ESMO recommendations on the standard methods to detect NTRK fusions in daily practice and clinical research.

BACKGROUND: NTRK1, NTRK2 and NTRK3 fusions are present in a plethora of malignancies across different histologies. These fusions represent the most frequent mechanism of oncogenic activation of these receptor tyrosine kinases, and biomarkers for the use of TRK small molecule inhibitors. Given the varying frequency of NTRK1/2/3 fusions, crucial to the administration of NTRK inhibitors is the development of optimal approaches for the detection of human cancers harbouring activating NTRK1/2/3 fusion genes. MATERIALS AND METHODS: Experts from several Institutions were recruited by the European Society for Medical Oncology (ESMO) Translational Research and Precision Medicine Working Group (TR and PM WG) to review the available methods for the detection of NTRK gene fusions, their potential applications, and strategies for the implementation of a rational approach for the detection of NTRK1/2/3 fusion genes in human malignancies. A consensus on the most reasonable strategy to adopt when screening for NTRK fusions in oncologic patients was sought, and further reviewed and approved by the ESMO TR and PM WG and the ESMO leadership. RESULTS: The main techniques employed for NTRK fusion gene detection include immunohistochemistry, fluorescence in situ hybridization (FISH), RT-PCR, and both RNA-based and DNA-based next generation sequencing (NGS). Each technique has advantages and limitations, and the choice of assays for screening and final diagnosis should also take into account the resources and clinical context. CONCLUSION: In tumours where NTRK fusions are highly recurrent, FISH, RT-PCR or RNA-based sequencing panels can be used as confirmatory techniques, whereas in the scenario of testing an unselected population where NTRK1/2/3 fusions are uncommon, either front-line sequencing (preferentially RNA-sequencing) or screening by immunohistochemistry followed by sequencing of positive cases should be pursued.

Evidence-based guides in tracheostomy use in critical patients. / Guías basadas en la evidencia para el uso de traqueostomía en el paciente crítico.

OBJECTIVES: Provide evidence based guidelines for tracheostomy in critically ill adult patients and identify areas needing further research. METHODS: A task force composed of representatives of 10 member countries of the Pan-American and Iberic Federation of Societies of Critical and Intensive Therapy Medicine and of the Latin American Critical Care Trial Investigators Network developed recommendations based on the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS: The group identified 23 relevant questions among 87 issues that were initially identified. In the initial search, 333 relevant publications were identified of which 226 publications were chosen. The task force generated a total of 19 recommendations: 10 positive (1B=3, 2C=3, 2D=4) and 9 negative (1B=8, 2C=1). A recommendation was not possible in six questions. CONCLUSION: Percutaneous techniques are associated with a lower risk of infections compared to surgical tracheostomy. Early tracheostomy only seems to reduce the duration of ventilator use but not the incidence of pneumonia, the length of stay, or the long-term mortality rate. The evidence does not support the use of routine bronchoscopy guidance or laryngeal masks during the procedure. Finally, proper prior training is as important or even a more significant factor in reducing complications than the technique used.

Precision medicine in NSCLC and pathology: how does ALK fit in the pathway?

The evolution of personalised medicine in lung cancer has dramatically impacted diagnostic pathology. Current challenges centre on the growing demands placed on small tissue samples by molecular diagnostic techniques. In this review, expert recommendations are provided regarding successful identification of anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC). Steps to correctly process and conserve tumour tissue during diagnostic testing are essential to ensure tissue availability. For example, storing extra tissue sections ready for molecular diagnostic steps allows faster testing and preserves tissue. Fluorescence in situ hybridisation (FISH) is commonly used to detect ALK rearrangements, with most laboratories favouring screening by immunohistochemistry followed by a confirmatory FISH assay. Reverse transcription-polymerase chain reaction can also identify ALK fusion gene mRNA transcripts but can be limited by the quality of RNA and the risk that rare fusion variants may not be captured. Next-generation sequencing (NGS) technology has recently provided an alternative method for detecting ALK rearrangements. While current experience is limited, NGS is set to become the most efficient approach as an increasing number of genetic abnormalities is required to be tested. Upfront, reflex testing for ALK gene rearrangement should become routine as ALK tyrosine kinase inhibitor therapy moves into the first-line setting. Guidelines recommend that EGFR and ALK tests are carried out in parallel on all confirmed and potential adenocarcinomas, and this is more efficient in terms of tissue usage and testing turnaround time for both of these actionable gene alterations. The practice of sequential testing is not recommended. Identification of ALK rearrangements is now essential for the diagnosis of NSCLC, underpinned by the benefits of ALK inhibitors. As scientific understanding and diagnostic technology develops, ALK testing will continue to be an evolving and challenging paradigm.

Acute toxicity of anionic and non-ionic surfactants to aquatic organisms.

The environmental risk of surfactants requires toxicity measurements. As different test organisms have different sensitivity to the toxics, it is necessary to establish the most appropriate organism to classify the surfactant as very toxic, toxic, harmful or safe, in order to establish the maximum permissible concentrations in aquatic ecosystems. We have determined the toxicity values of various anionic surfactants ether carboxylic derivatives using four test organisms: the freshwater crustacean Daphnia magna, the luminescent bacterium Vibrio fischeri, the microalgae Selenastrum capricornutum (freshwater algae) and Phaeodactylum tricornutum (seawater algae). In addition, in order to compare and classify the different families of surfactants, we have included a compilation of toxicity data of surfactants collected from literature. The results indicated that V. fischeri was more sensitive to the toxic effects of the surfactants than was D. magna or the microalgae, which was the least sensitive. This result shows that the most suitable toxicity assay for surfactants may be the one using V. fischeri. The toxicity data revealed considerable variation in toxicity responses with the structure of the surfactants regardless of the species tested. The toxicity data have been related to the structure of the surfactants, giving a mathematical relationship that helps to predict the toxic potential of a surfactant from its structure. Model-predicted toxicity agreed well with toxicity values reported in the literature for several surfactants previously studied. Predictive models of toxicity is a handy tool for providing a risk assessment that can be useful to establish the toxicity range for each surfactant and the different test organisms in order to select efficient surfactants with a lower impact on the aquatic environment.

Temperature evaluation of dental implant surface irradiated with high-power diode laser.

The prevalence of peri-implantitis and the absence of a standard approach for decontamination of the dental implant surface have led to searches for effective therapies. Since the source of diode lasers is portable, has reduced cost, and does not cause damage to the titanium surface of the implant, high-power diode lasers have been used for this purpose. The effect of laser irradiation on the implants is the elevation of the temperature surface. If this elevation exceeds 47 °C, the bone tissue is irreversibly damaged, so for a safety therapy, the laser parameters should be controlled. In this study, a diode laser of GaAsAl was used to irradiate titanium dental implants, for powers 1.32 to 2.64 W (real) or 2.00 to 4.00 W (nominal), in continuous/pulsed mode DC/AC, with exposure time of 5/10 s, with/without air flow for cooling. The elevation of the temperature was monitored in real time in two positions: cervical and apical. The best results for decontamination using a 968-nm diode laser were obtained for a power of 1.65 and 1.98 W (real) for 10 s, in DC or AC mode, with an air flow of 2.5 l/min. In our perspective in this article, we determine a suggested approach for decontamination of the dental implant surface using a 968-nm diode laser.

Effects of Combining Feed Grade Urea and a Slow-release Urea Product on Performance, Dietary Energetics and Carcass Characteristics of Feedlot Lambs Fed Finishing Diets with Different Starch to Acid Detergent Fiber Ratios.

Recent findings have shown that microbial nitrogen flow and digestible energy of diets are increased when urea is combined with a slow-release urea (SRU) in diets with a starch to acid detergent fibre ratio (S:F) 4:1. This affect is attributable to enhanced synchrony between ruminal N availability for microbial growth and carbohydrate degradation. To verify the magnitude of this effects on lamb performance, an experiment was conducted to evaluate the effects of combining urea and a SRU in diets containing S:F ratios of 3:1, 4:1, or 5:1 on performance, dietary energetics and carcass characteristics of finishing lambs. For that, 40 Pelibuey×Katahdin lambs (36.65±3 kg) were assigned to one of five weight groupings in 20 pens (5 repetition/treatments). The S:F ratio in the diet was manipulated by partially replacing the corn grain and dried distiller's grain with solubles by forage (wheat straw) and soybean meal to reach S:F ratios of 3:1, 4:1 or 5:1. An additional treatment of 4:1 S:F ratio with 0.8% urea as the sole source of non-protein nitrogen was used as a reference for comparing the effect of urea combination vs. conventional urea at the same S:F ratio. There were no treatment effects on dry matter intake (DMI). Compared the urea combination vs urea at the same S:F ratio, urea combination increased (p<0.01) average daily gain (ADG, 18.3%), gain for feed (G:F, 9.5%), and apparent energy retention per unit DMI (8.2%). Irrespective of the S:F ratio, the urea combination improved the observed-to-expected dietary ratio and apparent retention per unit DMI was maximal (quadratic effect, p≤0.03) at an S:F ratio of 4:1, while the conventional urea treatment did not modify the observed-to-expected net energy ratio nor the apparent retention per unit DMI at 4:1 S:F ratio. Urea combination group tended (3.8%, p = 0.08) to have heavier carcasses with no effects on the rest of carcass characteristics. As S:F ratio increased, ADG, G:F, dietary net energy, carcass weight, dressing percentage and longissimus thoracis (LM) area increased linearly (p≤0.02). Combining urea and a slow-release urea product results in positive effects on growth performance and dietary energetics, but the best responses are apparently observed when there is a certain proportion (S:F ratio = 4:1) of starch to acid detergent fibre in the diet.

Acute Respiratory Distress: from syndrome to disease.

The acute respiratory distress syndrome (ARDS) is currently one of the most important critical entities given its high incidence, rate of mortality, long-term sequelae and non-specific pharmacological treatment. The histological hallmark of ARDS is diffuse alveolar damage (DAD). Approximately 50% of ARDS patients present DAD, the rest is made up of a heterogeneous group of histological patterns, many of which correspond to a well-recognized disease. For that reason, if these patterns could be diagnosed, patients could benefit from a treatment. Recently, the effect of DAD in clinical and analytical evolution of ARDS has been demonstrated, so the classical approach to ARDS as an entity defined solely by clinical, radiological and gasometrical variables should be reconsidered. This narrative review aims to examine the need to evolve from the concept of ARDS as a syndrome to ARDS as a specific disease. So we have raised 4 critical questions: a) What is a disease?; b) what is DAD?; c) how is DAD considered according to ARDS definition?, and d) what is the relationship between ARDS and DAD?

Stromal disrupting effects of nab-paclitaxel in pancreatic cancer.

BACKGROUND: Nab-paclitaxel and gemcitabine have demonstrated a survival benefit over gemcitabine alone in advanced pancreatic cancer (PDA). This study aimed to investigate the clinical, biological, and imaging effects of the regimen in patients with operable PDA. METHODS: Patients with operable PDA received two cycles of nab-paclitaxel and gemcitabine before surgical resection. FDG-PET and CA19.9 tumour marker levels were used to measure clinical activity. Effects on tumour stroma were determined by endoscopic ultrasound (EUS) elastography. The collagen content and architecture as well as density of cancer-associated fibroblasts (CAFs) were determined in the resected surgical specimen and compared with a group of untreated and treated with conventional chemoradiation therapy controls. A co-clinical study in a mouse model of PDA was conducted to differentiate between the effects of nab-paclitaxel and gemcitabine. RESULTS: A total of 16 patients were enrolled. Treatment resulted in significant antitumour effects with 50% of patients achieving a >75% decrease in circulating CA19.9 tumour marker and a response by FDG-PET. There was also a significant decrement in tumour stiffness as measured by EUS elastography. Seven of 12 patients who completed treatment and were operated had major pathological regressions. Analysis of residual tumours showed a marked disorganised collagen with a very low density of CAF, which was not observed in the untreated or conventionally treated control groups. The preclinical co-clinical study showed that these effects were specific of nab-paclitaxel and not gemcitabine. CONCLUSION: These data suggest that nab-paclitaxel and gemcitabine decreases CAF content inducing a marked alteration in cancer stroma that results in tumour softening. This regimen should be studied in patients with operable PDA.

Influence of Ionophore Supplementation on Growth Performance, Dietary Energetics and Carcass Characteristics in Finishing Cattle during Period of Heat Stress.

Forty-eight crossbred heifers (378.1±18 kg) were used in a 56-d feeding trial (four pens per treatment in a randomised complete block design) to evaluate the influence of ionophore supplementation on growth performance, dietary energetics and carcass characteristics in finishing cattle during a period of heat stress. Heifers were fed a diet based on steam-flaked corn (2.22 Mcal NEm/kg) with and without an ionophore. Treatments were: i) control, no ionophore; ii) 30 mg/kg monensin sodium (RUM30); iii) 20 mg/kg lasalocid sodium (BOV20), and iv) 30 mg/kg lasalocid sodium (BOV30). Both dry matter intake (DMI) and climatic variables were measured daily and the temperature humidity index (THI) was estimated. The maximum THI during the study averaged 93, while the minimum was 70 (THI average = 79.2±2.3). Compared to controls, monensin supplementation did not influence average daily gain, the estimated NE value of the diet, or observed-to-expected DMI, but tended (p = 0.07) to increase (4.8%) gain to feed. Compared to controls, the group fed BOV30 increased (p≤0.03) daily gain (11.8%), gain to feed (8.3%), net energy of the diet (5%), and observed-to-expected DMI (5.2%). Daily weight gain was greater (7.6%, p = 0.05) for heifers fed BOV30 than for heifers fed MON30. Otherwise, differences between the two treatments in DMI, gain to feed, and dietary NE were not statistically significant (p>0.11). Plotting weekly intakes versus THI, observed intake of controls was greater (p<0.05) at THI values ≤77 than ionophore groups. When THI values were greater than 79, DMI of control and MON30 were not different (p = 0.42), although less than that of groups fed lasalocid (p = 0.04). Variation in energy intake was lower (p>0.05) in the ionophores group (CV = 1.7%) than in the control group (CV = 4.5%). Inclusion of ionophores in the diet resulted in relatively minor changes in carcass characteristics. It is concluded that ionophore supplementation did not exacerbate the decline of DM intake in heat-stressed cattle fed a high-energy finishing diet; on the contrary, it stabilised feed intake and favoured feed efficiency. Ionophore supplementation reduced estimated maintenance coefficients around 10% in finishing cattle during a period of heat stress. This effect was greatest for heifers supplemented with 30 mg lasalocid/kg of diet.

New prognostic model in patients with advanced urothelial carcinoma treated with second-line immune checkpoint inhibitors.

BACKGROUND: Bellmunt Risk Score, based on Eastern Cooperative Oncology Group (ECOG) performance status (PS), hemoglobin levels and presence of liver metastases, is the most established prognostic algorithm for patients with advanced urothelial cancer (aUC) progressing after platinum-based chemotherapy. Nevertheless, existing algorithms may not be sufficient following the introduction of immunotherapy. Our aim was to develop an improved prognostic model in patients receiving second-line atezolizumab for aUC. METHODS: Patients with aUC progressing after cisplatin/carboplatin-based chemotherapy and enrolled in the prospective, single-arm, phase IIIb SAUL study were included in this analysis. Patients were treated with 3-weekly atezolizumab 1200 mg intravenously. The development and internal validation of a prognostic model for overall survival (OS) was performed using Cox regression analyses, bootstrapping methods and calibration. RESULTS: In 936 patients, ECOG PS, alkaline phosphatase, hemoglobin, neutrophil-to-lymphocyte ratio, liver metastases, bone metastases and time from last chemotherapy were identified as independent prognostic factors. In a 4-tier model, median OS for patients with 0-1, 2, 3-4 and 5-7 risk factors was 18.6, 10.4, 4.8 and 2.1 months, respectively. Compared with Bellmunt Risk Score, this model provided enhanced prognostic separation, with a c-index of 0.725 vs 0.685 and increment in c-statistic of 0.04 (p<0.001). Inclusion of PD-L1 expression did not improve the model. CONCLUSIONS: We developed and internally validated a prognostic model for patients with aUC receiving postplatinum immunotherapy. This model represents an improvement over the Bellmunt algorithm and could aid selection of patients with aUC for second-line immunotherapy. TRIAL REGISTRATION NUMBER: NCT02928406.

A comparison of three methods for detecting KRAS mutations in formalin-fixed colorectal cancer specimens.

BACKGROUND: KRAS mutation testing is required to select patients with metastatic colorectal cancer (CRC) to receive anti-epidermal growth factor receptor antibodies, but the optimal KRAS mutation test method is uncertain. METHODS: We conducted a two-site comparison of two commercial KRAS mutation kits - the cobas KRAS Mutation Test and the Qiagen therascreen KRAS Kit - and Sanger sequencing. A panel of 120 CRC specimens was tested with all three methods. The agreement between the cobas test and each of the other methods was assessed. Specimens with discordant results were subjected to quantitative massively parallel pyrosequencing (MPP). DNA blends were tested to determine detection rates at 5% mutant alleles. RESULTS: Reproducibility of the cobas test between sites was 98%. Six mutations were detected by cobas that were not detected by Sanger, and five were confirmed by MPP. The cobas test detected eight mutations which were not detected by the therascreen test, and seven were confirmed by MPP. Detection rates with 5% mutant DNA blends were 100% for the cobas and therascreen tests and 19% for Sanger. CONCLUSION: The cobas test was reproducible between sites, and detected several mutations that were not detected by the therascreen test or Sanger. Sanger sequencing had poor sensitivity for low levels of mutation.

Acute toxicity of alkylpolyglucosides to Vibrio fischeri, Daphnia magna and microalgae: a comparative study.

In this paper, toxicity values of alkylpolyglucosides have been determined by applying the 24-h immobilization test with Daphnia magna, the LumiStox(®) 300 test which employs the luminescent bacteria Photobacterium phosphoreum and the test with Selenastrum capricornutum. Three alkylpolyglucosides with different alkyl chain and degree of polymerisation have been tested. For all tests, the results indicated that Vibrio fischeri was more sensitive to toxic effects from alkylpolyglucosides than was D. magna or S. capricornutum. The results demonstrate considerable variation in toxicity responses within structurally related glucose-based surfactants regardless of the species tested. The toxicity increased as the critical micelle concentration decreased, and as the alkyl chain length and resultant hydrophobicity increased.

Culex quinquefasciatus predominance during integrated mosquito surveillance in an urban area of the Brazilian Amazon.

The presence and establishment of Culicidae in urban areas increase the transmissibility of tropical diseases, since some species can participate as vectors of pathogens. Thus, this study aimed to evaluate the indoor and outdoor abundance of immature and adult populations of Culicidae at the urban area of Porto Velho, Rondônia. Mosquitoes were captured using electric aspirators and ovitraps in September and December 2018 in 27 households spread over nine neighborhoods. A total of 2,342 specimens were collected, distributed among five species, of which Culex quinquefasciatus (Say, 1823), Aedes aegypti (Linnaeus, 1762) and Aedes albopictus (Skuse, 1894) were the most abundant. Considering the sum total obtained by both techniques, more mosquitoes were captured indoors than outdoors. However, the GLM estimates for the ovitrap technique showed that immature Ae. aegypti, Ae. albopictus and Cx. quinquefasciatus were significantly more abundant in the outdoors, on average. The opposite result was observed for electrical aspiration, in which Ae. aegypti and Cx. quinquefasciatus adults were more abundant indoors. The average number of winged Ae. albopictus showed no significant difference between indoors and outdoors. Our findings corroborate the data on the abundance and incidence of these three species in other regions of Brazil, highlighting the need for continuous surveillance due to their importance in disease transmission to humans. We also demonstrated that the ovitrap is a sensitive device to monitor Cx. quinquefasciatus larvae and wild species that occasionally frequent urban areas, and thus can be used for surveillance, especially when there are budgetary constraints. Therefore, we emphasize that the combination of techniques, in addition to identifying which species and which stage of development are more frequent inside and outside households, also allows for the implementation of specific and integrated control measures.

Recommendations of the Society of Thoracic Surgery and the Section of Cardiothoracic and Vascular Surgery of the Spanish Society of Anesthesia, Resuscitation and Pain Therapy, for patients undergoing lung surgery included in an intensified recovery program.

In recent years, multidisciplinary programs have been implemented that include different actions during the pre, intra and postoperative period, aimed at reducing perioperative stress and therefore improving the results of patients undergoing surgical interventions. Initially, these programs were developed for colorectal surgery and from there they have been extended to other surgeries. Thoracic surgery, considered highly complex, like other surgeries with a high postoperative morbidity and mortality rate, may be one of the specialties that most benefit from the implementation of these programs. This review presents the recommendations made by different specialties involved in the perioperative care of patients who require resection of a lung tumor. Meta-analyzes, systematic reviews, randomized and non-randomized controlled studies, and retrospective studies conducted in patients undergoing this type of intervention have been taken into account in preparing the recommendations presented in this guide. The GRADE scale has been used to classify the recommendations, assessing on the one hand the level of evidence published on each specific aspect and, on the other hand, the strength of the recommendation with which the authors propose its application. The recommendations considered most important for this type of surgery are those that refer to pre-habilitation, minimization of surgical aggression, excellence in the management of perioperative pain and postoperative care aimed at providing rapid postoperative rehabilitation.

Composite anatomical-clinical-molecular prognostic model in non-small cell lung cancer.

The objective of the present study was to elaborate a survival model that integrates anatomic factors, according to the 2010 seventh edition of the tumour, node and metastasis (TNM) staging system, with clinical and molecular factors. Pathologic TNM descriptors (group A), clinical variables (group B), laboratory parameters (group C) and molecular markers (tissue microarrays; group D) were collected from 512 early-stage nonsmall cell lung cancer (NSCLC) patients with complete resection. A multivariate analysis stepped supervised learning classification algorithm was used. The prognostic performance by groups was: areas under the receiver operating characteristic curve (C-index): 0.67 (group A), 0.65 (Group B), 0.57 (group C) and 0.65 (group D). Considering all variables together selected for each of the four groups (integrated group) the C-index was 0.74 (95% CI 0.70-0.79), with statistically significant differences compared with each isolated group (from p = 0.006 to p < 0.001). Variables with the greatest prognostic discrimination were the presence of another ipsilobar nodule and tumour size > 3 cm, followed by other anatomical and clinical factors, and molecular expressions of phosphorylated mammalian target of rapamycin (phospho-mTOR), Ki67cell proliferation index and phosphorylated acetyl-coenzyme A carboxylase. This study on early-stage NSCLC shows the benefit from integrating pathological TNM, clinical and molecular factors into a composite prognostic model. The model of the integrated group classified patients with significantly higher accuracy compared to the TNM 2010 staging.

Effect of concentration on the primary and ultimate biodegradation of alkylpolyglucosides in aerobic biodegradation tests.

This study examines the primary and ultimate biodegradation of a non-ionic surfactant, an alkylpolyglucoside, in ready biodegradability tests. The surfactant concentration was tested by the anthrone method, while the ultimate biodegradation (mineralization) was analyzed by the total organic carbon determinations. The influence of the concentration on the extent of primary and ultimate biodegradation and the kinetics of degradation also were determined. The primary and ultimate biodegradation was studied at different initial concentrations-15, 25, 50, 75, and 100 mg/L. The increasing concentration of test chemical from 15 to 100 mg/L resulted in a decrease in the relative maximum mineralization rate and longer estimated lag times by a factor of approximately 4.3. During the degradative process, two different stages were noted; these are better described with Quiroga and first-order kinetic models, respectively. For the study of the influence of concentration, the parameters characteristic of the biodegradation profiles in the different biodegradation assays were evaluated.

Steroids and mortality in non-critically ill COVID-19 patients: a propensity score-weighted study in a Chilean cohort.

OBJECTIVES: The aim of this study was to evaluate the impact on 30-day mortality of early use of corticosteroids in COVID-19 patients with supplementary oxygen requirements and without invasive mechanical ventilation at the initiation of therapy. METHODS: All patients hospitalized with COVID-19 between April 15 and July 15, 2020, and requiring supplementary oxygen, were prospectively included in a database. Patients who died or required intubation within the first 48 hours were excluded. Patients who received corticosteroids within the first 5 days of hospitalization and at least 24 hours prior to intubation were allocated to the 'early corticosteroids' group. To compare both populations and adjust for non-random treatment assignment bias, a weight-adjusted propensity score model was used. RESULTS: In total, 571 patients met the inclusion criteria, 520 had sufficient information for the analysis. Of these, 233 received early corticosteroids and 287 did not. Analysis showed a reduction of 8.5% (p = 0.038) in 30-day mortality in the early corticosteroid group. The reduction in mortality was not significant when patients with corticosteroid initiation between day 5 and day 8 of hospitalization were included. CONCLUSION: Early corticosteroid use reduced mortality in patients with pneumonia due to COVID-19, who required supplementary oxygen but not initial invasive mechanical ventilation.

[Tumors that cause bone metastases]. / Tumores que producen metástasis óseas.

INTRODUCTION: A metastasis is the tumor cell capacity to migrate from the primary tumor and implant itself in tissues of an organ at a distance by hematogenous, lymphatic or contiguity. The main causes of bone metastases are: breast, prostate and lung cancer. It usually occurs in patients over 50 years of age. There is a predilection for metastasizing to the axial skeleton. OBJECTIVE: To determine the frequency of tumors that produce bone metastases in our institution. MATERIAL AND METHODS: Observational, cross-sectional, descriptive study, for retrospective analysis of the cases of patients diagnosed with bone metastases. RESULTS: 193 cases; 121 women and 72 men with an age range of 42 to 84 years. Cancers associated with bone metastases were breast, lung, prostate, cervical and renal cancers; to a lesser extent other such as colon, thyroid, liver and skin. The most affected bones were axial skeleton: lumbar and dorsal spine, and in appendicular skeleton the femur in the diaphysiary region and in the humerus the proximal third. At present it has not been possible to improve the effectiveness of timely detection strategies, so bone pain should begin with a protocol of tumor suspicion. CONCLUSIONS: More than 80% of the patients came for fracture. All patients had a history of pain greater than 12 months with no prior study protocol.

INTRODUCCIÓN: Una metástasis es la capacidad celular tumoral para migrar del tumor primario e implantarse en tejidos de un órgano a distancia por vía hematógena, linfática o contigüidad. Las principales causas de metástasis óseas son: cáncer de mama, próstata y pulmón. Habitualmente se da en pacientes mayores de 50 años. Existe predilección por metastatizar al esqueleto axial. OBJETIVO: Determinar la frecuencia de los tumores que producen metástasis óseas en nuestra institución. MATERIAL Y MÉTODOS: Estudio observacional, transversal, descriptivo, para análisis retrospectivo de los casos con diagnóstico de metástasis ósea. RESULTADOS: Ciento noventa y tres casos; 121 mujeres y 72 hombres con rango de edad de 42 a 84 años. Los cánceres asociados a metástasis ósea fueron cáncer de mama, pulmón, próstata, cervicouterino y renal; en menor proporción otros como colon, tiroides, hígado y piel. Los huesos más afectados fueron esqueleto axial: columna lumbar y dorsal; en esqueleto apendicular el fémur en la región diafisaria y en el húmero el tercio proximal. En la actualidad, no se ha logrado mejorar la efectividad de estrategias de detección oportuna, por lo que los cuadros de dolor óseo deben iniciar con un protocolo de sospecha tumoral. CONCLUSIONES: Más de 80% de los pacientes acudieron por fractura. Todos tenían historial de dolor mayor a 12 meses sin protocolo de estudio previo.