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Fibroblast Growth Factor Receptors (FGFRs) play a significant role in Estrogen Receptor-positive (ER+) breast cancer by contributing to tumorigenesis and endocrine resistance. This review explores the structure, signaling pathways, and implications of FGFRs, particularly FGFR1, FGFR2, FGFR3, and FGFR4, in ER+ breast cancer. FGFR1 is frequently amplified, especially in aggressive Luminal B-like tumors, and its amplification is associated with poor prognosis and treatment resistance. The co-amplification of FGFR1 with oncogenes like EIF4EBP1 and NSD3 complicates its role as a standalone oncogenic driver. FGFR2 amplification, though less common, is critical in hormone receptor regulation, driving proliferation and treatment resistance. FGFR3 and FGFR4 also contribute to endocrine resistance through various mechanisms, including the activation of alternate signaling pathways like PI3K/AKT/mTOR and RAS/RAF/MEK/ERK. Endocrine resistance remains a major clinical challenge, with around 70% of breast cancers initially hormone receptor positive. Despite the success of CDK 4/6 inhibitors in combination with endocrine therapy (ET), resistance often develops, necessitating new treatment strategies. FGFR inhibitors have shown potential in preclinical studies, but clinical trials have yielded limited success due to off-target toxicities and lack of predictive biomarkers. Current clinical trials, including those evaluating FGFR inhibitors like erdafitinib, lucitanib, and dovitinib, have demonstrated mixed outcomes, underscoring the complexity of FGFR signaling in breast cancer. The interplay between FGFR and other signaling pathways highlights the need for comprehensive molecular profiling and personalized treatment approaches. Future research should focus on identifying robust biomarkers and developing combination therapies to enhance the efficacy of FGFR-targeted treatments. In conclusion, targeting FGFR signaling in ER+ breast cancer presents both challenges and opportunities. A deeper understanding of the molecular mechanisms and resistance pathways is crucial for the successful integration of FGFR inhibitors into clinical practice, aiming to improve outcomes for patients with endocrine-resistant breast cancer.

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The MET gene, known as MET proto-oncogene receptor tyrosine kinase, was first identified to induce tumor cell migration, invasion, and proliferation/survival through canonical RAS-CDC42-PAK-Rho kinase, RAS-MAPK, PI3K-AKT-mTOR, and ß-catenin signaling pathways, and its driver mutations, such as MET gene amplification (METamp) and the exon 14 skipping alterations (METex14), activate cell transformation, cancer progression, and worse patient prognosis, principally in lung cancer through the overactivation of their own oncogenic and MET parallel signaling pathways. Because of this, MET driver alterations have become of interest in lung adenocarcinomas since the FDA approval of target therapies for METamp and METex14 in 2020. However, after using MET target therapies, tumor cells develop adaptative changes, favoring tumor resistance to drugs, the main current challenge to precision medicine. Here, we review a link between the resistance mechanism and MET signaling pathways, which is not only limited to MET. The resistance impacts MET parallel tyrosine kinase receptors and signals shared hubs. Therefore, this information could be relevant in the patient's mutational profile evaluation before the first target therapy prescription and follow-up to reduce the risk of drug resistance. However, to develop a resistance mechanism to a MET inhibitor, patients must have access to the drugs. For instance, none of the FDA approved MET inhibitors are registered as such in Chile and other developing countries. Constant cross-feeding between basic and clinical research will thus be required to meet future challenges imposed by the acquired resistance to targeted therapies.

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BACKGROUND: The incorporation of novel drugs, such as proteasome inhibitors and immunomodulators, improved considerably the survival of patients with multiple myeloma. AIM: To evaluate the effect on survival of proteasome inhibitors and immunomodulators in patients with multiple myeloma in two national hospitals. MATERIAL AND METHODS: Review of clinical records from two hospitals of Santiago. Epidemiological, clinical, laboratory and therapeutic data was obtained from 144 patients with multiple myeloma diagnosed between 2002 and 2016. RESULTS: Information was retrieved from 78 patients at one center and from 66 at the other center. The mean age at diagnosis was 58 and 62 years, the proportion of males was 53% and 52%, and presentation at stage III was 34% and 46%, respectively. The use of novel drugs, mainly bortezomib, was 90% in one of the centers and 3% in the other one. The use of autologous stem-cell transplantation was 47% and 3% respectively. The median overall survival of patients from the centers with and without access to novel drugs was 117 and 71 months respectively (p < 0.05). The five-year overall survival was 93 and 43% respectively (p < 0.05). CONCLUSIONS: The use of novel drugs, especially bortezomib, and autologous stem-cell transplantation significantly improved the survival of multiple myeloma patients treated in national hospitals. It is necessary to include them as a first line treatment.

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BACKGROUND: The incorporation of novel drugs, such as proteasome inhibitors and immunomodulators, improved considerably the survival of patients with multiple myeloma. Aim: To evaluate the effect on survival of proteasome inhibitors and immunomodulators in patients with multiple myeloma in two national hospitals. MATERIAL AND METHODS: Review of clinical records from two hospitals of Santiago. Epidemiological, clinical, laboratory and therapeutic data was obtained from 144 patients with multiple myeloma diagnosed between 2002 and 2016. Results: Information was retrieved from 78 patients at one center and from 66 at the other center. The mean age at diagnosis was 58 and 62 years, the proportion of males was 53% and 52%, and presentation at stage III was 34% and 46%, respectively. The use of novel drugs, mainly bortezomib, was 90% in one of the centers and 3% in the other one. The use of autologous stem-cell transplantation was 47% and 3% respectively. The median overall survival of patients from the centers with and without access to novel drugs was 117 and 71 months respectively (p < 0.05). The five-year overall survival was 93 and 43% respectively (p < 0.05). CONCLUSIONS: The use of novel drugs, especially bortezomib, and autologous stem-cell transplantation significantly improved the survival of multiple myeloma patients treated in national hospitals. It is necessary to include them as a first line treatment.

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The adequate handling of central venous catheters is a key element in the management of patients with cancer. Catheter-associated deep vein thrombosis is frequently observed in patients with malignant diseases; however, despite being a common complication among these patients, objective information concerning its epidemiology, clinical course, prophylaxis and treatment strategies is very limited. The reported incidence of catheter-related thrombosis (CRT) is highly variable, depending on symptomatic events, or if patients are screened for asymptomatic thrombosis. Several factors have been identified as potential predisposing factors for CRT, both technical and pathological aspects. The anticoagulant of choice is still unclear; while low-molecular-weight heparin is most commonly used, recent studies assessing the role of direct oral anticoagulants in the treatment of CRT show promise as an alternative, but the evidence remains insufficient and the decision must be made on a case-by-case basis.

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Cytoreductive nephrectomy has been an integral part of management in metastatic renal cell carcinoma for patients with good performance status, based on the benefit shown by prospective trials in the interferon era and retrospective trials in the targeted therapies era. Clinical Trial to Assess the Importance of Nephrectomy (CARMENA), the first prospective phase III trial comparing a targeted agent alone (sunitinib) versus nephrectomy plus sunitinib, has been recently published, showing non-inferiority for the nephrectomy-sparing arm. In this article, we discuss the impact of nephrectomy including its immune-mediated effects, surgical morbidity and mortality, and the clinical data supporting the indications of nephrectomy in order to analyze the CARMENA trial in context, with the aim to identify optimal strategies for different patient populations in the metastatic setting.

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OBJECTIVE: Advanced age is an independent predictor of postoperative atrial fibrillation (POAF) in patients undergoing coronary artery bypass surgery. We evaluated whether left atrial (LA) dysfunction assessed by strain contributes to identifying elderly patients prone to POAF. METHODS: Case-control study of 70 subjects undergoing coronary artery bypass surgery. Clinical and laboratory characteristics were recorded at baseline and 72 hours after surgery. Echocardiography was performed during the preoperative period; LA dimensions and deformation by strain (systolic wave [LASs]) as well as strain rate (systolic wave [LASRs] and atrial contraction wave [LASRa]) were assessed. RESULTS: Postoperative atrial fibrillation occurred in 38.5% of patients within the first 72 hours after surgery (28.5% of the younger vs. 48.6% of the older group). Baseline and postoperative inflammatory markers as well as total surgical and aortic clamp time were similar between groups. LA function was markedly impaired in subjects with POAF. Age correlated with LASs, LASRs, and LASRa. These associations remained consistent when subjects 75 years or older were considered separately. Both LASs and LASRa for patients with or without POAF, respectively, were significantly impaired in elderly subjects with POAF. Multivariate analysis provided further evidence that both LASs and age are independent predictors for POAF. CONCLUSION: Age-related changes in atrial function preceding atrial dilation are evident only upon LA strain analysis. LA strain impairment is an independent predictor of POAF irrespective of age and may serve as a surrogate marker for biological processes involved in establishing the substrate for POAF.

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Recent findings have shown that photosynthesis in the skin of the seed of Posidonia oceanica enhances seedling growth. The seagrass genus Posidonia is found only in two distant parts of the world, the Mediterranean Sea and southern Australia. This fact led us to question whether the acquisition of this novel mechanism in the evolution of this seagrass was a pre-adaptation prior to geological isolation of the Mediterranean from Tethys Sea in the Eocene. Photosynthetic activity in seeds of Australian species of Posidonia is still unknown. This study shows oxygen production and respiration rates, and maximum PSII photochemical efficiency (Fv : Fm) in seeds of two Australian Posidonia species (P. australis and P. sinuosa), and compares these with previous results for P. oceanica. Results showed relatively high oxygen production and respiratory rates in all three species but with significant differences among them, suggesting the existence of an adaptive mechanism to compensate for the relatively high oxygen demands of the seeds. In all cases maximal photochemical efficiency of photosystem II rates reached similar values. The existence of photosynthetic activity in the seeds of all three species implicates that it was an ability probably acquired from a common ancestor during the Late Eocene, when this adaptive strategy could have helped Posidonia species to survive in nutrient-poor temperate seas. This study sheds new light on some aspects of the evolution of marine plants and represents an important contribution to global knowledge of the paleogeographic patterns of seagrass distribution.

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Therapeutic hypothermia, recently termed target temperature management (TTM), is the cornerstone of neuroprotective strategy. Dating to the pioneer works of Fay, nearly 75 years of basic and clinical evidence support its therapeutic value. Although hypothermia decreases the metabolic rate to restore the supply and demand of O2, it has other tissue-specific effects, such as decreasing excitotoxicity, limiting inflammation, preventing ATP depletion, reducing free radical production and also intracellular calcium overload to avoid apoptosis. Currently, mild hypothermia (33°C) has become a standard in post-resuscitative care and perinatal asphyxia. However, evidence indicates that hypothermia could be useful in neurologic injuries, such as stroke, subarachnoid hemorrhage and traumatic brain injury. In this review, we discuss the basic and clinical evidence supporting the use of TTM in critical care for acute brain injury that extends beyond care after cardiac arrest, such as for ischemic and hemorrhagic strokes, subarachnoid hemorrhage, and traumatic brain injury. We review the historical perspectives of TTM, provide an overview of the techniques and protocols and the pathophysiologic consequences of hypothermia. In addition, we include our experience of managing patients with acute brain injuries treated using endovascular hypothermia.

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Introducción: Los pacientes con válvulas mecánicas cardíacas (VMC) representan una proporción significativa del total de pacientes que requieren anticoagulación. Sin embargo, hay pocos estudios que comparen la efectividad de la anticoagulación con distintos antagonistas de vitamina K (AVK). Objetivo: Comparar la efectividad y seguridad del tratamiento con warfarina y acenocumarol en pacientes con VMC. Métodos: Estudio observacional de pacientes en po-liclínico de anticoagulación UC sometidos a recambio valvular entre los años 2005 y 2013. Se estandarizó las dosis de AVK con software Isaza Hytwin Biostac 2.0. Se evaluaron registros de hemorragia mayor y menor (seguridad) y accidentes vasculares y embolías sistémicas (efectividad). La efectividad se analizó mediante el tiempo en rango terapéutico (TTR) con método de Ro-sendaal. Resultados: Se incluyó 365 pacientes con edad promedio de 64,1 +/- 13,2 años, 53,9 por ciento de sexo femenino. El seguimiento promedio fue de 33,3 +/- 18 meses; La mortalidad registrada fue 2,1 por ciento. El promedio de TTR fue 68 +/- 13,3 por ciento (recambio aórtico TTR 66,1 +/- 12,6 por ciento, recambio mitral TTR 65,8 +/- 13,8 por ciento y recambio mitro-aórtico TTR 61,2 +/- 12 por ciento). Acenocumarol presentó un TTR menor que warfarina (65,1 +/- 13,1 vs. 71,2 +/- 13,6, p = 0,001), sin aumento del riesgo de complicaciones. Conclusión: Aunque warfarina ofrece un mejor perfil de TTR, no existen diferencias significativas en la eficacia o seguridad al compararla con acenocumarol.

Background: Patients with cardiac mechanical valves (MHV) represent a significant proportion of all patients requiring anticoagulation. However, there are few studies comparing safety and efficacy of different vitamin K antagonists (VKA). Aim: To compare the efficacy and safety of warfarin and acenocoumarol in patients with MHV. Methods: Observational study of patients who had a mitral and /or aortic valve replacement between 2005 and 2013, followed at the Catholic University anticoagulation clinics. VKA dose adjustments were performed using the Isaza Hytwin Biostac 2.0 software. Major and minor bleeding (safety) and stroke and systemic embolism (effectiveness) were evaluated. The efficacy was estimated by the time in therapeutic range (TTR) with the Rosendaal method. Results: 365 patients were included with a mean age of 64.1 +/- 13.2 years, 53.9 percent of them were females. Mean follow-up was 33.3 +/- 18 months Overall mortality rate was 2.1 percent, which is similar to that of patients treated with VKA for other reasons. The average TTR was 68 +/- 13.3 percent (66,1 +/- 12,6 percent for aortic valves, 65,8 +/- 13,8 percent for mitral valves and 61,2 +/- 12 percent for aortic and mitral valves). TTR was lower with acenocoumarol compared to warfarin (65.1 +/- 13.1 vs. 71.2 +/- 13.6 , p = 0.001 ), However, the risk of complications was not different between groups. Conclusions: Although warfarin provides a better profile of TTR , there were no significant differences in efficacy or safety when compared with acenocoumarol.

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Infective endocarditis caused by Listeria monocytogenesis an extremely rare but usually aggressive disease. We have seen in recent years an increase in age of onset of this disease and a predilection for patients with valvular disease, especially prosthetic valve. The treatment of choice is ampicillin, which is combined with gentamicin for synergy. It is known that even with treatment the mortality is very high and higher than in other types of bacterial endocarditis. With optimal therapy, that is medical-surgical, mortality has declined significantly in recent years. We presents a review of the literature and a clinical case of a patient with a febrile syndrome diagnosed as a infective endocarditis caused by L. monocytogenestreated medically with successful outcome to date.

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We report a 40 year-old male presenting in the emergency room with headache, vertigo and left hemiparesis. A magnetic resonante imaging reported a left cerebellar infarction with occlusion of the basilar artery and a dissection of the right vertebral artery. The patient experienced a clinical deterioration with the appearance of a right hemiparesis. Therefore a brain angiography was performed along with a mechanical thrombolysis using a Solitaire FR® revascularization device. A thrombus located in the distal third of the artery was eliminated obtaining a complete perfusión of the artery. The patient had a satisfactory evolution.

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Infective endocarditis caused by Listeria monocytogenesis an extremely rare but usually aggressive disease. We have seen in recent years an increase in age of onset of this disease and a predilection for patients with valvular disease, especially prosthetic valve. The treatment of choice is ampicillin, which is combined with gentamicin for synergy. It is known that even with treatment the mortality is very high and higher than in other types of bacterial endocarditis. With optimal therapy, that is medical-surgical, mortality has declined significantly in recent years. We presents a review of the literature and a clinical case of a patient with a febrile syndrome diagnosed as a infective endocarditis caused by L. monocytogenestreated medically with successful outcome to date.

La endocarditis infecciosa por Listeria monocytogenes es una enfermedad extremadamente infrecuente, pero usualmente agresiva. Se ha observado en los últimos años un aumento en la edad de presentación y una predilección por pacientes con enfermedad valvular, especialmente válvula protésica. El tratamiento de elección es ampicilina combinada con un aminoglucósido para obtener sinergismo. Aun con un tratamiento adecuado, la mortalidad es elevada y mayor que en otros tipos de endocarditis bacteriana. Con una terapia óptima, incluyendo la resolución quirúrgica, la mortalidad ha disminuido significativamente en los últimos años. Se presenta una revisión de la literatura científica a partir de un caso clínico de un paciente con un síndrome febril en el que se diagnosticó una endocarditis por L. monocytogenesque fue tratada en forma médica con un resultado exitoso.

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We report a 40year-old male presenting in the emergeney room with headache, vértigo and left hemiparesis. A magnetic resonante imaging reporten a left cerebellar infarction with occlusion of the basilar artery ana dissection ofthe right vertebral artery. Thepatient experienced a clinical deterioration with the appearance ofa right hemiparesis. Therefore a brain angiography wasperformed alongwith a mechanical thrombolysis using a Solitaire FR® revascularization device. A thrombus located in the distal third ofthe artery was eliminated obtaining a complete perfusión ofthe artery. Thepatient had a satisfactory evolution.

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BACKGROUND: Carotid intima media thickness (CIMT) is a marker of cardiovascular damage that can be modified by traditional risk factors. AIM: To determine attributable risk factors for a high CIMT among healthy adults. MATERIAL AND METHODS: A sample of 1270 individuals (636 males and 634 females) aged 44 ± 11 years, was studied. Blood pressure, weight, height, lipid profile and blood glucose were measured in all. CIMT and the presence of atherosclerotic plaques were determined by carotid ultrasound. Standard criteria were used to define hypertension, dyslipidemia and diabetes. RESULTS: Mean CIMT in the sample studied was 0.62 ± 0.01 mm and percentile 75 was 0.67. The most important risk factor for a CIMT over percentile 75 and the presence of atherosclerotic plaques was hypertension with attributable risks of 54 and 57%, respectively. CONCLUSIONS: In this sample, the main risk factor for a high CIMT was hypertension.

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Background: Carotid intima media thickness (CIMT) is a marker of cardiovascular damage that can be modified by traditional risk factors. Aim: To determine attributable risk factors for a high CIMT among healthy adults. Material ana Methods: A sample of 1270 individuáis (636 males and 634 femóles) aged 44 ±11 years, was studied. Blood pressure, weight, height, lipidprofile and blood glucose were measured in all. CIMT and thepresence of atheroscleroticplaques were determined by carotid ultrasound. Standard criteria were used to define hypertension, dyslipidemia and diabetes. Results: Mean CIMT in the sample studied was 0.62 ± 0.01 mm and percentile 75 was 0.67. The most important risk factor for a CIMT over percentile 75 and thepresence of atherosclerotic plaques was hypertension with attributable risks of 54 and 57 percent, respectively. Conclusions: In this sample, the main risk factor for a high CIMT was hypertension.

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Background: Waist to height ratio and ultrasensitive C-reactive protein are predictors of the presence of the metabolic syndrome in children. Aim: To determine the proportional risk of metabolic syndrome component clustering in children, using waist to height ratio and ultrasensitive C-reactive protein. Material and Methods: Anthropometric measures, blood pressure, fasting serum lipid profle, blood glucose and ultrasensitive C-reactive protein were determined in 209 children aged 11.5 ± 2 years (50 percent females). The presence of the metabolic syndrome as a function of waist to height ratio and C-reactive protein was modeled using logistic regression equations. The risk of clustering one, two or more components of the metabolic syndrome was calculated. Results: Metabolic syndrome was present in 5 percent of all children and 18 percent of those that were obese. The cut off points for waist to hip ratio and ultrasensitive C-reactive protein were 0.55 and 0.61 mg/L, respectively. For each 0.01 increment in waist to height ratio, the odds ratio of increasing one component of the metabolic syndrome was 1.2 (1.15-1.25) or 15 to 25 percent. The odds ratio for log-transformed ultrasensitive C-reactive protein was 1.62 (1.26-2.09). Excluding waist circumference, the odds ratio of adding one or more components of the metabolic syndrome was 1.05 (1.01-1.09) per 0.01 increment in waist to height ratio, but the odds ratio for C-reactive protein was no longer significant. Conclusions: Waist to height ratio and ultrasensitive C-reactive protein predict the risk of clustering components of the metabolic syndrome in these children.

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Background: A cardiovascular risk score for children, that includes traditional risk factors, obesity, sedentary habits and a family history of cardiovascular disease, has been recently proposed by Spanish researchers. Aim: To apply this score in school age children in Santiago de Chile and correlate its results with markers of subclinical atherosclerotic disease. Material and Methods: Retrospective analysis of data obtained from 209 children, aged 11.5 ± 2 years, studied between 2005 and 2006. Weight, height, blood pressure, ultrasound measurement of carotid intimamedia thickness and fow mediated dilatation of brachial artery and ultrasensible C reactive protein (us PCR) were measured. The Spanish cardiovascular risk score was calculated and correlated with ultrasound parameters and C reactive protein. Results: According to the score, 173 children (83 percent) had a low cardiovascular risk, 28 (13 percent) an intermediate risk and 8 (4 percent) a high risk. There was no association between the cardiovascular risk score and carotid intima-media thickness, fow mediated arterial dilatation and us PCR. Conclusions: No significant association was observed between the proposed cardiovascular risk score and early markers of atherosclerotic disease in this group of children.

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BACKGROUND: Waist to height ratio and ultrasensitive C-reactive protein are predictors of the presence of the metabolic syndrome in children. AIM: To determine the proportional risk of metabolic syndrome component clustering in children, using waist to height ratio and ultrasensitive C-reactive protein. MATERIAL AND METHODS: Anthropometric measures, blood pressure, fasting serum lipid profile, blood glucose and ultrasensitive C-reactive protein were determined in 209 children aged 11.5 ± 2 years (50% females). The presence of the metabolic syndrome as a function of waist to height ratio and C-reactive protein was modeled using logistic regression equations. The risk of clustering one, two or more components of the metabolic syndrome was calculated. RESULTS: Metabolic syndrome was present in 5% of all children and 18% of those that were obese. The cut off points for waist to hip ratio and ultrasensitive C-reactive protein were 0.55 and 0.61 mg/L, respectively. For each 0.01 increment in waist to height ratio, the odds ratio of increasing one component of the metabolic syndrome was 1.2 (1.15-1.25) or 15 to 25%. The odds ratio for log-transformed ultrasensitive C-reactive protein was 1.62 (1.26-2.09). Excluding waist circumference, the odds ratio of adding one or more components of the metabolic syndrome was 1.05 (1.01-1.09) per 0.01 increment in waist to height ratio, but the odds ratio for C-reactive protein was no longer significant. CONCLUSIONS: Waist to height ratio and ultrasensitive C-reactive protein predict the risk of clustering components of the metabolic syndrome in these children.

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BACKGROUND: A cardiovascular risk score for children, that includes traditional risk factors, obesity, sedentary habits and a family history of cardiovascular disease, has been recently proposed by Spanish researchers. AIM: To apply this score in school age children in Santiago de Chile and correlate its results with markers of subclinical atherosclerotic disease. MATERIAL AND METHODS: Retrospective analysis of data obtained from 209 children, aged 11.5 ± 2 years, studied between 2005 and 2006. Weight, height, blood pressure, ultrasound measurement of carotid intimamedia thickness and fow mediated dilatation of brachial artery and ultrasensible C reactive protein (us PCR) were measured. The Spanish cardiovascular risk score was calculated and correlated with ultrasound parameters and C reactive protein. RESULTS: According to the score, 173 children (83%) had a low cardiovascular risk, 28 (13%) an intermediate risk and 8 (4%) a high risk. There was no association between the cardiovascular risk score and carotid intima-media thickness, fow mediated arterial dilatation and us PCR. CONCLUSIONS: No significant association was observed between the proposed cardiovascular risk score and early markers of atherosclerotic disease in this group of children.

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