± 1,53 km/m2), presentando ambos grupos hábitos alimentarios suficientes (12,27 ±1,43 puntos). Se aplicó la Encuesta de Conductas y Hábitos Alimentarios en Educación Superior y se realizó una comparación entre grupos según estado nutricional determinado por el Índice de Masa Corporal. Resultados: Solo se observó diferencias medias significativas entre grupos para la preocupación alimentaria (p= 0,009). Conclusión: La preocupación alimentaria sugiere un interés por el autocuidado. Se requieren otros estudios que expliquen todas las variables moduladoras de la conducta alimentaria con el objetivo de promover espacios universitarios que conlleven la concientización de estilos de vida saludables luego de dos años de educación superior online producto de la pandemia COVID-19.
Characteristics of Medically Transported Critically Ill Children with Respiratory Failure in Latin America: Implications for Outcomes
(2021) Serra, Jesus; Díaz, Franco; Cruces, Pablo; Carvajal, Cristobal; Nuñez, Maria; Donoso, A.; Bravo, J A; Carbonell, M.; Courtie, C.; Fernández. A.; Martínez, L.; Martínez, J.; Menta, S.; Pedrozo, Luis; Wegner, A.; Monteverde, Nicolas; Jaramillo, Juan; Jabornisky, Roberto; González, Sebastián; Kudchadkar, Sapna; Vásquez, Pablo; On behalf of LARed Network
Several challenges exist for referral and transport of critically ill children in resource-limited regions such as Latin America; however, little is known about factors associated with clinical outcomes. Thus, we aimed to describe the characteristics of critically ill children in Latin America transferred to pediatric intensive care units for acute respiratory failure to identify risk factors for mortality. We analyzed data from 2,692 patients admitted to 28 centers in the Pediatric Collaborative Network of Latin America Acute Respiratory Failure Registry. Among patients referred from another facility (773, 28%), nonurban transports were independently associated with mortality (adjusted odds ratio = 9.4; 95% confidence interval: 2.4-36.3).
Pembrolizumab in Combination with Neoadjuvant Chemoradiotherapy for Patients with Resectable Adenocarcinoma of the Gastroesophageal Junction
(2022) Zhu, Mojun; Chen, Chunhua; Foster, Nathan; Hartley, Christopher; Mounajjed, Taofic; Salomao, Marcela; Fruth, Briant; Beamer, Staci; Kim, Yohan; Harrington, Susan; Pitot, Henry; Sanhueza, Cristobal; Feng, Yening; Herrmann, Joerg; McWilliams, Robert; Lucien, Fabrice; Huang, Bing; Wee, Wen; Bekaii, Tanios; Dong, Haidong; Wigle, Dennis; Ahn, Daniel; Hallemeier, Chris; Blackmon, Shanda; Yoon, Harry
Purpose: This phase Ib/2 trial investigated pembrolizumab-containing trimodality therapy in patients with gastroesophageal junction (GEJ) adenocarcinoma. Patients and methods: Patients with GEJ adenocarcinoma (cT1-3NanyM0) received neoadjuvant pembrolizumab-containing chemoradiation (CROSS regimen) followed by surgical resection and adjuvant pembrolizumab. The primary endpoints were tolerability in the first 16 patients and pathologic complete response [pCR (ypT0N0)]. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). An independent propensity-score-matched cohort (treated with CROSS without immunotherapy) was used for comparison. Exploratory analyses included immune biomarkers in the tumor microenvironment (TME) and plasma. Results: We enrolled 31 eligible patients, of whom 29 received all expected doses of neoadjuvant pembrolizumab and 28 underwent R0 resection. Safety endpoints were met. The primary efficacy endpoint was not met [7/31 (22.6%) achieved pCR]. Patients with high [i.e., combined positive score (CPS) ≥ 10] baseline expression of programmed death (PD)-L1 in the TME had a significantly higher pCR rate than those with low expression [50.0% (4/8) vs. 13.6% (3/22); P = 0.046]. Patients with high PD-L1 expression also experienced longer PFS and OS than propensity-score-matched patients. Among trial patients with PD-L1 CPS < 10, unprespecified analysis explored whether extracellular vesicles (EV) could identify further responders: an elevated plasma level of PD-L1-expressing EVs was significantly associated with higher pCR. Conclusions: Adding pembrolizumab to trimodality therapy showed acceptable tolerability but did not meet the pre-specified pCR endpoint. Exploratory analyses suggested that high PD-L1 expression in the TME and/or on EVs may identify patients most likely to achieve tumor response.
Associations of Early Systolic Blood Pressure Control and Outcome After Thrombolysis- Eligible Acute Ischemic Stroke: Results From the ENCHANTED Study
(2022) Wang, Xia; Minhas, Jatinder S.; Moullaali, Tom J.; Di Tanna, Gian Luca; Lindley, Richard I.; Chen, Xiaoying; Arima, Hisatomi; Chen, Guofang; Delcourt, Candice; Bath, Philip M.; Broderick, Joseph P.; Demchuk, Andrew M.; Donnan, Geoffrey A.; Durham, Alice C.; Lavados, Pablo; Lee, Tsong-Hai; Levi, Christopher; Martins, Sheila O.; Olavarría, Verónica V.; Pandian, Jeyaraj D.; Parsons, Mark W.; Pontes-Neto, Octavio M.; Ricci, Stefano; Sato, Shoichiro; Sharma, Vijay K.; Silva, Federico; Thang, Nguyen H.; Wang, Ji-Guang; Woodward, Mark; Chalmers, John; Song, Lili; Anderson, Craig S.; Robinson, Thompson G.
BACKGROUND AND PURPOSE: In thrombolysis-eligible patients with acute ischemic stroke, there is uncertainty over the most appropriate systolic blood pressure (SBP) lowering profile that provides an optimal balance of potential benefit (functional recovery) and harm (intracranial hemorrhage). We aimed to determine relationships of SBP parameters and outcomes in thrombolyzed acute ischemic stroke patients. METHODS: Post hoc analyzes of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study), a partial-factorial trial of thrombolysis-eligible and treated acute ischemic stroke patients with high SBP (150–180 mm Hg) assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) alteplase and intensive (target SBP, 130–140 mm Hg) or guideline-recommended (target SBP <180 mm Hg) treatment. All patients were followed up for functional status and serious adverse events to 90 days. Logistic regression models were used to analyze 3 SBP summary measures postrandomization: attained (mean), variability (SD) in 1–24 hours, and magnitude of reduction in 1 hour. The primary outcome was a favorable shift on the modified Rankin Scale. The key safety outcome was any intracranial hemorrhage. RESULTS: Among 4511 included participants (mean age 67 years, 38% female, 65% Asian) lower attained SBP and smaller SBP variability were associated with favorable shift on the modified Rankin Scale (per 10 mm Hg increase: odds ratio, 0.76 [95% CI, 0.71–0.82]; P<0.001 and 0.86 [95% CI, 0.76–0.98]; P=0.025) respectively, but not for magnitude of SBP reduction (0.98, [0.93– 1.04]; P=0.564). Odds of intracranial hemorrhage was associated with higher attained SBP and greater SBP variability (1.18 [1.06–1.31]; P=0.002 and 1.34 [1.11–1.62]; P=0.002) but not with magnitude of SBP reduction (1.05 [0.98–1.14]; P=0.184). CONCLUSIONS: Attaining early and consistent low levels in SBP <140 mm Hg, even as low as 110 to 120 mm Hg, over 24 hours is associated with better outcomes in thrombolyzed acute ischemic stroke patients.
Proposal of minimum elements for screening and diagnosis of gastric cancer by an international Delphi consensus
(2022) Kakushima, Naomi; Fujishiro, Mitsuhiro; Chan, Shannon Melissa; Cortas, George Adel; Dinis-Ribeiro, Mario; González, Robinson; Kodashima, Shinya; Lee, Sun-Young; Linghu, Enqiang; Mabe, Katsuhiro; Pan, Wensheng; Parra-Blanco, Adolfo; Pioche, Mathieu; Rollan, Antonio; Sumiyama, Kazuki; Tanimoto, Miguel; World Endoscopy Organization Stomach and Duodenal Diseases Committee
The World Endoscopy Organization Stomach and Duodenal Diseases Committee extracted minimum elements for screening and diagnosis of gastric cancer (GC) in aim to support countries that do not have national guidelines on screening and diagnosis of GC. Current national or international guidelines were collected worldwide and recommendations were classified according to the quality of evidence and were finalized through a modified Delphi method. The minimum elements consist of seven categories: [1] Extraction of high-risk patients of GC before esophagogastroduodenoscopy (EGD), [2] Patients who need surveillance of GC, [3] Method to ensure quality of EGD for detection of GC, [4] Individual GC risk assessment by EGD, [5] Extraction of high-risk patients of GC after EGD [6] Qualitative or differential diagnosis of GC by EGD, and [7] Endoscopic assessment to choose the therapeutic strategy for GC. These minimum elements will be a guide to promote the elimination of GC among countries with a high incidence of GC who lack national guidelines or screening programs.
Barriers and Facilitators in Access to Diabetes, Hypertension, and Dyslipidemia Medicines: A Scoping Review
(2022) Castillo-Laborde, Carla; Hirmas Adauy, Macarena; Matute, María Isabel; Jasmen, Anita; Urrejola, Oscar; Molina, Xaviera; Awad, Camila; Frey, Catalina; Pumarino, Sofia; Descalzi, Fernando; Ruiz, Tomás; Plass, Barbara
Objective: Identify barriers and facilitators in access to medicines for diabetes, hypertension, and dyslipidemia, considering patient, health provider, and health system perspectives. Methods: Scoping review based on Joanna Briggs methodology. The search considered PubMed, Cochrane Library, CINAHL, Academic Search Ultimate, Web of Science, SciELO Citation Index, and grey literature. Two researchers conducted screening and eligibility phases. Data were thematically analyzed. Results: The review included 219 documents. Diabetes was the most studied condition; most of the evidence comes from patients and the United States. Affordability and availability of medicines were the most reported dimension and specific barrier respectively, both cross-cutting concerns. Among high- and middle-income countries, identified barriers were cost of medicines, accompaniment by professionals, long distances to facilities, and cultural aspects; cost of transportation emerges in low-income settings. Facilitators reported were financial accessibility, trained health workers, medicines closer to communities, and patients' education. Conclusion: Barriers and facilitators are determined by socioeconomic and cultural conditions, highlighting the role of health systems in regulatory and policy context (assuring financial coverage and free medicines); providers' role bringing medicines closer; and patients' health education and disease management.
Anterior Cruciate Ligament Rupture in Skeletally Immature Patients
(2022) Cancino, Benjamín; Muñoz, Carlos; Tuca, Maria; Birrer, Estefanía; Sepúlveda, Matías
In the past 20 years, sports injuries in pediatric and adolescent athletes have increased dramatically, with anterior cruciate ligament (ACL) injuries accounting for more than 25% of all knee injuries at this age. Diagnosis is based on detailed clinical history, physical examination, and imaging assessment, where magnetic resonance imaging plays a central role. The growing immature skeleton presents specific characteristics, which require unique methods for surgical reconstruction, ideally avoiding the physes or minimizing the risk of damaging them. Specific rehabilitation protocols are needed, and these patients face a higher risk of recurrent and contralateral ACL injury. Nonsurgical treatment or delayed reconstruction has been associated with persistent instability, activity modifications, worst functional outcomes, and increased risk of irreparable injuries to menisci and articular cartilage. Consequently, surgical stabilization is the preferred treatment for most patients, despite the eventual risk of angular deformities or limb-length discrepancies due to iatrogenic physeal injury. A variety of surgical techniques have been described, depending on the skeletal maturity and growth remaining. Targeted prevention programs play a key role in reducing the risk of ACL injury, are easy to implement, and require no additional equipment. High-quality evidence supports its use in all pediatric athletes.

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