Occult cancer in patients with unprovoked venous thromboembolism: A nested case-control study.

OBJECTIVES: Detecting occult cancer in patients with unprovoked venous thromboembolism (VTE) remains a significant challenge. Our objective was to investigate the potential predictive role of coagulation-related biomarkers in the diagnosis of occult malignancies. METHODS: We conducted a nested case-control study with a 1-year prospective cohort of 214 patients with unprovoked VTE, with a focus on identifying occult cancer. At the time of VTE diagnosis, we measured various biomarkers, including soluble P-selectin (sP-selectin), dimerized plasmin fragment D (D-dimer), platelets, leukocytes, hemoglobin, total extracellular vesicles (EVs), EVs expressing tissue factor on their surface (TF+EVs), and EVs expressing P-selectin on their surface (Psel+EVs) in all participants. RESULTS: We observed statistically significant increased levels of sP-selectin (P = .015) in patients with occult cancer. Despite an increase in Psel+EVs, TF+EVs, D-dimer, and platelets within this group, however, no significant differences were found. When sP-selectin exceeded 62 ng/mL and D-dimer surpassed 10,000 µg/L, the diagnosis of occult cancer demonstrated a specificity of up to 91% (95% CI, 79.9%-96.7%). CONCLUSIONS: The combination of sP-selectin and D-dimer can be a valuable biomarker in detecting occult cancer in patients with unprovoked VTE. Further research is necessary to ascertain whether easily measurable biomarkers such as sP-selectin and D-dimer can effectively distinguish between patients who have VTE with and without hidden malignancies.

Platelet RNA sequencing for cancer screening in patients with unprovoked venous thromboembolism: a prospective cohort study.

BACKGROUND: Platelet RNA sequencing has been shown to accurately detect cancer in previous studies. OBJECTIVES: To compare the diagnostic accuracy of platelet RNA sequencing with standard-of-care limited cancer screening in patients with unprovoked venous thromboembolism (VTE). METHODS: Patients aged ≥40 years with unprovoked VTE were recruited at 13 centers and followed for 12 months for cancer. Participants underwent standard-of-care limited cancer screening, and platelet RNA sequencing analysis was performed centrally at study end for cases and selected controls. Sensitivity and specificity were calculated, using the predefined primary positivity threshold of 0.54 for platelet RNA sequencing aiming at 86% test sensitivity, and an additional predefined threshold of 0.89 aiming at 99% test specificity. RESULTS: A total of 476 participants were enrolled, of whom 25 (5.3%) were diagnosed with cancer during 12-month follow-up. For each cancer patient, 3 cancer-free patients were randomly selected for the analysis. The sensitivity of limited screening was 72% (95% CI, 52-86) at a specificity of 91% (95% CI, 82-95). The area under the receiver operator characteristic for platelet RNA sequencing was 0.54 (95% CI, 0.41-0.66). At the primary positivity threshold, all patients had a positive test, for a sensitivity estimated at 100% (95% CI, 87-99) and a specificity of 8% (95% CI, 3.7-16.4). At the secondary threshold, sensitivity was 68% (95% CI, 48-83; p value compared with limited screening 0.71) at a specificity of 36% (95% CI, 26-47). CONCLUSION: Platelet RNA sequencing had poor diagnostic accuracy for detecting occult cancer in patients with unprovoked VTE with the current algorithm.

Inflammatory response in human lung cells stimulated with plasma from COPD patients.

Background: Chronic obstructive pulmonary disease (COPD) is a condition resulting from a persistent inflammatory state in the airways even after smoking cessation. Intriguingly, the reasons behind this persistence of the inflammatory influx without smoking exposure have not been fully unraveled. We aimed to explore the hypothesis that systemic inflammation in COPD patients influences lung cell inflammatory response. Methods: We cultured human lung fibroblast and human airway epithelial cell lines with plasma from COPD patients (four emphysematous-COPD, four asthma-COPD overlap, four chronic bronchitis-COPD, and four bronchiectasis- COPD), and four smokers or ex-smokers without COPD as controls. Non-stimulated cells were used as controls. We measured Interleukine-8 (IL-8), C-reactive protein (CRP) and matrix metalloproteinase-9 (MMP-9) in plasma and culture supernatants by ELISA. Results: Cells stimulated with plasma from COPD patients and non-COPD smoker subjects produced higher CRP, IL- 8 and MMP-9 levels, an increase for COPD in CRP (p=0.029) in epithelial cells and IL-8 (p=0.039) in fibroblasts and decrease for MMP-9 (p=0.039) in fibroblasts, compared with non-stimulated cells. The response was higher in epithelial cells for IL-8 (p=0.003) and in fibroblasts for MMP-9 (p=0.063). The plasma from chronic bronchitis and bronchiectasis phenotypes induced higher IL-8 in fibroblasts. Conclusions: Plasma from COPD patients increases the inflammatory response in lung epithelial cells and lung fibroblasts, with a different response depending on the cell type and clinical phenotype.

Depression, anxiety, and academic performance in COVID-19: a cross-sectional study.

Depression and anxiety are common after months of social isolation, and they can have a negative impact on anyone's quality of life if they are not treated promptly and appropriately. The aim of this study was to determine if the change to online modality courses and the presence of depression or anxiety symptoms during the COVID-19 pandemic was associated with a difference in the college student's academic achievement. This study was a cross-sectional survey in which we used the Patient Health Questionnaire-9 (PHQ-9) and the General Anxiety Disorder-7 (GAD-7). Also, we examined the students' perceptions of their academic performance using the Academic Self-Concept Scale (ASCS). A total of 610 students responded to the survey. The average score on the Academic Self-Concept Scale was 2.76 ± 0.35, the students presented a risk of 61.5% for possible depressive disorder and 52.1% for possible generalized anxiety disorder. The intensity of depression and anxiety symptoms had a significant effect on Academic Self-Concept Scale scores (p < 0.001 and p < 0.05, respectively). The findings indicate that the COVID-19 pandemic has had a direct effect on students' mental health and academic performance.

Biomarkers of Venous Thromboembolism Recurrence after Discontinuation of Low Molecular Weight Heparin Treatment for Cancer-Associated Thrombosis (HISPALIS-Study).

The most appropriate duration of anticoagulant treatment for cancer-associated venous thromboembolism (CAT) remains unclear. We have conducted a prospective multicenter study in CAT patients with more than 6 months of anticoagulant treatment to predict the risk of venous thromboembolism (VTE) recurrence after anticoagulation discontinuation. Blood samples were obtained when patients stopped the anticoagulation, at 21 days and at 90 days. In each sample we assessed different coagulation-related biomarkers: D-dimer (DD), high-sensitivity C-reactive protein (hs-CRP), P-selectin (PS), phospholipids, soluble tissue factor, factor VIII and the thrombin generation test. It was evaluated 325 CAT patients and 166 patients were included in the study, mean age 64 ± 17 years. VTE recurrence until 6 months after stopping anticoagulation treatment was 9.87% [95% confidence interval (CI): 6−15]. The biomarkers sub-distribution hazard ratios were 6.32 for ratio DD basal/DD 21 days > 2 (95% CI: 1.82−21.90), 6.36 for hs-CRP > 4.5 (95% CI: 1.73−23.40) and 5.58 for PS > 40 (95% CI: 1.46−21.30) after 21 days of stopping anticoagulation. This is the first study that has identified the DD ratio, hs-CRP and PS as potential biomarkers of VTE recurrence in cancer patients after the discontinuation of anticoagulation treatment. A risk-adapted strategy may allow the identification of the optimal time to withdraw the anticoagulation in each CAT patient.

Differences in Postoperative Pain, Nausea, and Vomiting After Elective Laparoscopic Cholecystectomy in Premenopausal and Postmenopausal Mexican Women.

BACKGROUND: Postoperative symptoms and pain after laparoscopic cholecystectomy (LC) are common in women. However, there is no evidence of differences in incidence and severity among different age groups. We evaluated whether adverse postoperative symptoms were more common in younger than in older women after LC. METHODS: One hundred and fifty premenopausal (mean age 37.6 ± 3.6 y) and 145 postmenopausal women (59 ± 5.2 y) were included in this retrospective cohort study. Clinical and anthropometric parameters were analyzed. Study endpoints were the incidences of postoperative nausea and vomiting (PONV) and pain, and the additional analgesics and antiemetics needed after surgery. RESULTS: Body mass index was normal in 42.7% of patients in the younger group and 64.8% in the older group (P < 0.001). Reported pain was more frequent and intense in the younger group throughout the study period (P < 0.01). Additional narcotics were required in 18% of premenopausal versus 7.6% of postmenopausal women (P = 0.001), and the doses used to reduce pain were higher for premenopausal women (P = 0.02). PONV was more frequent in the younger group at 1 and 6 h after surgery (P < 0.005). Rescue antiemetics were required in 29 premenopausal and 13 postmenopausal women (P = 0.01). Hospital stay was shorter for the older patients (P = 0.01). Minor morbidity was observed in both groups (0.7% and 2.1%). There was no mortality. CONCLUSIONS: Early PONV and pain after LC were more frequent in premenopausal women, who also required more rescue analgesic and antiemetic medication.

Nutriepigenomics and chronic obstructive pulmonary disease: potential role of dietary and epigenetics factors in disease development and management.

Over recent decades, a number of studies have revealed the possible role of different types of diets, as well as the nutritional elements they are made up of, in the pathogenesis of chronic obstructive pulmonary disease (COPD). To date, dietary factors have been identified to play a role in the prevention of COPD, with evidence from antioxidant nutrients, vitamins, and fiber intake. Additionally, certain dietary patterns such as the Mediterranean diet, together with other Western diets, provide evidence of the influence on COPD development, promoting lung health through nutritional approaches, and giving us an opportunity for intervention. The effect of diet on COPD is conveyed by 3 mechanisms: regulation of inflammation, oxidative stress, and carbon dioxide produced/oxygen intake. Current advances have begun to highlight the possible role of diet in modifying gene expression in certain individuals that predisposes them to COPD through epigenetic modifications. The relation between dietary intake and epigenetic factors has therefore outlined nutriepigenomics as a possible missing link in the relation between environmental exposure to smoke and the appearance of a subsequent chronic bronchial obstruction. This review summarizes the evidence regarding the influence of dietary patterns and nutrients and epigenetic regulatory mechanisms on COPD development and prevention with the aim of encouraging clinical research on the impact of dietary modifications on COPD-related clinical outcomes. This review highlights the importance of proposing and carrying out future studies focused on the modulating effects of certain nutrients on epigenetic changes in patients with specific COPD phenotypes (bronchiectasis, emphysema, asthma/COPD, chronic bronchitis), and their individual responses to cigarette smoking, environmental pollution, or other noxious particles. The objectives of these future studies must be directed to the development of novel therapeutic approaches and personalized management of COPD.

Interleukin 6 as a marker of depression in women with sleep apnea.

Depression is common in women with obstructive sleep apnea (OSA), but objective markers of depression have not yet been explored in such patients. We hypothesized that inflammation and antioxidant biomarkers may be associated with depression in a cohort of OSA women. We conducted a multicentre, cross-sectional study in 247 women diagnosed with moderate-to-severe OSA. Depression was assessed by the depression subscale of the Hospital Anxiety and Depression Questionnaire (HAD-D) and defined as a score ≥11. Associations between tumour necrosis factor α (TNFα), interleukin 6 (IL-6), C-reactive protein (CRP), intercellular adhesion molecule 1 (ICAM-1), catalase (CAT), superoxide dismutase (SOD) and brain-derived neurotrophic factor (BDNF) plasma levels and depression were assessed. The women had a median (25th-75th percentiles) age of 58 (51-65) years, body mass index (BMI) of 33.5 (29.0-38.3) Kg/m2 , Epworth Sleepiness Scale (ESS) score of 10 (6-13) and apnea-hypopnea index (AHI) of 33.3 (22.8-49.3). Logistic regression analyses revealed that only IL6 levels were associated with the presence of depression (adjusted odds ratio [OR], 1.20; 95% confidence interval [CI], 1.08-1.34), whereas linear regression further confirmed that IL6 levels were significantly associated with HAD-D scores (ß = .154; 95% CI, 0.03-0.30). Multivariate regression analysis showed that IL6 (OR, 1.22; 95% CI, 1.09-1.36), ESS (OR, 1.10; 95% CI 1.02-1.19) and physical activity <30 min/day (OR, 2.51; 95% CI, 1.25-5.05) were independent predictors of depression. Thus, we conclude that in a cohort of women with moderate-to-severe OSA, IL6 levels are independently associated with the presence of depression and correlate with depression scores. Low physical activity and higher ESS scores are also independent indicators of risk of depression in this population.

Association between HEXACO personality traits and medical specialty preferences in Mexican medical students: a cross-sectional survey.

BACKGROUND: Medical specialty is a critical choice in a physician's life because it determines their professional future and medical practice. While some are motivated to choose a specific specialty based on the monetary gain it can provide, others are inspired by seeing the work performed by a physician or by a patient's recovery. It is common to stereotype doctors' personalities by their specialty. METHODS: This was a cross-sectional survey study in which we administered the 100-item HEXACO Personality Inventory-Revised to 292 medical students between September 2018 and March 2019. We evaluated six different domains of personality traits. We also included questions about their medical specialty of choice, their least preferred specialty, and the motivation behind these choices. The participants included 175 women (59.9%) and 117 men (40.1%). RESULTS: When the participants were asked about their preferred type of medical specialty, 52.4% indicated a preference for surgical specialties (surgical group) vs 47.6% who preferred clinical specialties (clinical group). We found that the surgical group showed significantly higher scores for Extraversion and Organization domains, while the clinical group showed significantly higher scores on the Honesty-Humility, Emotionality, and Agreeableness domains. We identified critical differences within the overall group of medical students by their medical specialty preference. CONCLUSIONS: Some classical stereotypes were confirmed by our results, such as surgical specialists tending to be more extroverted and organized, whereas clinical specialists were prone to being more introverted, anxious, and more emotionally attached to their patients.

Evaluation of lung parenchyma, blood vessels, and peripheral blood lymphocytes as a potential source of acute phase reactants in patients with COPD.

Background: Previous studies have shown that the arterial wall is a potential source of inflammatory markers in COPD. Here, we sought to compare the expression of acute phase reactants (APRs) in COPD patients and controls both at the local (pulmonary arteries and lung parenchyma) and systemic (peripheral blood leukocytes and plasma) compartments. Methods: Consecutive patients undergoing elective surgery for suspected primary lung cancer were eligible for the study. Patients were categorized either as COPD or control group based on the spirometry results. Pulmonary arteries and lung parenchyma sections, peripheral blood leukocytes, and plasma samples were obtained from all participants. Gene expression levels of C-reactive protein (CRP) and serum amyloid A (SAA1, SAA2, and SAA4) were evaluated in tissue samples and peripheral blood leukocytes by reverse transciption-PCR. Plasma CRP and SAA protein levels were measured by enzyme-linked immunosorbent assays. Proteins were evaluated in paraffin-embedded lung tissues by immunohistochemistry. Results: A total of 40 patients with COPD and 62 controls were enrolled. We did not find significant differences in the gene expression between COPD and control group. Both CRP and SAA were overexpressed in the lung parenchyma compared with pulmonary arteries and peripheral blood leukocytes. The expression of SAA was significantly higher in the lung parenchyma than in the pulmonary artery (2-fold higher for SAA1 and SAA4, P=0.015 and P<0.001, respectively; 8-fold higher for SAA2, P<0.001) and peripheral blood leukocytes (16-fold higher for SAA1, 439-fold higher for SAA2, and 5-fold higher for SAA4; P<0.001). No correlation between plasma levels of inflammatory markers and their expression in the lung and peripheral blood leukocytes was observed. Conclusions: The expression of SAA in lung parenchyma is higher than in pulmonary artery and peripheral blood leukocytes. Notably, no associations were noted between lung expression of APRs and their circulating plasma levels, making the leakage of inflammatory proteins from the lung to the bloodstream unlikely. Based on these results, other potential sources of systemic inflammation in COPD (eg, the liver) need further scrutiny.

Effect of continuous positive airway pressure on inflammatory, antioxidant, and depression biomarkers in women with obstructive sleep apnea: a randomized controlled trial.

STUDY OBJECTIVES: The effect of continuous positive airway pressure (CPAP) on mediators of cardiovascular disease and depression in women with obstructive sleep apnea (OSA) is unknown. We aimed to assess the effect of CPAP therapy on a variety of biomarkers of inflammation, antioxidant activity, and depression in women with OSA. METHODS: We conducted a multicenter, randomized controlled trial in 247 women diagnosed with moderate-to-severe OSA (apnea-hypopnea index [AHI] ≥ 15). Women were randomized to CPAP (n = 120) or conservative treatment (n = 127) for 12 weeks. Changes in tumor necrosis factor α (TNFα), interleukin 6 (IL-6), C-reactive protein (CRP), intercellular adhesion molecule 1 (ICAM-1), catalase (CAT), superoxide dismutase (SOD), and brain-derived neurotrophic factor (BDNF) were assessed. Additional analyses were conducted in subgroups of clinical interest. RESULTS: Women had a median (25th-75th percentiles) age of 58 (51-65) years, body mass index 33.5 (29.0-38.3) kg/m2, and AHI 33.3 (22.8-49.3). No differences were found between groups in the baseline levels of the biomarkers. After 12 weeks of follow-up, there were no changes between groups in any of the biomarkers assessed. These results did not change when the analyses were restricted to sleepy women or to those with severe OSA. In women with CPAP use at least 5 hours per night, only TNFα levels decreased compared to the control group (-0.29 ± 1.1 vs -0.06 ± 0.53, intergroup difference -0.23 [95% CI = -0.03 to -0.50]; p = 0.043). CONCLUSIONS: Twelve weeks of CPAP therapy does not improve biomarkers of inflammation, antioxidant activity, or depression compared to conservative treatment in women with moderate-to-severe OSA. TRIAL REGISTRATION: NCT02047071.

Factores predictores de trombosis en pacientes con cáncer / Prognostic Factors for Thrombosis in Cancer Patients

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D-dimer and high-sensitivity C-reactive protein levels to predict venous thromboembolism recurrence after discontinuation of anticoagulation for cancer-associated thrombosis.

BACKGROUND: Optimal duration of anticoagulation for cancer-associated thrombosis (CAT) remains unclear. This study assessed D-dimer (DD) and high-sensitivity C-reactive protein (hs-CRP) levels after the withdrawal of anticoagulation treatment to predict the risk of venous thromboembolism (VTE) recurrence among patients with CAT. METHODS: Prospective, multicentre study to evaluate CAT with ≥3 months of anticoagulation that was subsequently discontinued. Blood samples were taken when patients stopped the anticoagulation and 21 days later to determine the DD and hs-CRP levels. All patients were followed up for 6 months to detect VTE recurrence. RESULTS: Between 2013 and 2015, 325 patients were evaluated and 114 patients were ultimately enrolled in the study. The mean age was 62 ± 14 years and nearly 40% had metastasis. Ten patients developed VTE recurrence within 6 months (8.8%, 95% confidence interval [CI]: 4.3-15.5%). The DD and hs-CRP levels after 21 days were associated with VTE recurrence. The subdistribution hazard ratios were 9.82 for hs-CRP (95% CI: 19-52) and 5.81 for DD (95% CI: 1.1-31.7). CONCLUSIONS: This study identified that hs-CRP and DD were potential biomarkers of VTE recurrence after discontinuation of anticoagulation in CAT. A risk-adapted strategy could identify low-risk patients who may benefit from discontinuation of anticoagulation.

Papel de los polimorfismos de la GST (Glutation-S-transferasa) en la susceptibilidad genética a desarrollar asma bronquial en una población de asmáticos andaluces / The role of GST (Glutathione S-transferases) polymorphisms in the genetic susceptibility to develop bronchial asthma in a population of andalusian asthmatics

OBJETIVO: Analizar la presencia de variaciones genéticas en las enzimas de detoxificación GST (Glutation-S-transferasa), concretamente las enzimas GSTM1, GSTT1 y GSTP1.5, en pacientes con asma bronquial y la posible asociación con parámetros clínicos, funcionales e inflamatorios. METODOLOGÍA: Se incluyeron pacientes en seguimiento por asma bronquial junto a un grupo control de individuos no asmáticos. Se analizaron, junto al análisis genético, los parámetros clínicos, incluido ACT, grado de gravedad y grado de control, parámetros funcionales y de inflamación (FeNO-Fracción espirada de óxido nítrico). El estudio genético se realizó mediante extracción del ADN celular de sangre periférica y su posterior análisis por técnicas de biología molecular (PCR: reacción en cadena de la polimerasa y electroforesis en geles de agarosa) en el Instituto de Biomedicina de Sevilla (IBIS). RESULTADOS: Se estudiaron 256 asmáticos, y un grupo control de 40 pacientes. El mayor porcentaje de pacientes presentaban un asma moderada (53%), frente al 23% de asma leve y 24% de asma grave. Según el grado de control en el momento de la inclusión, presentaban buen control el 46% de la serie, mal control el 30% y un 24% de los pacientes estaban parcialmente controlados. En cuanto a la presencia de los polimorfismos: el polimorfismo GSTM1 presentaba genotipo positivo (sin delección) en el 34% de la serie, frente al 65,9% que presentaban genotipo nulo (deleccionadoausencia de la enzima de depuración); en el caso del polimorfismo GSTT1, el 75,6% presentaban genotipo positivo y 24,4% genotipo nulo. De las tres posibilidades polimórficas del GSTP1.5 (34% presentaban genotipo A/A; 48,8% genotipo A/G y 17,1% genotipo G/G). Encontramos un asociación estadísticamente significativa (p = 0,017) entre la presencia del alelo Ile/Ile (A/A) del polimorfismo GSTP1.5 y las mujeres asmáticas, así como con niveles más bajos de FeNO. CONCLUSIONES: no encontramos diferencias estadísticamente significativas entre la presencia de los polimorfismos GSTM1, GSTT1 con ninguno de los parámetros clínicos y funcionales analizados. En cuanto a la presencia del polimorfismo GSTP1.5, encontramos relación estadísticamente significativa con la presencia de asma bronquial en la población de mujeres, concretamente con la presencia del genotipo A/A homocigoto y que a su vez presentaba valores más bajos de FeNO

OBJECTIVE: to analyze the presence of genetic variations in the GST (glutathione S-transferase) detoxification enzymes, specifically the GSTM1, GSTT1 and GSTP1.5 enzymes, in patients with bronchial asthma and their possible association with clinical, functional and inflammatory parameters. METHODS: Patients undergoing follow-up for bronchial asthma were included along with a control group of non-asthmatic individuals. In addition to genetic analysis, the clinical parameters including ACT, degree of severity and degree of control, and functional and inflammation parameters (FeNO, fractional exhaled nitric oxide) were analyzed. The genetic study was done by extracting cellular DNA from peripheral blood which was then analyzed using molecular biology techniques (PCR: polymerase chain reaction and agarose gel electrophoresis) at the Instituto de Biomedicina de Sevilla (IBIS). RESULTS: 256 asthmatic patients and a control group of 40 patients were studied. The majority of patients presented with moderate asthma (53%), compared to 23% with mild asthma and 24% with severe asthma. According to degree of control upon inclusion, 46% of patients in the series had good control, 30% poor control, and 24% of patients were partially controlled. With regard to the presence of polymorphisms: the GSTM1 polymorphism showed a positive genotype (without deletion) in 34% of patients in the series, compared to 65.9% who showed a null genotype (deleted-absent purification enzyme); as for the GSTT1 polymorphism, 75.6% of patients showed a positive genotype and 24.4% a null genotype. Of the three polymorphic possibilities for GSTP1.5, 34% showed the AA genotype, 48.8% the AG genotype and 17.1% the GG genotype. We found a statistically significant association (p = 0.017) between the Ile/ Ile (AA) allele of the GSTP1.5 polymorphism and asthmatic women, as well as lower FeNO levels. CONCLUSIONS: We did not find statistically significant differences between the presence of the GSTM1 and GSTT1 polymorphisms and any of the analyzed clinical or functional parameters. With regard to the presence of the GSTP1.5 polymorphism, we found a statistically significant relationship with the presence of bronchial asthma in the female population, specifically with the presence of the homozygous AA genotype and the fact they also showed lower FeNO values