A differential therapeutic consideration for use of corticosteroids according to established COVID-19 clinical phenotypes in critically ill patients.

Objective: To determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes. Design: A secondary analysis derived from multicenter, observational study. Setting: Critical Care Units. Patients: Adult critically ill patients with confirmed COVID-19 disease admitted to 63 ICUs in Spain. Interventions: Corticosteroids vs. no corticosteroids. Main variables of interest: Three phenotypes were derived by non-supervised clustering analysis from whole population and classified as (A: severe, B: critical and C: life-threatening). We performed a multivariate analysis after propensity optimal full matching (PS) for whole population and weighted Cox regression (HR) and Fine-Gray analysis (sHR) to assess the impact of corticosteroids on ICU mortality according to the whole population and distinctive patient clinical phenotypes. Results: A total of 2017 patients were analyzed, 1171 (58%) with corticosteroids. After PS, corticosteroids were shown not to be associated with ICU mortality (OR: 1.0; 95% CI: 0.98-1.15). Corticosteroids were administered in 298/537 (55.5%) patients of "A" phenotype and their use was not associated with ICU mortality (HR = 0.85 [0.55-1.33]). A total of 338/623 (54.2%) patients in "B" phenotype received corticosteroids. No effect of corticosteroids on ICU mortality was observed when HR was performed (0.72 [0.49-1.05]). Finally, 535/857 (62.4%) patients in "C" phenotype received corticosteroids. In this phenotype HR (0.75 [0.58-0.98]) and sHR (0.79 [0.63-0.98]) suggest a protective effect of corticosteroids on ICU mortality. Conclusion: Our finding warns against the widespread use of corticosteroids in all critically ill patients with COVID-19 at moderate dose. Only patients with the highest inflammatory levels could benefit from steroid treatment.

Objetivo: Evaluar si el uso de corticoesteroides (CC) se asocia con la mortalidad en la unidad de cuidados intensivos (UCI) en la población global y dentro de los fenotipos clínicos predeterminados. Diseño: Análisis secundario de estudio multicéntrico observacional. Ámbito: UCI. Pacientes: Pacientes adultos con COVID-19 confirmado ingresados en 63 UCI de España. Intervención: Corticoides vs. no corticoides. Variables de interés principales: A partir del análisis no supervisado de grupos, 3 fenotipos clínicos fueron derivados y clasificados como: A grave, B crítico y C potencialmente mortal. Se efectuó un análisis multivariado después de un propensity optimal full matching (PS) y una regresión ponderada de Cox (HR) y análisis de Fine-Gray (sHR) para evaluar el impacto del tratamiento con CC sobre la mortalidad en la población general y en cada fenotipo clínico. Resultados: Un total de 2.017 pacientes fueron analizados, 1.171 (58%) con CC. Después del PS, el uso de CC no se relacionó significativamente con la mortalidad en UCI (OR: 1,0; IC 95%: 0,98-1,15). Los CC fueron administrados en 298/537 (55,5%) pacientes del fenotipo A y no se observó asociación significativa con la mortalidad (HR = 0,85; 0,55-1,33). Un total de 338/623 (54,2%) pacientes del fenotipo B recibieron CC sin efecto significativo sobre la mortalidad (HR = 0,72; 0,49-1,05). Por último, 535/857 (62,4%) pacientes del fenotipo C recibieron CC. En este fenotipo, se evidenció un efecto protector de los CC sobre la mortalidad HR (0,75; 0,58-0,98). Conclusión: Nuestros hallazgos alertan sobre el uso indiscriminado de CC a dosis moderadas en todos los pacientes críticos con COVID-19. Solamente pacientes con elevado estado de inflamación podrían beneficiarse con el tratamiento con CC.

Acute-onset smell and taste disorders in the context of COVID-19: a pilot multicentre polymerase chain reaction based case-control study.

BACKGROUND AND PURPOSE: Specific respiratory tract infections, including COVID-19, may cause smell and/or taste disorders (STDs) with increased frequency. The aim was to determine whether new-onset STDs are more frequent amongst COVID-19 patients than influenza patients. METHOD: This was a case-control study including hospitalized patients of two tertiary care centres. Consecutive patients positive for COVID-19 polymerase chain reaction (cases) and patients positive for influenza polymerase chain reaction (historical control sample) were assessed during specific periods, employing a self-reported STD questionnaire. RESULTS: Seventy-nine cases and 40 controls were included. No significant differences were found in basal features between the two groups. New-onset STDs were significantly more frequent amongst cases (31, 39.2%) than in the control group (5, 12.5 %) [adjusted odds ratio 21.4 (2.77-165.4, P = 0.003)]. COVID-19 patients with new-onset STDs were significantly younger than COVID-19 patients without STDs (52.6 ± 17.2 vs. 67.4 ± 15.1, P < 0.001). Amongst COVID-19 patients who presented STDs, 22 (70.9%) recalled an acute onset and it was an initial manifestation in 11 (35.5%). Twenty-five (80.6%) presented smell disorders (mostly anosmia, 14, 45.2%) and 28 (90.3%) taste disorders (mostly ageusia, 14, 45.2%). Only four (12.9 %) reported concomitant nasal obstruction. The mean duration of STD was 7.5 ± 3.2 days and 12 patients (40%) manifested complete recovery after 7.4 ± 2.3 days of onset. CONCLUSION: New-onset STDs were significantly more frequent amongst COVID-19 patients than influenza patients; they usually had an acute onset and were commonly an initial manifestation. The use of STD assessment in anamnesis as a hint for COVID-19 and to support individuals' self-isolation in the current epidemic context is suggested.

Bacterial etiology of community-acquired pneumonia in immunocompetent hospitalized patients and appropriateness of empirical treatment recommendations: an international point-prevalence study.

An accurate knowledge of the epidemiology of community-acquired pneumonia (CAP) is key for selecting appropriate antimicrobial treatments. Very few etiological studies assessed the appropriateness of empiric guideline recommendations at a multinational level. This study aims at the following: (i) describing the bacterial etiologic distribution of CAP and (ii) assessing the appropriateness of the empirical treatment recommendations by clinical practice guidelines (CPGs) for CAP in light of the bacterial pathogens diagnosed as causative agents of CAP. Secondary analysis of the GLIMP, a point-prevalence international study which enrolled adults hospitalized with CAP in 2015. The analysis was limited to immunocompetent patients tested for bacterial CAP agents within 24 h of admission. The CAP CPGs evaluated included the following: the 2007 and 2019 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA), the European Respiratory Society (ERS), and selected country-specific CPGs. Among 2564 patients enrolled, 35.3% had an identifiable pathogen. Streptococcus pneumoniae (8.2%) was the most frequently identified pathogen, followed by Pseudomonas aeruginosa (4.1%) and Klebsiella pneumoniae (3.4%). CPGs appropriately recommend covering more than 90% of all the potential pathogens causing CAP, with the exception of patients enrolled from Germany, Pakistan, and Croatia. The 2019 ATS/IDSA CPGs appropriately recommend covering 93.6% of the cases compared with 90.3% of the ERS CPGs (p < 0.01). S. pneumoniae remains the most common pathogen in patients hospitalized with CAP. Multinational CPG recommendations for patients with CAP seem to appropriately cover the most common pathogens and should be strongly encouraged for the management of CAP patients.

Clinical results of infrared coagulation as a treatment of high-grade anal dysplasia: a systematic review.

BACKGROUND: Anal intraepithelial neoplasia (AIN) (or low/high grade squamous intraepithelial neoplasia (L/HSIL)) is the precursor of anal of early invasive anal cancer. Different treatment options for local ablation of localized lesions have been reported. The aim of this study was to analyze the clinical efficacy and safety of infrared coagulation for the treatment of anal dysplasia. METHODS: A search of the literature was performed in 2019 using PubMed and Cochrane to identify all eligible trials published reporting data on the treatment of anal dysplasia with infrared coagulation. The percentage of squamous cell carcinoma of the the anus that developed in the follow-up and results on major complications after treatment were the primary outcomes. RESULTS: Twenty-four articles were identified from which 6 were selected with a total of 360 patients included, with a median age of 41.8 years. Three studies were prospective and 3 retrospective, only one was a randomized trial. All articles included males, 4 articles included HIV-positive women and only one article included non HIV infected males. No patient developed major complications after infrared coagulation therapy. Pain was the most common symptom found after the procedure in the different series and mild bleeding that did not require transfusion was the most common complication occurring in 4 to 78% of patients. Median follow-up was between 4.7 and 69 months. No patient developed squamous cell carcinoma after infrared treatment. Recurrent HSIL varied from 10 to 38%. Two studies reported results from follow-up of untreated patients showing that between 72 and 93% of them had persistent HSIL at last follow-up and 4.8% developed squamous cell carcinoma. CONCLUSIONS: Infrared coagulation is a safe and effective method for ablation of high-grade anal dysplasia that could help prevent anal cancer. Continued surveillance is recommended due to the risk of recurrence.

Professional burnout in European young oncologists: results of the European Society for Medical Oncology (ESMO) Young Oncologists Committee Burnout Survey.

BACKGROUND: Burnout in health care professionals could have serious negative consequences on quality of patient care, professional satisfaction and personal life. Our aim was to investigate the burnout prevalence, work and lifestyle factors potentially affecting burnout amongst European oncologists ≤40 (YOs). METHODS: A survey was conducted using the validated Maslach Burnout Inventory (MBI) and additional questions exploring work/lifestyle factors. Statistical analyses were carried out to identify factors associated with burnout. RESULTS: Total of 737 surveys (all ages) were collected from 41 European countries. Countries were divided into six regions. Results from 595 (81%) YOs were included (81% medical oncologists; 52% trainees, 62% women). Seventy-one percent of YOs showed evidence of burnout (burnout subdomains: depersonalization 50%; emotional exhaustion 45; low accomplishment 35%). Twenty-two percent requested support for burnout during training and 74% reported no hospital access to support services. Burnout rates were significantly different across Europe (P < 0.0001). Burnout was highest in central European (84%) and lowest in Northern Europe (52%). Depersonalization scores were higher in men compared with women (60% versus 45% P = 0.0001) and low accomplishment was highest in the 26-30 age group (P < 0.01). In multivariable linear regression analyses, European region, work/life balance, access to support services, living alone and inadequate vacation time remained independent burnout factors (P < 0.05). CONCLUSIONS: This is the largest burnout survey in European Young Oncologists. Burnout is common amongst YOs and rates vary across Europe. Achieving a good work/life balance, access to support services and adequate vacation time may reduce burnout levels. Raising awareness, support and interventional research are needed.

High incidence of FXI deficiency in a Spanish town caused by 11 different mutations and the first duplication of F11: Results from the Yecla study.

INTRODUCTION: Factor XI (FXI) deficiency is a rare disorder with molecular heterogeneity in Caucasians but relatively frequent and molecularly homogeneous in certain populations. AIM: To characterize FXI deficiency in a Spanish town of 60 000 inhabitants. METHODS: A total of 324 764 APTT tests were screened during 20 years. FXI was evaluated by FXI:C and by Western blot. Genetic analysis of F11 was performed by sequencing, multiplex ligation-dependent probe amplification and genotyping. RESULTS: Our study identified 46 unrelated cases and 170 relatives with FXI deficiency carrying 12 different genetic defects. p.Cys56Arg, described as founder mutation in the French-Basque population, was identified in 109 subjects from 24 unrelated families. This mutation was also identified in 2% of the general population. p.Cys416Tyr, c.1693G>A and p.Pro538Leu were identified in 7, 6 and 2 unrelated families, respectively. NGS analysis of the whole F11 gene revealed a common haplotype for each of the four recurrent mutations, suggesting a founder effect. The analysis of plasma FXI of four p.Pro538Leu homozygous carriers revealed that this variant was not activated by FXIIa. We identified four mutations previously described in other Caucasian subjects with FXI deficiency (p.Lys536Asn; p.Thr322Ile, p.Arg268Cys and c.325G>A) and four new gene defects: p.(Cys599Tyr) potentially causing a functional deficiency, p.(Ile426Thr), p.(Ile592Thr) and the first worldwide duplication of 1653 bp involving exons 8 and 9. Bleeding was rare and mild. CONCLUSIONS: Our population-cohort study supplies new evidences that FXI deficiency in Caucasians is more common than previously thought and confirmed the wide underlying genetic heterogeneity, caused by both recurrent and sporadic mutations.

Comparison between gadolinium-enhanced 2D T1-weighted gradient-echo and spin-echo sequences in the detection of active multiple sclerosis lesions on 3.0T MRI.

OBJECTIVES: To compare the sensitivity of enhancing multiple sclerosis (MS) lesions in gadolinium-enhanced 2D T1-weighted gradient-echo (GRE) and spin-echo (SE) sequences, and to assess the influence of visual conspicuity and laterality on detection of these lesions. METHODS: One hundred MS patients underwent 3.0T brain MRI including gadolinium-enhanced 2D T1-weighted GRE and SE sequences. The two sets of contrast-enhanced scans were evaluated in random fashion by three experienced readers. Lesion conspicuity was assessed by the image contrast ratio (CR) and contrast-to-noise ratio (CNR). The intracranial region was divided into four quadrants and the impact of lesion location on detection was assessed in each slice. RESULTS: Six hundred and seven gadolinium-enhancing MS lesions were identified. GRE images were more sensitive for lesion detection (0.828) than SE images (0.767). Lesions showed a higher CR in SE than in GRE images, whereas the CNR was higher in GRE than SE. Most misclassifications occurred in the right posterior quadrant. CONCLUSIONS: The gadolinium-enhanced 2D T1-weighted GRE sequence at 3.0T MRI enables detection of enhancing MS lesions with higher sensitivity and better lesion conspicuity than 2D T1-weighted SE. Hence, we propose the use of gadolinium-enhanced GRE sequences rather than SE sequences for routine scanning of MS patients at 3.0T. KEY POINTS: • 2D SE and GRE sequences are useful for detecting active MS lesions. • Which of these sequences is more sensitive at high field remains uncertain. • GRE sequence showed better sensitivity for detecting active MS lesions than SE. • We propose GRE sequence for detecting active MS lesions at 3.0T.

Prognostic value of brachioradialis muscle oxygen saturation index and vascular occlusion test in septic shock patients.

OBJECTIVES: To compare rSO2 (muscle oxygen saturation index) static and dynamic variables obtained by NIRS (Near Infrared Spectroscopy) in brachioradialis muscle of septic shock patients and its prognostic implications. DESIGN: Prospective and observational study. SETTING: Intensive care unit. SUBJECTS: Septic shock patients and healthy volunteers. INTERVENTIONS: The probe of a NIRS device (INVOS 5100) was placed on the brachioradialis muscle during a vascular occlusion test (VOT). VARIABLES: Baseline, minimum and maximum rSO2 values, deoxygenation rate (DeOx), reoxygenation slope (ReOx) and delta value. RESULTS: Septic shock patients (n=35) had lower baseline rSO2 (63.8±12.2 vs. 69.3±3.3%, p<0.05), slower DeOx (-0.54±0.31 vs. -0.91±0.35%/s, p=0.001), slower ReOx (2.67±2.17 vs. 9.46±3.5%/s, p<0.001) and lower delta (3.25±5.71 vs. 15.1±3.9%, p<0.001) when compared to healthy subjects (n=20). Among septic shock patients, non-survivors showed lower baseline rSO2 (57.0±9.6 vs. 69.8±11.3%, p=0.001), lower minimum rSO2 (36.0±12.8 vs. 51.3±14.8%, p<0.01) and lower maximum rSO2 values (60.6±10.6 vs. 73.3±11.2%, p<0.01). Baseline rSO2 was a good mortality predictor (AUC 0.79; 95%CI: 0.63-0.94, p<0.01). Dynamic parameters obtained with VOT did not improve the results. CONCLUSION: Septic shock patients present an important alteration of microcirculation that can be evaluated by NIRS with prognostic implications. Monitoring microvascular reactivity in the brachioradialis muscle using VOT with our device does not seem to improve the prognostic value of baseline rSO2.

Osteochondromas in fibrodysplasia ossificans progressiva: a widespread trait with a streaking but overlooked appearance when arising at femoral bone end.

Metaphyseal bony outgrowths are a well-recognized feature of fibrodysplasia ossificans progressiva (FOP) phenotype, but its genuine frequency, topographic distribution, morphological aspect, and potential implications are not fully established. To better ascertain the frequency and characteristics of osteocartilaginous exostoses in FOP disease, we conducted a cross-sectional radiological study based on all the traceable cases identified in a previous comprehensive national research. Metaphyseal exostoses were present in all the 17 cases of FOP studied. Although most often arising from the distal femoral (where metaphyseal exostoses adopt a peculiar not yet reported appearance) and proximal tibial bones, we have found that they are not restricted to these areas, but rather can be seen scattered at a variety of other skeletal sites. Using nuclear magnetic resonance imaging, we show that these exophytic outgrowths are true osteochondromas. As a whole, these results are in agreement with data coming from the literature review. Our study confirms the presence of metaphyseal osteochondromas as a very frequent trait of FOP phenotype and an outstanding feature of its anomalous skeletal developmental component. In line with recent evidences, this might imply that dysregulation of BMP signaling, in addition to promoting exuberant heterotopic ossification, could induce aberrant chondrogenesis and osteochondroma formation. Unveiling the molecular links between these physiopathological pathways could help to illuminate the mechanisms that govern bone morphogenesis.

Overall survival and central nervous system activity of crizotinib in ROS1-rearranged lung cancer-final results of the EUCROSS trial.

BACKGROUND: In 2019, we reported the first efficacy and safety analysis of EUCROSS, a phase II trial investigating crizotinib in ROS1 fusion-positive lung cancer. At that time, overall survival (OS) was immature and the effect of crizotinib on intracranial disease control remained unclear. Here, we present the final analysis of OS, systemic and intracranial activity, and the impact of co-occurring aberrations. MATERIALS AND METHODS: EUCROSS was a prospective, single-arm, phase II trial. The primary endpoint was best overall response rate (ORR) using RECIST 1.1. Secondary and exploratory endpoints were progression-free survival (PFS), OS, and efficacy in pre-defined subgroups. RESULTS: Median OS of the intention-to-treat population (N = 34) was 54.8 months [95% confidence interval (CI) 20.3 months-not reached (NR); median follow-up 81.4 months] and median all-cause PFS of the response-evaluable population (N = 30) was 19.4 months (95% CI 10.1-32.2 months). Time on treatment was significantly correlated with OS (R = 0.82; P < 0.0001). Patients with co-occurring TP53 aberrations (28%) had a significantly shorter OS [hazard ratio (HR) 11; 95% CI 2.0-56.0; P = 0.006] and all-cause PFS (HR 4.2; 95% CI 1.2-15; P = 0.025). Patients with central nervous system (CNS) involvement at baseline (N = 6; 20%) had a numerically shorter median OS and all-cause PFS. Median intracranial PFS was 32.2 months (95% CI 23.7 months-NR) and the rate of isolated CNS progression was 24%. CONCLUSIONS: Our final analysis proves the efficacy of crizotinib in ROS1-positive lung cancer, but also highlights the devastating impact of TP53 mutations on survival and treatment efficacy. Additionally, our data show that CNS disease control is durable and the risk of CNS progression while on crizotinib treatment is low.

[Prognostic factors in severe traumatic brain injury]. / Factores pronósticos del traumatismo craneoencefálico grave.

OBJECTIVE: To describe the factors associated to mortality of patients with severe traumatic brain injury (TBI). DESIGN: A retrospective observational study was made of patients with severe TBI covering the period between 1 January 2007 and 31 December 2010. SETTING: Virgen de la Vega Hospital, Salamanca (Spain). PATIENTS: All patients hospitalized during the consecutive study period. MAIN VARIABLES OF INTEREST: The dependent variable has been the death rate, while the independent variables were divided into two groups: epidemiological and clinical. RESULTS: The mean patient age was the 50.84 years; 75.5% were males. The average score on the Glasgow Coma Scale (GCS) was 5.09, and the average Injury Severity Score (ISS) was 30.8. Higher mortality was observed in older patients with a higher ISS score. A total of 68.1% of the patients in which intracranial pressure (ICP) was monitored showed intracranial hypertension (ICH). The mortality rate in patients with severe TBI was 36.8%, and was associated mainly to a lower GCS score, the existence of hyperglycemia, coagulopathy, hypoxemia, the presence of mydriasis and shock. The independent mortality indicators in patients with severe TBI were the existence of mydriasis (OR: 32.75), the GCS score (OR: 2.65) and hyperglycemia (OR: 6.08). CONCLUSIONS: The existence of mydriasis, the GCS score and hyperglycemia should be taken into account as prognostic factors in TBI patients.

Bowel obstruction: signs indicating the need for urgent surgery.

Bowel obstruction is common in emergency departments. Obstruction is more common in the small bowel than in the large bowel. The most common cause is postsurgical adhesions. Nowadays, bowel obstruction is diagnosed with multidetector computed tomography (MDCT). MDCT studies for suspected bowel obstruction should focus on four points that need to be mentioned in the report: confirming the obstruction, determining whether there is a single transition point or whether the obstruction is found in a closed loop, establishing the cause of the obstruction, and seeking signs of complications. Identifying signs of ischemia is important in the management of the patient because it enables patients at higher risk of poor outcomes after conservation treatment who could benefit from early surgical intervention to avoid greater morbidity and mortality associated with strangulation and ischemia of the obstructed bowel loop.

Assessing the Equivalence of Brain-Derived Measures from Two 3D T1-Weighted Acquisitions: One Covering the Brain and One Covering the Brain and Spinal Cord.

BACKGROUND AND PURPOSE: In MS, it is common to acquire brain and spinal cord MR imaging sequences separately to assess the extent of the disease. The goal of this study was to see how replacing the traditional brain T1-weighted images (brain-T1) with an acquisition that included both the brain and the cervical spinal cord (cns-T1) affected brain- and spinal cord-derived measures. MATERIALS AND METHODS: Thirty-six healthy controls (HC) and 42 patients with MS were included. Of those, 18 HC and 35 patients with MS had baseline and follow-up at 1 year acquired on a 3T magnet. Two 3D T1-weighted images (brain-T1 and cns-T1) were acquired at each time point. Regional cortical thickness and volumes were determined with FastSurfer, and the percentage brain volume change per year was obtained with SIENA. The spinal cord area was estimated with the Spinal Cord Toolbox. Intraclass correlation coefficients (ICC) were calculated to check for consistency of measures obtained from brain-T1 and cns-T1. RESULTS: Cortical thickness measures showed an ICC >0.75 in 94% of regions in healthy controls and 80% in patients with MS. Estimated regional volumes had an ICC >0.88, and the percentage brain volume change had an ICC >0.79 for both groups. The spinal cord area measures had an ICC of 0.68 in healthy controls and 0.92 in patients with MS. CONCLUSIONS: Brain measurements obtained from 3D cns-T1 are highly equivalent to those obtained from a brain-T1, suggesting that it could be feasible to replace the brain-T1 with cns-T1.

A differential therapeutic consideration for use of corticosteroids according to established COVID-19 clinical phenotypes in critically ill patients.

OBJECTIVE: To determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes. DESIGN: A secondary analysis derived from multicenter, observational study. SETTING: Critical Care Units. PATIENTS: Adult critically ill patients with confirmed COVID-19 disease admitted to 63 ICUs in Spain. INTERVENTIONS: Corticosteroids vs. no corticosteroids. MAIN VARIABLES OF INTEREST: Three phenotypes were derived by non-supervised clustering analysis from whole population and classified as (A: severe, B: critical and C: life-threatening). We performed a multivariate analysis after propensity optimal full matching (PS) for whole population and weighted Cox regression (HR) and Fine-Gray analysis (sHR) to assess the impact of corticosteroids on ICU mortality according to the whole population and distinctive patient clinical phenotypes. RESULTS: A total of 2017 patients were analyzed, 1171 (58%) with corticosteroids. After PS, corticosteroids were shown not to be associated with ICU mortality (OR: 1.0; 95% CI: 0.98-1.15). Corticosteroids were administered in 298/537 (55.5%) patients of "A" phenotype and their use was not associated with ICU mortality (HR=0.85 [0.55-1.33]). A total of 338/623 (54.2%) patients in "B" phenotype received corticosteroids. No effect of corticosteroids on ICU mortality was observed when HR was performed (0.72 [0.49-1.05]). Finally, 535/857 (62.4%) patients in "C" phenotype received corticosteroids. In this phenotype HR (0.75 [0.58-0.98]) and sHR (0.79 [0.63-0.98]) suggest a protective effect of corticosteroids on ICU mortality. CONCLUSION: Our finding warns against the widespread use of corticosteroids in all critically ill patients with COVID-19 at moderate dose. Only patients with the highest inflammatory levels could benefit from steroid treatment.

Using Machine Learning for Predicting the Effect of Mutations in the Initiation Codon.

The effect of mutations has been traditionally predicted by studying what may happen due to the substitution of one amino acid for another one. This approach may be effective for mutations with impact in the function of the protein, but ineffective for mutations in the translation initiation codon. Such mutation might avoid the generation of the protein. Consequently, specific methods for predicting the effect of mutations in the translation initiation codon are needed. We propose a method for predicting the effect of mutations in the canonical translation initiation codon based on a biological model that considers specific features of such mutations, like the distance to a potential alternative initiation codon. Our predictor has been developed using tree-based machine learning algorithms and data extracted from Ensembl. Our final model is able to detect whether a mutation in the canonical initiation codon is deleterious or benign with a precision of 44.28% and an accuracy of 98.32%, which improves the results of state of the art tools such as PolyPhen, SIFT, or CADD for this type of mutation.