Results of phase 2 randomized multi-center study to evaluate the safety and efficacy of infusion of memory T cells as adoptive therapy in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia and/or lymphopenia (RELEASE NCT04578210).

BACKGROUND AIMS: There are currently no effective anti-viral treatments for coronavirus disease 2019 (COVID-19)-hospitalized patients with hypoxemia. Lymphopenia is a biomarker of disease severity usually present in patients who are hospitalized. Approaches to increasing lymphocytes exerting an anti-viral effect must be considered to treat these patients. Following our phase 1 study, we performed a phase 2 randomized multicenter clinical trial in which we evaluated the efficacy of the infusion of allogeneic off-the-shelf CD45RA- memory T cells containing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells from convalescent donors plus the standard of care (SoC) versus just the SoC treatment. METHODS: Eighty-four patients were enrolled in three Spanish centers. The patients were randomized into the infusion of 1 × 106/kg CD45RA- memory T cells or the SoC. We selected four unvaccinated donors based on the expression of interferon gamma SARS-CoV-2-specific response within the CD45RA- memory T cells and the most frequent human leukocyte antigen typing in the Spanish population. RESULTS: We analyzed data from 81 patients. The primary outcome for recovery, defined as the proportion of participants in each group with normalization of fever, oxygen saturation sustained for at least 24 hours and lymphopenia recovery through day 14 or at discharge, was met for the experimental arm. We also observed faster lymphocyte recovery in the experimental group. We did not observe any treatment-related adverse events. CONCLUSIONS: Adoptive cell therapy with off-the-shelf CD45RA- memory T cells containing SAR-CoV-2-specific T cells is safe, effective and accelerates lymphocyte recovery of patients with COVID-19 pneumonia and/or lymphopenia. TRIAL REGISTRATION: NCT04578210.

Donor selection for adoptive cell therapy with CD45RA- memory T cells for patients with coronavirus disease 2019, and dexamethasone and interleukin-15 effects on the phenotype, proliferation and interferon gamma release.

BACKGROUND AIMS: We have previously demonstrated the safety and feasibility of adoptive cell therapy with CD45RA- memory T cells containing severe acute respiratory syndrome coronavirus 2-specific T cells for patients with coronavirus disease 2019 from an unvaccinated donor who was chosen based on human leukocyte antigen compatibility and cellular response. In this study, we examined the durability of cellular and humoral immunity within CD45RA- memory T cells and the effect of dexamethasone, the current standard of care treatment, and interleukin-15, a cytokine critically involved in T-cell maintenance and survival. METHODS: We performed a longitudinal analysis from previously severe acute respiratory syndrome coronavirus 2-infected and infection-naïve individuals covering 21 months from infection and 10 months after full vaccination with the BNT162b2 Pfizer/BioNTech vaccine. RESULTS: We observed that cellular responses are maintained over time. Humoral responses increased after vaccination but were gradually lost. In addition, dexamethasone did not alter cell functionality or proliferation of CD45RA- T cells, and interleukin-15 increased the memory T-cell activation state, regulatory T cell expression, and interferon gamma release. CONCLUSIONS: Our results suggest that the best donors for adoptive cell therapy would be recovered individuals and 2 months after vaccination, although further studies with larger cohorts would be needed to confirm this finding. Dexamethasone did not affect the characteristics of the memory T cells at a concentration used in the clinical practice and IL-15 showed a positive effect on SARS-CoV-2-specific CD45RA- T cells.

Metabolic labeling of RNA uncovers the contribution of transcription and decay rates on hypoxia-induced changes in RNA levels.

Cells adapt to environmental changes, including fluctuations in oxygen levels, through the induction of specific gene expression programs. However, most transcriptomic studies do not distinguish the relative contribution of transcription, RNA processing, and RNA degradation processes to cellular homeostasis. Here we used metabolic labeling followed by massive parallel sequencing of newly transcribed and preexisting RNA fractions to simultaneously analyze RNA synthesis and decay in primary endothelial cells exposed to low oxygen tension. We found that changes in transcription rates induced by hypoxia are the major determinant of changes in RNA levels. However, degradation rates also had a significant contribution, accounting for 24% of the observed variability in total mRNA. In addition, our results indicated that hypoxia led to a reduction of the overall mRNA stability from a median half-life in normoxia of 8.7 h, to 5.7 h in hypoxia. Analysis of RNA content per cell confirmed a decrease of both mRNA and total RNA in hypoxic samples and that this effect is dependent on the EGLN/HIF/TSC2 axis. This effect could potentially contribute to fundamental global responses such as inhibition of translation in hypoxia. In summary, our study provides a quantitative analysis of the contribution of RNA synthesis and stability to the transcriptional response to hypoxia and uncovers an unexpected effect on the latter.

Impact on daily clinical practice of the latest evidence on percutaneous closure of patent foramen ovale after cryptogenic stroke: a single-center experience.

INTRODUCTION AND OBJECTIVES: At the end of 2017, three clinical trials demonstrated that, in selected patients, percutaneous closure of patent foramen ovale (PFO) after cryptogenic stroke (CS) reduces the risk of recurrence. Our aim was to determine the impact of these findings on routine clinical practice in a tertiary hospital. METHODS: Patients with CS and percutaneous closure of PFO during 2001-2020 were included. The clinical characteristics of the patient and the anatomical characteristics of the foramen were analyzed. Based on both, the closure indications were classified into three groups according to the latest European recommendations and were analyzed in two periods, before and after the publication date of the clinical trials. RESULTS: A total of 293 patients were included. The mean age was 49 ± 11 years, and 15% were older than 60 years. The median RoPE score was 6 [p25-75, 5-7] and 75% had complex anatomy (CA). After the publication of the studies, the frequency of CA and the mean age of the patients were significantly higher (89% vs. 69% p < 0.0005 and 51 ± 11 vs. 48 ± 11 years, p = 0.02, respectively), and the RoPE score, significantly lower (5 [5-7] versus 6 [5-7], p = 0.02). Inadequate closure indications were significantly reduced (8% vs. 18%, p = 0.02). CONCLUSION: After the publication of clinical trials that have shown benefit of PFO closure after CS, the number of inappropriate indications for closure has decreased significantly in our institution, with a higher percentage of CA, despite a clinical profile suggestive of lower causal probability of PFO.

Psychometric properties of the Emotional Quotient Inventory: Youth Version-EQ-i:YV in Spanish adolescents with Down syndrome.

BACKGROUND: The people with Down syndrome who are now adolescents can face a self-report questionnaire with guarantees of being answered with validity to evaluate areas of development that traditionally have not been able to be evaluated. This is the case of emotional intelligence, measured in this research with the Emotional Quotient Inventory: Youth Version-EQ-i:YV. AIMS: To validate and analyse the scale's psychometric properties in adolescents with Down syndrome. METHODS: A two-stage cross-sectional investigation was conducted. The inventory consists of 60 items that measure 5 dimensions. The test was administered to 644 adolescents with Down syndrome. We carried out exploratory and confirmatory factor analyses. OUTCOMES: The 5-factor structure of the test was confirmed. The internal consistency of four dimensions and the EQ-i:YV's total calculated score yielded high values. CONCLUSIONS: This new version of the EQ-i:YV represents a valid and reliable tool to assess emotional intelligence in Spanish adolescents with Down syndrome.

Inguinal Reconstruction Using Pedicled Rectus Abdominis Flap: A Useful Option for the Application of Radiotherapy.

Given their high rate of complications, radical surgical procedures of anorectal and gynecological tumors require a reliable and individualized reconstruction. The latter is influenced by the frequent indication of adjuvant chemo/radiotherapy that they present. We describe the case of a patient with medical history of vulvar carcinoma that required radical surgery and bilateral inguinal lymphadenectomy. Because of the stage of the tumor, the application of postoperative radiotherapy was clinically indicated; however, after surgery, the patient developed bilateral inguinal ulcers that made postoperative radiotherapy application impossible. Using a radical surgical approach in combination with postoperative radiotherapy increases survival in patients with these types of tumors. Therefore, delaying its use because of wound complications or inadequate reconstruction cannot be justified. The pedicled abdominal rectus flap is an excellent option for this purpose in patients with moderate- to large-sized defects.

Artificial Neural Network to Predict Vine Water Status Spatial Variability Using Multispectral Information Obtained from an Unmanned Aerial Vehicle (UAV).

Water stress, which affects yield and wine quality, is often evaluated using the midday stem water potential (Ψstem). However, this measurement is acquired on a per plant basis and does not account for the assessment of vine water status spatial variability. The use of multispectral cameras mounted on unmanned aerial vehicle (UAV) is capable to capture the variability of vine water stress in a whole field scenario. It has been reported that conventional multispectral indices (CMI) that use information between 500-800 nm, do not accurately predict plant water status since they are not sensitive to water content. The objective of this study was to develop artificial neural network (ANN) models derived from multispectral images to predict the Ψstem spatial variability of a drip-irrigated Carménère vineyard in Talca, Maule Region, Chile. The coefficient of determination (R²) obtained between ANN outputs and ground-truth measurements of Ψstem were between 0.56-0.87, with the best performance observed for the model that included the bands 550, 570, 670, 700 and 800 nm. Validation analysis indicated that the ANN model could estimate Ψstem with a mean absolute error (MAE) of 0.1 MPa, root mean square error (RMSE) of 0.12 MPa, and relative error (RE) of -9.1%. For the validation of the CMI, the MAE, RMSE and RE values were between 0.26-0.27 MPa, 0.32-0.34 MPa and -24.2-25.6%, respectively.

Arthrodesis of the thumb carpometacarpal joint using a quadrangular plate: surgical technique and long-term results of 70 patients.

PURPOSE: To assess the long-term results of trapeziometacarpal arthrodesis using a quadrangular plate, regarding clinical, radiological and functional outcomes, as well as development of complications. MATERIAL AND METHOD: From 2005 to 2015, 70 patients were treated at our institution for primary osteoarthrosis of thumb carpometacarpal joint performing a trapeziometacarpal arthrodesis. A total of 85 arthrodesis were carried out using a titanium quadrangular plate (Proflyle plate, Stryker®, Kalamazoo MI, USA), without grafting in any case. Pre- and postoperative functional data were assessed at the outpatient clinics using DASH, MWS and VAS. All patients were asked for their ability to perform basic daily activities before and after surgery. All patients were also asked about satisfaction and their return to their jobs after surgery. Pre- and postoperative radiological data were also assessed. RESULTS: There were 59 females and 11 males with an average age of 55 years (range 44-60). In 66 cases arthrodesis was carried out in the dominant hand, in 45 cases the right thumb was involved, and in 40 the left thumb was involved; in 15 cases arthrodesis was carried out bilaterally. Preoperative average DASH score was 64 (range 50-85), postoperative average score was 25 (range 5-61). Regarding MWS, 51 patients obtained excellent results, 15 patients obtained good results and 4 patients referred poor results. The preoperative average score of VAS was 6 (range 5-10), which decrease to an average of 2 (range 0-3) after surgery; all those differences were statistically significant. All patients reported a mild loss of motion; however, all of them reported improvement to carry out daily activities. There were four cases of nonunion because of failure of fixation and two cases with dysesthetic scar. There was no development of osteoarthritis in adjacent joints. The average follow-up was 60 months. CONCLUSIONS: The use of quadrangular plates for arthrodesis of the trapeziometacarpal joint is a safety and reproducible technique with a low rate of complications. Arthrodesis decreases pain and improves function in patients with primary osteoarthritis of the thumb carpometacarpal joint; in spite of a mild loss of motion, patients are satisfied with this procedure.

Human COA3 Is an Oligomeric Highly Flexible Protein in Solution.

The assembly of the protein complex of cytochrome c oxidase (COX), which participates in the mitochondrial respiratory chain, requires a large number of accessory proteins (the so-called assembly factors). Human COX assembly factor 3 (hCOA3), also known as MITRAC12 or coiled-coil domain-containing protein 56 (CCDC56), interacts with the first subunit protein of COX to form its catalytic core and promotes its assemblage with the other units. Therefore, hCOA3 is involved in COX biogenesis in humans and can be exploited as a drug target in patients with mitochondrial dysfunctions. However, to be considered a molecular target, its structure and conformational stability must first be elucidated. We have embarked on the description of such features by using spectroscopic and hydrodynamic techniques, in aqueous solution and in the presence of detergents, together with computational methods. Our results show that hCOA3 is an oligomeric protein, forming aggregates of different molecular masses in aqueous solution. Moreover, on the basis of fluorescence and circular dichroism results, the protein has (i) its unique tryptophan partially shielded from solvent and (ii) a relatively high percentage of secondary structure. However, this structure is highly flexible and does not involve hydrogen bonding. Experiments in the presence of detergents suggest a slightly higher content of nonrigid helical structure. Theoretical results, based on studies of the primary structure of the protein, further support the idea that hCOA3 is a disordered protein. We suggest that the flexibility of hCOA3 is crucial for its interaction with other proteins to favor mitochondrial protein translocation and assembly of proteins involved in the respiratory chain.

The number of locking screws predicts the risk of nonunion and reintervention in periprosthetic total knee arthroplasty fractures treated with a nail.

Periprosthetic knee fractures following total knee arthroplasty are increasing proportionally to the number of primary procedures done. We performed a retrospective review of Rorabeck type II fractures treated with a retrograde nail, trying to find the relationship between failure and the number of distal locking screws used. Twenty-six patients were included. The number of distal interlocking screws (patients with one or two distal interlocking screws and patients with three screws) correlated with nonunion (p < 0.1), did not correlate with the malunion rate (p > 0.1) and correlated with the reintervention rate (p < 0.1).

Optical coherence tomography evaluation of late strut coverage patterns between first-generation drug-eluting stents and everolimus-eluting stent.

OBJECTIVES: To compare strut coverage patterns between everolimus-eluting stent (EES) and first-generation drug-eluting stents (DES) at more than 12 months after successful implantation, using optical coherence tomography (OCT). BACKGROUND: No sufficient OCT data has been reported comparing late strut coverage patterns between EES and first-generation DES. The favorable late results after EES implantation could be related to lower rates of uncovered and malapposed struts. METHODS: A total of 66 DES (21 EES, 23 SES, and 22 PES) that were implanted at least 1 year in advance in 40 patients and met good late angiographic results were evaluated by OCT. The percentage of uncovered and malapposed struts, calculated as the ratio of uncovered or malapposed struts to total struts in all cross-sectional images per stent, was compared among the three groups. RESULTS: A total of 35,061 struts were analyzed: 11,967 from EES, 11,855 from SES, and 11m239 from PES. The average tissue coverage thickness of the struts per stent was greater in EES than in SES and PES (109 ± 40 µm vs. 72 ± 27 µm and 83 ± 26 µm, respectively; P = 0.001). The percentage of uncovered struts (1.9 ± 4.1% in EES vs. 11.6 ± 12.7% in SES, P = 0.01 and vs. 7.1 ± 5.2% in PES, P < 0.001) and malapposed struts (0.1 ± 0.3% in EES vs. 1.8 ± 3.5% in SES, P = 0.01 and vs. 3.5 ± 5.1% in PES, P = 0.02) was much lower in EES than in first-generation DES, with no significant differences between SES and PES. CONCLUSIONS: Late strut coverage patterns are not similar between EES and first-generation DES. EES showed a lower percentage of uncovered and malapposed struts.

[Red flags of cardiac amyloidosis in patients with spinal stenosis and yellow ligament hypertrophy]. / «Banderas rojas¼ de amiloidosis cardiaca en pacientes con estenosis de canal lumbar e hipertrofia de ligamento amarillo.

INTRODUCTION: Studies addressing the prevalence of cardiac amyloidosis (CA) among patients with spinal stenosis (SS) are lacking. The identification of the red flags (RF) of CA could lead to early detection of cases of CA. The primary objective of this study was to address the prevalence of RF of CA among patients with SS. METHODS: Transversal study including consecutive cases with SS and yellow ligament hypertrophy (YLH). A clinical assessment that included electrocardiogram, echocardiogram and urine and blood test was performed. A clinical suspicion of CA was defined by the presence of left ventricular hypertrophy plus any RF. RESULTS: One hundred and three patients with SS and YLH were assessed. The prevalence of RF was high: heart failure: 18.4%; aortic stenosis: 1.9%; carpal tunnel syndrome: 7.8%; bicipital tendon rupture: 1.9%; arterial hypotension: 17.4%; polyneuropathy symptoms: 51.5%; pseudoinfarction pattern: 3.9%; low voltages: 15.5%; conduction abnormalities: 15.5%; decreased longitudinal strain: 25.3%; apical sparing pattern: 3.9%. The 57.3% of the cohort met the CA suspicion criteria. CONCLUSION: The prevalence of RF of CA is high among patients with SS and YLH. A high proportion of patients met the CA suspicion criteria.

Molecular pathways in mitochondrial disorders due to a defective mitochondrial protein synthesis.

Mitochondria play a central role in cellular metabolism producing the necessary ATP through oxidative phosphorylation. As a remnant of their prokaryotic past, mitochondria contain their own genome, which encodes 13 subunits of the oxidative phosphorylation system, as well as the tRNAs and rRNAs necessary for their translation in the organelle. Mitochondrial protein synthesis depends on the import of a vast array of nuclear-encoded proteins including the mitochondrial ribosome protein components, translation factors, aminoacyl-tRNA synthetases or assembly factors among others. Cryo-EM studies have improved our understanding of the composition of the mitochondrial ribosome and the factors required for mitochondrial protein synthesis and the advances in next-generation sequencing techniques have allowed for the identification of a growing number of genes involved in mitochondrial pathologies with a defective translation. These disorders are often multisystemic, affecting those tissues with a higher energy demand, and often present with neurodegenerative phenotypes. In this article, we review the known proteins required for mitochondrial translation, the disorders that derive from a defective mitochondrial protein synthesis and the animal models that have been established for their study.

Dysfunction of Drosophila mitochondrial carrier homolog (Mtch) alters apoptosis and disturbs development.

Mitochondrial carrier homologs 1 (MTCH1) and 2 (MTCH2) are orphan members of the mitochondrial transporter family SLC25. Human MTCH1 is also known as presenilin 1-associated protein, PSAP. MTCH2 is a receptor for tBid and is related to lipid metabolism. Both proteins have been recently described as protein insertases of the outer mitochondrial membrane. We have depleted Mtch in Drosophila and show here that mutant flies are unable to complete development, showing an excess of apoptosis during pupation; this observation was confirmed by RNAi in Schneider cells. These findings are contrary to what has been described in humans. We discuss the implications in view of recent reports concerning the function of these proteins.

Targeting cancer stem cell OXPHOS with tailored ruthenium complexes as a new anti-cancer strategy.

BACKGROUND: Previous studies by our group have shown that oxidative phosphorylation (OXPHOS) is the main pathway by which pancreatic cancer stem cells (CSCs) meet their energetic requirements; therefore, OXPHOS represents an Achille's heel of these highly tumorigenic cells. Unfortunately, therapies that target OXPHOS in CSCs are lacking. METHODS: The safety and anti-CSC activity of a ruthenium complex featuring bipyridine and terpyridine ligands and one coordination labile position (Ru1) were evaluated across primary pancreatic cancer cultures and in vivo, using 8 patient-derived xenografts (PDXs). RNAseq analysis followed by mitochondria-specific molecular assays were used to determine the mechanism of action. RESULTS: We show that Ru1 is capable of inhibiting CSC OXPHOS function in vitro, and more importantly, it presents excellent anti-cancer activity, with low toxicity, across a large panel of human pancreatic PDXs, as well as in colorectal cancer and osteosarcoma PDXs. Mechanistic studies suggest that this activity stems from Ru1 binding to the D-loop region of the mitochondrial DNA of CSCs, inhibiting OXPHOS complex-associated transcription, leading to reduced mitochondrial oxygen consumption, membrane potential, and ATP production, all of which are necessary for CSCs, which heavily depend on mitochondrial respiration. CONCLUSIONS: Overall, the coordination complex Ru1 represents not only an exciting new anti-cancer agent, but also a molecular tool to dissect the role of OXPHOS in CSCs. Results indicating that the compound is safe, non-toxic and highly effective in vivo are extremely exciting, and have allowed us to uncover unprecedented mechanistic possibilities to fight different cancer types based on targeting CSC OXPHOS.

Coiled coil domain-containing protein 56 (CCDC56) is a novel mitochondrial protein essential for cytochrome c oxidase function.

In Drosophila melanogaster, the mitochondrial transcription factor B1 (d-mtTFB1) transcript contains in its 5'-untranslated region a conserved upstream open reading frame denoted as CG42630 in FlyBase. We demonstrate that CG42630 encodes a novel protein, the coiled coil domain-containing protein 56 (CCDC56), conserved in metazoans. We show that Drosophila CCDC56 protein localizes to mitochondria and contains 87 amino acids in flies and 106 in humans with the two proteins sharing 42% amino acid identity. We show by rapid amplification of cDNA ends and Northern blotting that Drosophila CCDC56 protein and mtTFB1 are encoded on a bona fide bicistronic transcript. We report the generation and characterization of two ccdc56 knock-out lines in Drosophila carrying the ccdc56(D6) and ccdc56(D11) alleles. Lack of the CCDC56 protein in flies induces a developmental delay and 100% lethality by arrest of larval development at the third instar. ccdc56 knock-out larvae show a significant decrease in the level of fully assembled cytochrome c oxidase (COX) and in its activity, suggesting a defect in complex assembly; the activity of the other oxidative phosphorylation complexes remained either unaffected or increased in the ccdc56 knock-out larvae. The lethal phenotype and the decrease in COX were partially rescued by reintroduction of a wild-type UAS-ccdc56 transgene. These results indicate an important role for CCDC56 in the oxidative phosphorylation system and in particular in COX function required for proper development in D. melanogaster. We propose CCDC56 as a candidate factor required for COX biogenesis/assembly.

Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial.

BACKGROUND: Erlotinib has been shown to improve progression-free survival compared with chemotherapy when given as first-line treatment for Asian patients with non-small-cell lung cancer (NSCLC) with activating EGFR mutations. We aimed to assess the safety and efficacy of erlotinib compared with standard chemotherapy for first-line treatment of European patients with advanced EGFR-mutation positive NSCLC. METHODS: We undertook the open-label, randomised phase 3 EURTAC trial at 42 hospitals in France, Italy, and Spain. Eligible participants were adults (> 18 years) with NSCLC and EGFR mutations (exon 19 deletion or L858R mutation in exon 21) with no history of chemotherapy for metastatic disease (neoadjuvant or adjuvant chemotherapy ending ≥ 6 months before study entry was allowed). We randomly allocated participants (1:1) according to a computer-generated allocation schedule to receive oral erlotinib 150 mg per day or 3 week cycles of standard intravenous chemotherapy of cisplatin 75 mg/m(2) on day 1 plus docetaxel (75 mg/m(2) on day 1) or gemcitabine (1250 mg/m(2) on days 1 and 8). Carboplatin (AUC 6 with docetaxel 75 mg/m(2) or AUC 5 with gemcitabine 1000 mg/m(2)) was allowed in patients unable to have cisplatin. Patients were stratified by EGFR mutation type and Eastern Cooperative Oncology Group performance status (0 vs 1 vs 2). The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. We assessed safety in all patients who received study drug (≥ 1 dose). This study is registered with ClinicalTrials.gov, number NCT00446225. FINDINGS: Between Feb 15, 2007, and Jan 4, 2011, 174 patients with EGFR mutations were enrolled. One patient received treatment before randomisation and was thus withdrawn from the study; of the remaining patients, 86 were randomly assigned to receive erlotinib and 87 to receive standard chemotherapy. The preplanned interim analysis showed that the study met its primary endpoint; enrolment was halted, and full evaluation of the results was recommended. At data cutoff (Jan 26, 2011), median PFS was 9·7 months (95% CI 8·4-12·3) in the erlotinib group, compared with 5·2 months (4·5-5·8) in the standard chemotherapy group (hazard ratio 0·37, 95% CI 0·25-0·54; p < 0·0001). Main grade 3 or 4 toxicities were rash (11 [13%] of 84 patients given erlotinib vs none of 82 patients in the chemotherapy group), neutropenia (none vs 18 [22%]), anaemia (one [1%] vs three [4%]), and increased amino-transferase concentrations (two [2%] vs 0). Five (6%) patients on erlotinib had treatment-related severe adverse events compared with 16 patients (20%) on chemotherapy. One patient in the erlotinib group and two in the standard chemotherapy group died from treatment-related causes. INTERPRETATION: Our findings strengthen the rationale for routine baseline tissue-based assessment of EGFR mutations in patients with NSCLC and for treatment of mutation-positive patients with EGFR tyrosine-kinase inhibitors. FUNDING: Spanish Lung Cancer Group, Roche Farma, Hoffmann-La Roche, and Red Temática de Investigacion Cooperativa en Cancer.

Recommendations of the Spanish Antibiogram Committee (COESANT) for in vitro susceptibility testing of antimicrobial agents by disk diffusion.

Disk diffusion is a well standardized method that provides reliable categorical results to guide antimicrobial therapy in numerous types of infections. Based on the guidelines of the European Committee on Antimicrobial Susceptibility Testing (EUCAST), which are widely implemented in Spain, the Spanish Antibiogram Committee (COESANT) has drawn up recommendations for antimicrobial selection by the disk diffusion technique, including selective reporting and its use for the detection of resistance mechanisms. Factors affecting disk diffusion results, along with advantages and shortcomings of the method, are also discussed.

Spanish Antibiogram Committee (COESANT) recommendations for cumulative antibiogram reports.

The Spanish Antibiogram Committee (Comité Español del Antibiograma, COESANT) presents in this document a series of recommendations intending to unify how cumulative antibiogram reports must be made in Clinical Microbiology Spanish laboratories. This article is based on the information included in the Clinical Microbiology Procedure No. 51, «Preparation of cumulative reports on antimicrobial susceptibility¼ of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), published in 2014. The recommendations also include the modifications in the definition of clinical interpretive categories recently published by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in 2019. Its final objective is to establish a homogeneous way of preparing these summaries to compare results from different centers or aggregate the information from these in order to carry out an adequate local or even national surveillance regarding the evolution of antimicrobial susceptibility.