Ovarian cancer (OC) is a deadly disease that affects a large number of women worldwide. Machine Learning (ML) models can help in the early detection of this disease, however, the use of these models ...may be limited by their lack of interpretability and the difficulty to evaluate their performance. In this work, five types of datasets were used, employing clinical features, different types of coding genomic features, and combining both. The use of interpretable ML (IML) models (one linear and one nonlinear model) provided us with better interpretability of the five feature sets. Following this study, nine binary classification models were compared, and the Accuracy, Recall, and Area Under the Curve were analyzed. The results showed that ML models employed the combination of clinical features and genomes with the coding of the position of genes in patients significantly improves the prediction. We demonstrated that the inclusion of different preprocessed patient data and especially through the information provided by IML models, can help clinicians to understand the disease better and make informed treatment decisions.
Brewers' spent grain (BSG) is a promising agroindustrial waste for the production of biobutanol. One critical point in the butanol production process is the optimization of the enzymatic hydrolysis ...step. In order to obtain the maximum efficiency, it is necessary to use high solids loadings in this process to obtain high concentrations of monosaccharides that allow high titres of butanol to be produced in the ABE fermentation process. The optimum enzyme and solids load maximizing the monosaccharide concentrations and minimizing the phenolic compounds concentrations in the enzymatic hydrolysates from pretreated BSG have been investigated. A dilute sulphuric acid pretreatment was carried out previously to the optimization of the enzymatic hydrolysis. Under optimal conditions (28.1% w/w solids load and 15.4 FPU/g DM), 47.0 g/L of glucose, 16.8 g/L of xylose, and 1.2 g/L of phenolic compounds were attained in the enzymatic hydrolysates. The enzymatic hydrolysates were subjected to an ABE fermentation process (with and without previous detoxification with activated carbon) to evaluate the production of butanol by C. beijerinckii. Maximum global yields of 31.0 g butanol/kg pretreated BSG and 46.4 g ABE/kg pretreated BSG were obtained. The detoxification process had little to no effect on the ABE fermentation process.
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Background: Checkpoint Inhibitors (CPI) have become a new standard of treatment in advanced urothelial carcinoma. However, little is known regarding the outcome of patients in ...daily practice.We aimed to assess tumor response and toxicity of CPIs in a cohort of patients treated in “real world” conditions. In parallel, a comprehensive molecular study in tumor samples from these patients, is ongoing. Methods: We designed an observational retrospective study within the “Grupo Centro” collaborative group. Adult patients diagnosed of metastasic urothelial carcinoma (mUC) and treated with CPIs between 2011-2019 in any of the 20 centers of the group, were eligible. Results: Up to date 100 patients have been included (82% males) with a median age of 74 years (48 -96). In 82% patients primary was bladder cancer. Most common metastasic sites were bone (26%) and liver (16%).With a median follow up of 10,6 months(mo) median progression free survival (mPFS) was 6,6mo (1,4-95,4 range) and median Overall Survival (mOS) was 21.3mo (3,8-121,8). 38% of patients received CPIs in first line(L): atezolizumab:27, pembrolizumab: 10, nivolumab:1. The median number of cycles was 8,2. Up to 51% received platinum-based combinations in first line. 69% (69/100) pts received 2L treatment: 68% with CPIs, 27,5% with chemotherapy and 4% with FGFR inhibitors (as part of a clinical trial). 2L mPFS was 3,5 mo (1,9-25.9). 23% (23/100) patients received 3L, of them 26% (6/23) were treated with CPIs. 3L mPFS:8,3mo(0,4-43,8). As a whole, patients treated with CPI accross different lines, achieved complete response in 8% of the cases, partial response in 18% and stable disease in 15%. Up to 44% of cases presented progressive disease as best response and evaluation was not available in 15%. Most common G1-2 AEs related to immunotherapy were: asthenia:31%,pruritus:16% and anorexia: 9%.10% pts experienced G3-4 toxicity: asthenia G3: 4, diarrhea G3: 1, erythrodysesthesia G3:1, arthromyalgia G3: 1, cardiac arrest G4:1,pneumonitis G4:1,anemia G3:1. Conclusions: This study confirms the efficacy and security of CPIs in real world. Response rates and toxicity profile were comparable to those reported in clinical trials.
BackgroundThe Tumor Microenvironment (TME) has a key role in solid tumor therapy screening. We have developed a 3D ex vivo immunosuppressive assay mimicking the TME. It enables both allogenic & ...autologous tumor lysis by expanded Tumor Infiltrate Lymphocytes (TILs). It is a valuable 3D assay to study the activity of immune therapy drugs in patient sample.MethodsTME-aligned immunosuppressor media was produced by conditioned media from activated human Mesenchymal Stem Cells (hMSC). The TILs were expanded from patient-derived tumor samples and used for tumor killing potential evaluation. Target tumor cells were obtained from different sources: a) Isolated from patient-derived material and frozen until use in experiments with autologous or allogenic TILs or b) Tumor cell lines purchased from ATCC. The cells were mixed according to desired Effector:Target (E:T) ratios and embedded in 3D matrix in presence of TME-aligned media and immune therapy compounds, as Immune Checkpoint inhibitors (ImmChPi). The cell retrieval was performed at the end of desired timepoints and tumor cell killing and TILs activation profile were analyzed by flow cytometry.ResultsThe in vitro expanded TILs were able to kill autologous and allogenic tumor cells in several different E:T ratios within 24 hours. The% tumor cell killing for allogenic samples of the same cancer type showed a similar range as autologous killing. In a representative autologous E:T experiment we observed 40% of killing at E:T ratio 10:1 (figure 1A). These same TILs showed even higher% tumor killing against allogenic tumor samples (up to 90%, data not shown). The Immune Check Point (ImmChP) expression during expansion may change and was followed to select proper expansion timelines. For example, in a particular ovarian cancer sample TIM3 was expressed in 75% of the expanded TILs (figure 1B) and the treatment with TIM3 blocking antibody increased nearly 2-fold tumor cell killing in a dose dependent manner (figure 1C).Abstract 763 Figure 1Autologous killing: novel ex vivo solid tumor 3D assay using autologous TILs from an ovarian cancer patient sample for Immune Check Points or other IO drugs. A) Autologous TILs kill 40% ovarian cancer cells in 24h incubation. B) 75% TILs express TIM3. C) Adding TIM3 antibody enhances killing of tumor cells in a dose dependent manner.ConclusionsThe Novel TME-Aligned 3D IO Assay is a reliable, and powerful tool to study the mode of action of tumor cells lysis by expanded TILs. Immune Therapy Drugs Screening can be performed in autologous or allogenic E:T conditions, allowing full mode of action description of Bi or Multispecific antibodies, ImmChPI and others, and opens a new door for therapy prediction studies in patient‘s material.Ethics ApprovalThe study was approved by Hospital 12 de Octubre Ethics Board, with approval number 14/199.ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.
Ross syndrome is a degenerative disorder characterized by the clinical triad of tonic pupil, hyporeflexia and segmental anhidrosis. Harlequin syndrome is described as segmental anhidrosis without ...ocular sympathetic deficit. Harlequin syndrome exhibits a selective abnormality in the peripheral skin sympathetic nerves and Ross syndrome reveals a widespread autonomic dysfunction.
We present 4 patients with sudomotor dysfunction and different patterns of autonomic abnormalities.
Patients 1 and 2 complained of unilateral facial and upper limb flushing and sweating impairment. Patients 3 and 4 complained of an extensive anhidrosis and compensatory hyperhidrosis, patient 4 also presented an Adie’s pupil. Patients underwent nerve conduction studies, sympathetic skin responses (SSR), cardiovascular reflexes (deep breathing, Valsalva maneuver and standing) and laser evoked potentials.
SSR were absent in the anhidrotic upper limb in patients 1 and 2, either to electric or laser stimuli. No evoked SSR responses were recorded in the four limbs in patients 3 and 4. Patient 4 presented slightly impaired cardiovascular reflexes and patients 2 and 4 presented mild abnormalities in sensory nerve conduction studies. Serologic screening, brain MRI and cervicothoracic CT were normal in all patients. Patients 1 and 2 were affected by a Harlequin syndrome, patient 3 presented an uncompleted Ross syndrome and patient 4 a classic Ross syndrome.
Ross and Harlequin syndrome are two clinically distinguishable expressions of partial dysautonomias belonging to a degenerative autonomic disorder that involves sympathetic, parasympathetic and myelinated nerve fibres with different distribution, extent and degree of impairment.
To evaluate the proficiency of Spanish microbiology laboratories with respect to the antimicrobial susceptibility testing (AST) of Acinetobacter spp.
Eight Acinetobacter spp. with different ...resistance mechanisms were sent to 48 Spanish centres which were asked to report: (i) the AST system used; (ii) MICs; (iii) breakpoints used (CLSI versus EUCAST); (iv) clinical category; and (v) resistance mechanisms inferred. Minor, major and very major errors (mE, ME and VME, respectively) were determined.
The greatest percentages of discrepancies were: (i) by AST method: 18.5% Etest, 14.3% Vitek 2 and Sensititre; (ii) by breakpoints: 20.5% (CLSI) and 10.8% (EUCAST); and (iii) by antimicrobial agent: ampicillin/sulbactam (56.2% CLSI), minocycline (40.7% CLSI), tobramycin (38.7% CLSI, 16.8% EUCAST), imipenem (27.8% CLSI, 30.0% EUCAST) and meropenem (25.4% CLSI, 20.8% EUCAST). Categorical error rates: (i) by AST method ranged from 30.0% (Phoenix) to 100% (Sensititre and disc diffusion) for mE, 0.0% (Etest, Sensititre, disc diffusion) to 40% (Phoenix) for ME, and 0.0% (Sensititre and disc diffusion) to 30% (Phoenix) for VME; (ii) by breakpoints: mE (80.1% CLSI, 58.4% EUCAST), ME (3.5% CLSI, 12.4% EUCAST) and VME (16.4% CLSI, 29.2% EUCAST); and (iii) by antimicrobial agent: mE (100% levofloxacin/CLSI, 100% levofloxacin and meropenem/EUCAST), ME (35.3% colistin/CLSI, 25.0% colistin/EUCAST) and VME (64.7% colistin/CLSI, 86.7% gentamicin/EUCAST).
Clinical microbiology laboratories must improve their ability to determine antimicrobial susceptibilities of Acinetobacter spp. isolates. Higher discrepancies using CLSI when compared with EUCAST are mainly due to mE and to a much lesser extent to ME or VME.
Introduction
SARS-CoV-2 pneumonia is often associated with hyper-inflammation. The cytokine-storm-like is one of the targets of current therapies for coronavirus disease 2019 (COVID-19). High ...Interleukin-6 (IL6) blood levels have been identified in severe COVID-19 disease, but there are still uncertainties regarding the actual role of anti-IL6 antagonists in COVID-19 management. Our hypothesis was that the use of sarilumab plus corticosteroids at an early stage of the hyper-inflammatory syndrome would be beneficial and prevent progression to acute respiratory distress syndrome (ARDS).
Methods
We randomly assigned (in a 1:1 ratio) COVID-19 pneumonia hospitalized patients under standard oxygen therapy and laboratory evidence of hyper-inflammation to receive sarilumab plus usual care (experimental group) or usual care alone (control group). Corticosteroids were given to all patients at a 1 mg/kg/day of methylprednisolone for at least 3 days. The primary outcome was the proportion of patients progressing to severe respiratory failure (defined as a score in the Brescia-COVID19 scale ≥ 3) up to day 15.
Results
A total of 201 patients underwent randomization: 99 patients in the sarilumab group and 102 patients in the control group. The rate of patients progressing to severe respiratory failure (Brescia-COVID scale score ≥ 3) up to day 15 was 16.16% in the Sarilumab group versus 15.69% in the control group (RR 1.03; 95% CI 0.48–2.20). No relevant safety issues were identified.
Conclusions
In hospitalized patients with Covid-19 pneumonia, who were under standard oxygen therapy and who presented analytical inflammatory parameters, an early therapeutic intervention with sarilumab plus standard of care (including corticosteroids) was not shown to be more effective than current standard of care alone. The study was registered at EudraCT with number: 2020-002037-15.
Patients with multimorbidity and complex health needs are defined as a priority by the World Health Organization (WHO) and the European Union. There is a need to develop appropriate strategies with ...effective measures to meet the challenge of chronicity, reorienting national health systems. The increasing expansion of mobile health (mHealth) interventions in patient communication, the reduction of health inequalities, improved access to health care resources, adherence to treatment, and self-care of chronic diseases all point to an optimistic outlook. However, only few mobile apps demonstrate their effectiveness in these patients, which is diminished when they are not based on evidence, or when they are not designed by and for users with different levels of health literacy (HL).
This study aims to evaluate the efficacy of an mHealth intervention relative to routine clinical practice in improving HL and self-management in patients with multimorbidity with heart failure (HF) and complex health needs.
This is a randomized, multicenter, blinded clinical trial evaluating 2 groups, namely, a control group (standard clinical practice) and an intervention group (standard clinical practice and an ad hoc designed mHealth intervention previously developed), for 12 months.
The contents of the mHealth intervention will address user-perceived needs based on the development of user stories regarding diet, physical exercise, cardiac rehabilitation, therapeutic adherence, warning signs and symptoms, and emotional management. These contents have been validated by expert consensus. The creation and development of the contents of the mHealth intervention (app) took 18 months and was completed during 2021. The mobile app is expected to be developed by the end of 2022, after which it will be applied to the experimental group as an adjunct to standard clinical care during 12 months.
The trial will demonstrate whether the mobile app improves HL and self-management in patients with HF and complex health needs, improves therapeutic adherence, and reduces hospital admissions. This study can serve as a starting point for developing other mHealth tools in other pathologies and for their generalization to other contexts.
ClinicalTrials.gov NCT04725526; https://tinyurl.com/bd8va27w.
DERR1-10.2196/35945.
In vitro culture is one of the most studied techniques, and it is used to study many developmental processes, especially in forestry species, because of growth timing and easy manipulation. ...Epigenetics has been shown as an important influence on many research analyses such as cancer in mammals and developmental processes in plants such as flowering, but regarding in vitro culture, techniques to study DNA methylation or chromatin modifications were mainly limited to identify somaclonal variation of the micropropagated material. Because in vitro culture is not only a way to generate plant material but also a bunch of differentially induced developmental processes, an approach of techniques and some research carried out to study the different changes regarding DNA methylation and chromatin and translational modifications that take place during these processes is reviewed.
Background: Pseudomonas aeruginosa healthcare-associated infections are one of the top antimicrobial resistance threats world-wide. In order to analyze the current trends, we performed a Spanish ...nation-wide high-resolution analysis of the susceptibility profiles, the genomic epidemiology and the resistome of P. aeruginosa over a five-year time lapse. Methods: A total of 3.180 nonduplicated P. aeruginosa clinical isolates from two Spanish nation-wide surveys performed in October 2017 and 2022 were analyzed. MICs of 13 antipseudomonals were determined by ISO-EUCAST. Multidrug resistance (MDR)/extensively drug resistance (XDR)/difficult to treat resistance (DTR)/pandrug resistance (PDR) profiles were defined following established criteria. All XDR/DTR isolates were subjected to whole genome sequencing (WGS). Findings: A decrease in resistance to all tested antibiotics, including older and newer antimicrobials, was observed in 2022 vs 2017. Likewise, a major reduction of XDR (15.2% vs 5.9%) and DTR (4.2 vs 2.1%) profiles was evidenced, and even more patent among ICU isolates XDR (26.0% vs 6.0%) and DTR (8.9% vs 2.6%) (p < 0.001). The prevalence of Extended-spectrum β-lactamase/carbapenemase production was slightly lower in 2022 (2.1%. vs 3.1%, p = 0.064). However, there was a significant increase in the proportion of carbapenemase production among carbapenem-resistant strains (29.4% vs 18.1%, p = 0.0246). While ST175 was still the most frequent clone among XDR, a slight reduction in its prevalence was noted (35.9% vs 45.5%, p = 0.106) as opposed to ST235 which increased significantly (24.3% vs 12.3%, p = 0.0062). Interpretation: While the generalized decrease in P. aeruginosa resistance, linked to a major reduction in the prevalence of XDR strains, is encouraging, the negative counterpart is the increase in the proportion of XDR strains producing carbapenemases, associated to the significant advance of the concerning world-wide disseminated hypervirulent high-risk clone ST235. Continued high-resolution surveillance, integrating phenotypic and genomic data, is necessary for understanding resistance trends and analyzing the impact of national plans on antimicrobial resistance. Funding: MSD and the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea—NextGenerationEU.
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