Case-Control Analysis of the Impact of Anemia on Quality of Life in Patients with Cancer: A Qca Study Analysis

The impact of anemia on the quality of life (QoL) in cancer patients has been studied previously; however, the cut-off point used to define anemia differed among studies, thus providing inconsistent results. Therefore, we analysed the clinical impact of anemia on QoL using the same cut-off point for hemoglobin level to define anemia as that used in ESMO clinical practice guidelines. This post-hoc analysis aimed to determine the impact of anemia on QoL in cancer patients through the European Organization for Research and Treatment of Cancer Quality of life questionnaire version 3.0 (EORTC QLQ-C30) and Euro QoL 5-dimension 3-level (EQ-5D-3L) questionnaire. We found that cancer patients with anemia had significantly worse QoL in clinical terms. In addition, anemic patients had more pronounced symptoms than those in non-anemic patients. Anemia is a common condition in cancer patients and is associated with a wide variety of symptoms that impair quality of life (QoL). However, exactly how anemia affects QoL in cancer patients is unclear because of the inconsistencies in its definition in previous reports. We aimed to examine the clinical impact of anemia on the QoL of cancer patients using specific questionnaires. We performed a post-hoc analysis of a multicenter, prospective, case-control study. We included patients with cancer with (cases) or without (controls) anemia. Participants completed the European Organization for Research and Treatment of Cancer Quality of Life questionnaire version 3.0 (EORTC QLQ-C30) and Euro QoL 5-dimension 3-level (EQ-5D-3L) questionnaire. Statistically significant and clinically relevant differences in the global health status were examined. From 2015 to 2018, 365 patients were included (90 cases and 275 controls). We found minimally important differences in global health status according to the EORTC QLQ-C30 questionnaire (case vs. controls: 45.6 vs. 58%, respectively; mean difference: -12.4, p < 0.001). Regarding symptoms, cancer patients with anemia had more pronounced symptoms in six out of nine scales in comparison with those without anemia. In conclusion, cancer patients with anemia had a worse QoL both clinically and statistically

Searching molecular biomarkers correlating with BSID-III at 24 months in infants with neonatal hypoxic-ischemic encephalopathy

An early prediction of outcomes of neonatal hypoxic-ischemic encephalopathy (NE) is of key importance in reducing neonatal mortality and morbidity. The objectives were (i) to analyze the characteristics of miRNA expression and metabolic patterns of neonates with NE and (ii) to assess their predictive performance for neurodevelopmental outcomes. Plasma samples from moderate/severe NE patients (N = 92) of the HYPOTOP study were collected before, during, and after therapeutic hypothermia (TH) and compared to a control group (healthy term infants). The expression of miRNAs and concentrations of metabolites (hypoxia-related and energy, steroid, and tryptophan metabolisms) were analyzed. Neurodevelopmental outcomes were evaluated at 24 months postnatal age using Bayley Scales of Infant Development, ed. III, BSID-III. Differences in miRNA and metabolic profiles were found between NE vs. control infants, abnormal (i.e., mildly and moderately abnormal and severe) vs. normal, and severe vs. non-severe (i.e., normal and mildly and moderately abnormal) BSID-III. 4-Androstene-3,17-dione, testosterone, betaine, xanthine, and lactate were suitable for BSID-III outcome prediction (receiver operating characteristic areas under the curve (AUCs) ≥ 0.6), as well as 68 miRNAs (AUCs of 0.5–0.9). Significant partial correlations of xanthine and betaine levels and the expression of several miRNAs with BSID-III sub-scales were found. Conclusion: We have identified metabolites/miRNAs that might be useful to support the prediction of middle-term neurodevelopmental outcomes of NE.This study has been funded by Instituto de Salud Carlos III (ISCIII) through the project “RD21/0012/0015” and co-funded by the European Union—NextGenerationEU

Clustering COVID-19 ARDS patients through the first days of ICU admission. An analysis of the CIBERESUCICOVID Cohort

Background Acute respiratory distress syndrome (ARDS) can be classified into sub-phenotypes according to different inflammatory/clinical status. Prognostic enrichment was achieved by grouping patients into hypoinflammatory or hyperinflammatory sub-phenotypes, even though the time of analysis may change the classification according to treatment response or disease evolution. We aimed to evaluate when patients can be clustered in more than 1 group, and how they may change the clustering of patients using data of baseline or day 3, and the prognosis of patients according to their evolution by changing or not the cluster.Methods Multicenter, observational prospective, and retrospective study of patients admitted due to ARDS related to COVID-19 infection in Spain. Patients were grouped according to a clustering mixed-type data algorithm (k-prototypes) using continuous and categorical readily available variables at baseline and day 3.Results Of 6205 patients, 3743 (60%) were included in the study. According to silhouette analysis, patients were grouped in two clusters. At baseline, 1402 (37%) patients were included in cluster 1 and 2341(63%) in cluster 2. On day 3, 1557(42%) patients were included in cluster 1 and 2086 (57%) in cluster 2. The patients included in cluster 2 were older and more frequently hypertensive and had a higher prevalence of shock, organ dysfunction, inflammatory biomarkers, and worst respiratory indexes at both time points. The 90-day mortality was higher in cluster 2 at both clustering processes (43.8% [n = 1025] versus 27.3% [n = 383] at baseline, and 49% [n = 1023] versus 20.6% [n = 321] on day 3). Four hundred and fifty-eight (33%) patients clustered in the first group were clustered in the second group on day 3. In contrast, 638 (27%) patients clustered in the second group were clustered in the first group on day 3.Conclusions During the first days, patients can be clustered into two groups and the process of clustering patients may change as they continue to evolve. This means that despite a vast majority of patients remaining in the same cluster, a minority reaching 33% of patients analyzed may be re-categorized into different clusters based on their progress. Such changes can significantly impact their prognosis

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Análisis estadístico de datos textuales. Aplicación al estudio de las declaraciones del Libertador Simón Bolívar

En este trabajo se presenta una estrategia metodológica basada en el Análisis Estadístico de Datos Textuales de corpus cronológicos. Se emplean distintas herramientas tales como: los métodos estadísticos multidimensionales descriptivos y métodos derivados de la estadística léxica. La utilización del Análisis Estadístico de Datos Textuales permite, entre otras posibilidades, una lectura de los textos sustancialmente distinta y complementaria a las lecturas realizadas desde un enfoque más cualitativo. Consideramos que esta aplicación es novedosa ya que la misma ha sido escasamente empleada para tratar declaraciones e inferir las concepciones mentales de los sujetos y analizar cambios evolutivos

A case-control analysis of the impact of venous thromboembolic disease on quality of life of patients with cancer: Quality of life in cancer (Qca) study

Although there is published research on the impact of venous thromboembolism (VTE) on quality of life (QoL), this issue has not been thoroughly investigated in patients with cancer—particularly using specific questionnaires. We aimed to examine the impact of acute symptomatic VTE on QoL of patients with malignancies. This was a multicenter, prospective, case-control study conducted in patients with cancer either with (cases) or without (controls) acute symptomatic VTE. Participants completed the EORTC QLQ-C30, EQ-5D-3L, PEmb-QoL, and VEINES-QOL/Sym questionnaires. Statistically significant and clinically relevant differences in terms of global health status were examined. Between 2015 and 2018, we enrolled 425 patients (128 cases and 297 controls; mean age: 60.2 ± 18.4 years). The most common malignancies were gastrointestinal (23.5%) and lung (19.8%) tumors. We found minimally important differences in global health status on the EQ-5D-3L (cases versus controls: 0.55 versus 0.77; mean difference: −0.22) and EORTC QLQ-C30 (47.7 versus 58.4; mean difference: −10.3) questionnaires. There were minimally important differences on the PEmb-QoL questionnaire (44.4 versus 23; mean difference: −21.4) and a significantly worse QoL on the VEINES-QOL/Sym questionnaire (42.7 versus 51.7; mean difference: −9). In conclusion, we showed that acute symptomatic VTE adversely affects the QoL of patients with malignancies.This project was financially supported by Leo Pharma (6/2013) and Neumosur (9/2014)

Association between histological diaphragm atrophy and ultrasound diaphragm expiratory thickness in ventilated patients

Background: Diaphragm fiber atrophy has been evidenced after short periods of mechanical ventilation (MV) and related to critical illness-associated diaphragm weakness. Atrophy is described as a decrease in diaphragm fiber cross-sectional area (CSA) in human diaphragm biopsy, but human samples are still difficult to obtain in clinics. In recent years, ultrasound has become a useful tool in intensive care to evaluate diaphragm anatomy. The present study aimed to evaluate the ability of diaphragm expiratory thickness (Tdi) measured by ultrasound to predict diaphragm atrophy, defined by a decrease in diaphragm fiber CSA obtained through diaphragm biopsy (the gold standard technique) in ventilated patients. Methods: Diaphragm biopsies and diaphragm ultrasound were performed in ventilated donors and in control subjects. Demographic variables, comorbidities, severity on admission, treatment, laboratory test results and evolution variables were evaluated. Immunohistochemical analysis to determine CSA and ultrasound measurements of Tdi at end-expiration were performed, and median values of the control group were used as thresholds to determine agreement between them in further analysis. Sensitivity, specificity, and positive and negative predictive values of an ultrasound Tdi cutoff for detecting histologic atrophy were calculated. Agreement between two ultrasound observers was also assessed. Results: Thirty-five ventilated organ donors and 5 ventilated controls were included, without differences in basic characteristics. CSA and Tdi were lower in donors than in controls. All donors presented lower CSA, but only 74% lower Tdi regarding control group thresholds. The cut-off value for lower diaphragm expiratory thickness (Tdi < 1.7 mm) presented a sensitivity of 73%, a specificity of 67%, a positive predictive value of 96% and a negative predictive value of 17% for determining the presence of diaphragm atrophy (CSA < 2851 μm2). Conclusions: Diaphragm atrophy and thickness reduction is associated to MV. While a lower Tdi in diaphragm ultrasound is a good tool for diagnosing atrophy, normal or increased Tdi cannot rule atrophy out showing that both parameters should not be considered as synonymous

Structural differences in the diaphragm of patients following controlled vs assisted and spontaneous mechanical ventilation

Purpose: Ventilator-induced diaphragm dysfunction or damage (VIDD) is highly prevalent in patients under mechanical ventilation (MV), but its analysis is limited by the difficulty of obtaining histological samples. In this study we compared diaphragm histological characteristics in Maastricht III (MSIII) and brain-dead (BD) organ donors and in control subjects undergoing thoracic surgery (CTL) after a period of either controlled or spontaneous MV (CMV or SMV). Methods: In this prospective study, biopsies were obtained from diaphragm and quadriceps. Demographic variables, comorbidities, severity on admission, treatment, and ventilatory variables were evaluated. Immunohistochemical analysis (fiber size and type percentages) and quantification of abnormal fibers (a surrogate of muscle damage) were performed. Results: Muscle samples were obtained from 35 patients. MSIII (n = 16) had more hours on MV (either CMV or SMV) than BD (n = 14) and also spent more hours and a greater percentage of time with diaphragm stimuli (time in assisted and spontaneous modalities). Cross-sectional area (CSA) was significantly reduced in the diaphragm and quadriceps in both groups in comparison with CTL (n = 5). Quadriceps CSA was significantly decreased in MSIII compared to BD but there were no differences in the diaphragm CSA between the two groups. Those MSIII who spent 100 h or more without diaphragm stimuli presented reduced diaphragm CSA without changes in their quadriceps CSA. The proportion of internal nuclei in MSIII diaphragms tended to be higher than in BD diaphragms, and their proportion of lipofuscin deposits tended to be lower, though there were no differences in the quadriceps fiber evaluation. Conclusions: This study provides the first evidence in humans regarding the effects of different modes of MV (controlled, assisted, and spontaneous) on diaphragm myofiber damage, and shows that diaphragm inactivity during mechanical ventilation is associated with the development of VIDD

Non-invasive oxygenation support in acutely hypoxemic COVID-19 patients admitted to the ICU : a multicenter observational retrospective study

Background: Non-invasive oxygenation strategies have a prominent role in the treatment of acute hypoxemic respiratory failure during the coronavirus disease 2019 (COVID-19). While the efficacy of these therapies has been studied in hospitalized patients with COVID-19, the clinical outcomes associated with oxygen masks, high-flow oxygen therapy by nasal cannula and non-invasive mechanical ventilation in critically ill intensive care unit (ICU) patients remain unclear. Methods: In this retrospective study, we used the best of nine covariate balancing algorithms on all baseline covariates in critically ill COVID-19 patients supported with > 10 L of supplemental oxygen at one of the 26 participating ICUs in Catalonia, Spain, between March 14 and April 15, 2020. Results: Of the 1093 non-invasively oxygenated patients at ICU admission treated with one of the three stand-alone non-invasive oxygenation strategies, 897 (82%) required endotracheal intubation and 310 (28%) died during the ICU stay. High-flow oxygen therapy by nasal cannula (n = 439) and non-invasive mechanical ventilation (n = 101) were associated with a lower rate of endotracheal intubation (70% and 88%, respectively) than oxygen masks (n = 553 and 91% intubated), p < 0.001. Compared to oxygen masks, high-flow oxygen therapy by nasal cannula was associated with lower ICU mortality (hazard ratio 0.75 [95% CI 0.58-0.98), and the hazard ratio for ICU mortality was 1.21 [95% CI 0.80-1.83] for non-invasive mechanical ventilation. Conclusion: In critically ill COVID-19 ICU patients and, in the absence of conclusive data, high-flow oxygen therapy by nasal cannula may be the approach of choice as the primary non-invasive oxygenation support strategy