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OBJECTIVE: Add-on therapy with monoclonal antibodies is the recommended therapy for severe asthmatic patients refractory to maintenance treatment. In randomized control trials, mepolizumab reduced the number of exacerbations, the need of oral corticosteroids (OCS), increased asthma control, and lung function in a population of uncontrolled severe eosinophilic asthmatic patients. In this piece of work, we aimed to assess mepolizumab efficacy and safety in a cohort of patients with severe eosinophilic asthma in real-life conditions. METHODS: A retrospective study was carried out at eight hospitals from Asturias (Spain). The sample included patients treated with mepolizumab from 1 January 2016 to 31 March 2019. Demographic and clinical variables were collected, including OCS use, asthma control, lung function, and exacerbation rate. RESULTS: Sixty-nine patients (72% women) with mean age 56 ± 13 years were included. Annual exacerbation rate decreased from 4.7 (SD 3.7) to 1.3 (SD 2.5) (p < 0.001). The number of patients requiring OCS treatment decreased from 25 patients (36%, mean prednisone dose = 18 mg/day) to 13 patients (19%, mean prednisone dose = 9 mg/day) (p < 0.001). Twelve patients (48%) stopped OCS treatment. Forced expired volume in one second (FEV1) as percentage increased from 68% (SD 20) to 76% (SD 21) (p < 0.001). Fifty-six patients (81%) were considered responders to mepolizumab. No serious adverse events were detected during the study period. CONCLUSIONS: Overall, this study demonstrates mepolizumab efficacy and safety in a cohort of patients with uncontrolled severe eosinophilic asthma in routine clinical practice.
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Antiasmáticos , Asma , Eosinofilia Pulmonar , Corticoesteroides/uso terapéutico , Adulto , Anciano , Antiasmáticos/efectos adversos , Anticuerpos Monoclonales Humanizados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prednisona/uso terapéutico , Eosinofilia Pulmonar/inducido químicamente , Eosinofilia Pulmonar/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
OBJECTIVE: To analyse the accuracy of commonly used risk scores (PSI and CURB-65) in predicting mortality and need for ICU admission in Covid-19. MATERIAL AND METHODS: Prospective study of patients diagnosed with Covid-19 pneumonia. Patients were followed until home discharge or death. PSI, CURB-65, SMART-COP and MuLBSTA severity scores were assessed on admission. Risk scores were related to mortality and ICU admission. RESULTS: About 249 patients, 143 males (57.4%) were included. The mean age was 65.6 + 16.1 years. Factors associates with mortality in the multivariate analysis were age > 80 years (OR: 13.9; 95% CI 3.8-51.1) (P = .000), lymphocytes < 800 (OR: 2.9; CI 95% 1.1-7-9) (P = .040), confusion (OR: 6.3; 95% CI 1.6-24.7) (P = .008) and NT-proBNP > 500 pg/mL (OR: 10.1; 95% CI 1.1-63.1) (P = .039). In predicting mortality, the PSI score: AUC 0.874 (95% CI 0.808-0.939) and the CURB-65 score: AUC 0.852 (95% CI 0.794-0.909) were the ones that obtained the best results. In the need for ICU admission, the SMART-COP score: AUC 0.749 (95% CI 0.695-0.820) and the MuLBSTA score: AUC 0.777 (95% CI 0.713-0.840) were the ones that obtained better results, with significant differences with PSI and CURB-65. The scores with the lowest value for ICU admission prediction were PSI with AUC of 0.620 (95% CI 0.549-0.690) and CURB-65 with AUC of 0.604 (95% CI 0.528-0.680). CONCLUSIONS: Prognosis scores routinely used for CAP (PSI and CURB-65) were good predictors for mortality in patients with Covid-19 CAP but not for need of hospitalisation or ICU admission. In the evaluation of Covid-19 pneumonia, we need scores that allow to decide the appropriate level of care.
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COVID-19 , Infecciones Comunitarias Adquiridas , Neumonía , Anciano , Anciano de 80 o más Años , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , SARS-CoV-2 , Índice de Severidad de la EnfermedadRESUMEN
Objective: The aim of our study was to determine the tomographic findings and prevalence of bronchiectasis in our population of patients with severe asthma, and to identify factors associated with the presence of bronchiectasis in these patients. Materials and methods: We retrospectively collected data from the medical histories of patients referred to the asthma unit of our hospital, with a diagnosis of severe asthma between 2015 and 2017. Patients with ABPA, cystic fibrosis, immunodeficiency or systemic disease were excluded. High-resolution thorax-computed tomodensitography (HRCT) was performed in all patients. A standardized protocol was applied in data collection. Results: A total of 108 patients comprising 50 men (46%) and 58 women (54%) were included in the study. Of the 108 patients, 59 (55%) had at least one abnormality detected by HRCT, the most commonly reported abnormalities being bronchiectasis (35%), bronchial wall thickening (33%), emphysema (7%), atelectasis area (6%), mosaic attenuation due to air trapping (4%), and "tree in bud" image (2%). Subjects with bronchiectasis were older (p = 0.001), had a longer asthma history (p = 0.048), had poorer pulmonary function tests with lower FVC (p = 0.031), had more severe bronchial obstruction with lower FEV1 (p = 0.008) and had lower FEV1/FVC (p = 0.003). They also experienced more frequent hospitalizations in the previous year (p = 0.019) and received treatment with omalizumab more frequently (p = 0.049). Plasma eosinophil count and IgE levels were comparable in both groups. In the multivariate analysis, the presence of bronchiectasis was associated with ages older than 40 (OR: 8.3; 95% CI: 1.7-41.2) and chronic airflow obstruction (OR: 5.4; 95% CI: 1.9-15.3). Conclusions: We found that in patients with severe asthma, the prevalence of bronchiectasis is high and that bronchiectasis is associated with a longer asthma history, greater severity and, more importantly, chronic airflow obstruction. These findings are still insufficient evidence to considere features of asthma-bronchiectasis overlap syndrome, a distinct phenotype of severe asthma, but bronchiectasis is a frequent phenomenon leading to a more severe disease with frequent exacerbations. The performance of thorax HRCT on patients with severe asthma can help to evaluate management strategies for the disease in order to improve treatment and prognosis.
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Asma/epidemiología , Bronquiectasia/epidemiología , Adulto , Anciano , Asma/diagnóstico por imagen , Bronquiectasia/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Tórax/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
INTRODUCTION: Poor sleep quality and excessive daytime sleepiness are common in patients with cystic fibrosis (CF), and both are negatively correlated with health-related quality of life (HRQoL). The objective of our study was to evaluate subjective and objective sleep quality in adult CF patients and its effect on HRQoL. MATERIALS AND METHODS: This was a descriptive, prospective, cross-sectional study of CF patients > 18 years of age. Patients underwent nocturnal polysomnography (PSG) and were administered the Pittsburgh Sleep Quality Index questionnaire (PSQI) and the Cystic Fibrosis Quality of Life Questionnaire (CFQR 14 + Spain). RESULTS: The study included 23 patients, 14 women (61%). The mean age of the participants was 32 + 18 years. The mean PSQI score was 5.57 + 3.55; 13 (56.5%) of the patients were poor sleepers, and 13% reported poor sleep quality; seven (30%) had sleep latency > 30 min, 10 (43.5%) had sleep efficiency < 85%. Nineteen underwent polysomnography. According to PSG measurements, sleep efficiency was less than 90% in 61% of the patients. Pathological values were found for the following parameters: intra-sleep wakefulness in 12 patients (63%); microarousal index in 12 patients (63%); and apnea-hypopnea index (AHI) in 2 patients. The desaturation time with SpO2 < 90% (T90) was > 30% in 3 patients. We observed a significant correlation between PSQI and all dimensions of CFQR 14. CONCLUSIONS: Subjective and objective sleep efficiency decreases in adult CF patients. Sleep quality has an impact on HRQoL. The PSQI questionnaire was able to discriminate sleep quality.
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Fibrosis Quística/fisiopatología , Calidad de Vida , Trastornos Intrínsecos del Sueño/fisiopatología , Latencia del Sueño , Adolescente , Adulto , Estudios Transversales , Fibrosis Quística/complicaciones , Femenino , Humanos , Hipoxia/etiología , Masculino , Persona de Mediana Edad , Oxígeno/sangre , Polisomnografía , Estudios Prospectivos , Trastornos Intrínsecos del Sueño/etiología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Heat stress is a significant environmental problem that has a detrimental impact on animal welfare and production efficiency in swine farms. The current study was conducted to assess the effect of low-intensity showers, provided during critical high-temperature hours daily, on body external temperature, feeding pattern, and carcass and meat quality characteristics in fattening pigs. A total of 400 animals (200 barrows and 200 gilts) were randomly allotted in 40 pens. A shower nozzle was installed over 20 pens (half barrows and half gilts) where pigs received a low-intensity shower for 2 min in 30 min intervals from 12 to 19 h (SHO group). Another group without showers was also considered (CON). Feeder occupancy measurement, thermographic measures, and carcass and meat quality parameters were studied. In the periods with higher environmental temperatures, SHO animals showed an increase in the feeder occupancy rate compared to the CON group. A decrease in temperature was observed after the shower, regardless of the anatomical location (p < 0.005). The treatment with showers led to higher values than in the CON group of 4.72%, 3.87%, 11.8%, and 15.1% for hot carcass weight, lean meat yield, and fat thickness in Longissimus Dorsi (LD) and Gluteus Medius muscles, respectively (p < 0.01). Pork from CON showed a 14.9% higher value of drip loss, and 18.9% higher malondialdehyde concentration than SHO (p < 0.01); meanwhile, intramuscular fat content was 22.8% higher in SHO than in CON (p < 0.01). On the other hand, the CON group exhibited higher L* (2.13%) and lower a* and b* values (15.8% and 8.97%) compared to the SHO group. However, the pH20h of the CON group was significantly lower than that of the SHO group (p < 0.001), indicating a softer pH decrease. Related to fatty acids in subcutaneous outer and inner layers and intramuscular fat, the CON group showed higher ΣSFA and lower ΣMUFA and Δ9-desaturase indexes than SHO (p < 0.05). In conclusion, the amelioration of heat stress through showers at critical times should be considered an interesting tool that improves both carcass and meat quality, as well as animal welfare.
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Forty-eight litters were used, with a total number of 645 piglets involved in the study. The split-suckling technique was applied to half of the litters at the end of farrowing by removing the heaviest piglets over three periods of 1 h. The piglets were individually weighed at 0, 1 d, and at weaning. Piglet losses were recorded daily. Traceability was maintained until the carcass splitting and meat analysis took place. Carcasses were eviscerated and weighed individually. Total mortality at weaning was affected by body weight, where the low-body-weight piglets showed a mortality rate almost four times higher than that of the normal-weight piglets. Mortality was highest in the first days of life, especially in the low-body-weight piglets. At weaning, split-suckling treatment caused a slight increase in mortality compared to the control group piglets (25% vs. 17.1%). Split-suckling had a positive effect on weight gain during the first 24 h of life (p = 0.014), and there was an interaction between treatment and parity (p = 0.007), with split-suckling being more effective in the primiparous sows compared to the multiparous sows. The piglets from litters receiving the split-suckling treatment had a lower average daily gain during the lactation period (p < 0.001) than the piglets from the control group. Weight gain during the first 24 h of life of the piglets subjected to split-suckling was higher than those of the control group. A lower IgG and α-tocopherol in plasma in the heavier piglets subjected to split-suckling treatment was observed in comparison to their respective control. The piglets from litters receiving the treatment showed a lower average daily gain during the lactation period (p < 0.001) than the piglets from the control group. No difference in slaughter weight was observed according to treatment. The pigs which received split-suckling treatment showed lower subcutaneous fat thickness (p < 0.0013) and higher lean meat yield (p < 0.0027), this effect being more marked in pigs from primiparous sows. Intramuscular fat concentration was higher in the Longissimus Dorsi muscle of the low-body-weight piglets. In the pigs that received split-suckling treatment, a higher concentration of C18:3n-3 (p = 0.036) and a tendency towards a higher concentration of C18:2n-6 (p = 0.107) and unsaturation index (p = 0.113) was observed in intramuscular fatty acids at slaughter, together with a lower concentration of C16:0 (p = 0.053) and SFA (p = 0.064). In conclusion, long-term response to split-suckling, particularly in low-birth-weight piglets, suggests an alteration in adiposity and metabolic regulation in these piglets that receive high levels of colostrum.
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BACKGROUND: Patients with polypharmacy suffer from complex medical conditions involving a large healthcare burden. This study aimed to describe the characteristics and utilization of primary care (PC) and hospital care (HC) and factors associated in chronic patients with polypharmacy, stratifying by adjusted morbidity groups (AMG) risk level, sex and age, and comparing with non-polypharmacy. METHODS: Cross-sectional study conducted in a Spanish basic healthcare area. Studied patients were those over 18 years with chronic diseases identified by the AMG tool from Madrid electronic clinical record, which was the data source. Sociodemographic, sociofunctional, clinical and healthcare utilization variables were described and compared by risk level, sex, age and having or not polypharmacy. Factors associated with healthcare utilization in polypharmacy patients were determined by a negative binomial regression model. RESULTS: In the area studied, 61.3% patients had chronic diseases, of which 16.9% had polypharmacy vs. 83.1% without polypharmacy. Patients with polypharmacy (vs. non-polypharmacy) mean age was 82.7 (vs. 52.7), 68.9% (vs. 60.7%) were women, and 22.0% (vs. 1.2%) high risk. Their average number of chronic diseases was 4.8 (vs. 2.2), and 95.6% (vs. 56.9%) had multimorbidity. Their mean number of annual healthcare contacts was 30.3 (vs. 10.5), 25.9 (vs. 8.8) with PC and 4.4 (vs. 1.7) with HC. Factors associated with a greater PC utilization in patients with polypharmacy were elevated complexity, high risk level and dysrhythmia. Variables associated with a higher HC utilization were also increased complexity and high risk, in addition to male sex, being in palliative care, having a primary caregiver, suffering from neoplasia (specifically lymphoma or leukaemia) and arthritis, whereas older age and immobilization were negatively associated. CONCLUSIONS: Polypharmacy population compared to non-polypharmacy was characterized by a more advanced age, predominance of women, high-risk, complexity, numerous comorbidities, dependency and remarkable healthcare utilization. These findings could help healthcare policy makers to optimize the distribution of resources and professionals within PC and HC systems, aiming for the improvement of polypharmacy management and rational use of medicines while reducing costs attributed to healthcare utilization by these patients.
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Swine industries worldwide face a loss in profit due to high piglet mortality, particularly as a consequence of the marked increase in prolificity and low birth weight (BW) of piglets. This research studied the effect of BW and individual neonatal care provided to piglets on preweaning mortality, and the long-term effects on growth and carcass and meat characteristics. Litters from seventy-one crossbred sows (PIC 34) were included in the trial. Half of each litter did not receive any further management, and the remaining half received the pre-established management protocol of early assistance of neonatal care (NC). Along lactation, the low-BW piglets (weight equal to or less than 1.1 kg) showed a threefold higher mortality rate than piglets of higher weights (32 vs. 10%; p = 0.001), with mortality particularly concentrated within the first week after birth. No effect of NC treatment was observed on mortality ratio caused by crushing, but a significant effect was observed in low-BW piglets who died of starvation (p < 0.01). The effect of NC on growth is dependent on BW, and heavier piglets at birth benefit from NC treatment to a higher extent than low-BW piglets. Low-BW piglets showed a higher fatness (p = 0.003), lower lean cut yield (p = 0.002) in carcasses, and higher intramuscular fat (IMF) content (2.29% vs. 1.91%; p = 0.01) in meat. NC treatment increased the lean content in carcasses from low-BW piglets (p < 0.01). The monounsaturated fatty acids concentration was higher in lower-than-normal-BW piglets (48.1% vs. 47.1%; p = 0.002) and the opposite effect was observed for polyunsaturated fatty acids (13.6% vs. 15.7%; p = 0.002). NC treatment induced a higher concentration of n-7 fatty acids. In conclusion, NC treatment may be a useful practice to reduce mortality in low-BW piglets. Moreover, NC could affect carcass fatness and meat quality, thus suggesting a long-term effect on metabolism.
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The new vaccines against SARS-CoV-2 have raised a lot of expectations about their ability to induce immunity and the duration of this. This is the case of mRNA vaccines such as Moderna's mRNA-1273. Therefore, it is necessary to study the humoral and cellular immunity generated by these vaccines. Our objectives are determining what is the normal response of antibody production, and what is the level of protective antibodies and monitoring patients in case of subsequent infection with COVID-19. We present the first results of a longitudinal study of the humoral response in 601 health workers vaccinated with Moderna. The results show a humoral immunity at 90 days after the second dose of 100%, with a strong decrease between the levels of circulating anti-S IgG antibodies between days 30 and 90 post-vaccination. Observing a steeper decline in those who had higher titles at the beginning. In addition, we present a cellular response of 86% at three months after the second dose, which is related to low humoral response.
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COVID-19 , Vacunas , Vacuna nCoV-2019 mRNA-1273 , Anticuerpos Antivirales , Vacuna BNT162 , COVID-19/prevención & control , Vacunas contra la COVID-19 , Humanos , Inmunidad Celular , Inmunidad Humoral , Estudios Longitudinales , SARS-CoV-2RESUMEN
BACKGROUND: Infection by the SARS-Cov-2 virus produces in humans a disease of highly variable and unpredictable severity. The presence of frequent genetic single nucleotide polymorphisms (SNPs) in the population might lead to a greater susceptibility to infection or an exaggerated inflammatory response. SARS-CoV-2 requires the presence of the ACE2 protein to enter in the cell and ACE2 is a regulator of the renin-angiotensin system. Accordingly, we studied the associations between 8 SNPs from AGTR1, ACE2 and ACE genes and the severity of the disease produced by the SARS-Cov-2 virus. METHODS: 318 (aged 59.6±17.3 years, males 62.6%) COVID-19 patients were grouped based on the severity of symptoms: Outpatients (n = 104, 32.7%), hospitalized on the wards (n = 73, 23.0%), Intensive Care Unit (ICU) (n = 84, 26.4%) and deceased (n = 57, 17.9%). Comorbidity data (diabetes, hypertension, obesity, lung disease and cancer) were collected for adjustment. Genotype distribution of 8 selected SNPs among the severity groups was analyzed. RESULTS: Four SNPs in ACE2 were associated with the severity of disease. While rs2074192 andrs1978124showed a protector effectassuming an overdominant model of inheritance (G/A vs. GG-AA, OR = 0.32, 95%CI = 0.12-0.82; p = 0.016 and A/G vs. AA-GG, OR = 0.37, 95%CI: 0.14-0.96; p = 0.038, respectively); the SNPs rs2106809 and rs2285666were associated with an increased risk of being hospitalized and a severity course of the disease with recessive models of inheritance (C/C vs. T/C-T/T, OR = 11.41, 95% CI: 1.12-115.91; p = 0.012) and (A/A vs. GG-G/A, OR = 12.61, 95% CI: 1.26-125.87; p = 0.0081). As expected, an older age (OR = 1.47), male gender (OR = 1.98) and comorbidities (OR = 2.52) increased the risk of being admitted to ICU or death vs more benign outpatient course. Multivariable analysis demonstrated the role of the certain genotypes (ACE2) with the severity of COVID-19 (OR: 0.31, OR 0.37 for rs2074192 and rs1978124, and OR = 2.67, OR = 2.70 for rs2106809 and rs2285666, respectively). Hardy-Weinberg equilibrium in hospitalized group for I/D SNP in ACE was not showed (p<0.05), which might be due to the association with the disease. No association between COVID-19 disease and the different AGTR1 SNPs was evidenced on multivariable, nevertheless the A/A genotype for rs5183 showed an higher hospitalization risk in patients with comorbidities. CONCLUSIONS: Different genetic variants in ACE2 were associated with a severe clinical course and death groups of patients with COVID-19. ACE2 common SNPs in the population might modulate severity of COVID-19 infection independently of other known markers like gender, age and comorbidities.
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Enzima Convertidora de Angiotensina 2/genética , COVID-19/patología , Peptidil-Dipeptidasa A/genética , Polimorfismo de Nucleótido Simple , Receptor de Angiotensina Tipo 1/genética , SARS-CoV-2/genética , Índice de Severidad de la Enfermedad , Anciano , COVID-19/genética , COVID-19/virología , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
AIMS: To describe the natural history of SARS-CoV-2 infection in patients with hypertrophic cardiomyopathy (HCM) compared with a control group and to identify predictors of adverse events. METHODS AND RESULTS: Three hundred and five patients [age 56.6 ± 16.9 years old, 191 (62.6%) male patients] with HCM and SARS-Cov-2 infection were enrolled. The control group consisted of 91 131 infected individuals. Endpoints were (i) SARS-CoV-2 related mortality and (ii) severe clinical course [death or intensive care unit (ICU) admission]. New onset of atrial fibrillation, ventricular arrhythmias, shock, stroke, and cardiac arrest were also recorded. Sixty-nine (22.9%) HCM patients were hospitalized for non-ICU level care, and 21 (7.0%) required ICU care. Seventeen (5.6%) died: eight (2.6%) of respiratory failure, four (1.3%) of heart failure, two (0.7%) suddenly, and three (1.0%) due to other SARS-CoV-2-related complications. Covariates associated with mortality in the multivariable were age {odds ratio (OR) per 10 year increase 2.25 [95% confidence interval (CI): 1.12-4.51], P = 0.0229}, baseline New York Heart Association class [OR per one-unit increase 4.01 (95%CI: 1.75-9.20), P = 0.0011], presence of left ventricular outflow tract obstruction [OR 5.59 (95%CI: 1.16-26.92), P = 0.0317], and left ventricular systolic impairment [OR 7.72 (95%CI: 1.20-49.79), P = 0.0316]. Controlling for age and sex and comparing HCM patients with a community-based SARS-CoV-2 cohort, the presence of HCM was associated with a borderline significant increased risk of mortality OR 1.70 (95%CI: 0.98-2.91, P = 0.0600). CONCLUSIONS: Over one-fourth of HCM patients infected with SARS-Cov-2 required hospitalization, including 6% in an ICU setting. Age and cardiac features related to HCM, including baseline functional class, left ventricular outflow tract obstruction, and systolic impairment, conveyed increased risk of mortality.
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Fibrilación Atrial , COVID-19 , Cardiomiopatía Hipertrófica , Disfunción Ventricular Izquierda , Humanos , Masculino , Adulto , Persona de Mediana Edad , Anciano , Femenino , COVID-19/complicaciones , COVID-19/epidemiología , SARS-CoV-2 , Cardiomiopatía Hipertrófica/complicaciones , Cardiomiopatía Hipertrófica/epidemiología , Sistema de Registros , Disfunción Ventricular Izquierda/complicaciones , Fibrilación Atrial/complicacionesRESUMEN
PURPOSE: To analyze the correlation of genomic instability with leukocyte infiltrate in gastrointestinal carcinomas (GIACs) and with tumor immunogenicity, e.g., HLA class I cell surface expression defects and galectin-3 and PDL-1 expression. EXPERIMENTAL DESIGN: Lymphocyte and macrophage infiltrations were immunohistochemically studied in HLA class I negative GIACs with sporadic high-level microsatellite instability (MSI-H) or microsatellite stability (MSS). RESULTS: Tumors with MSI-H were associated with the following: dense infiltration (CD45, P < 0.001); cytotoxic CD8-positive lymphocytes (P < 0.001); and a complete absence of HLA class I cell surface expression, due to inactivating ß2-microglobulin (ß2-m) mutation in 50% of cases. In contrast, HLA class I negative tumors with MSS were significantly associated with fewer CD8-positive lymphocytes. There was no association between microsatellite instability and other molecular features of the tumor cells, including expression of galectin-3. Finally, macrophage infiltrate in the tumors was not correlated with microsatellite instability or HLA class I cell surface expression (CD64, P = 0.63; CD163, P = 0.51). CONCLUSIONS: Microsatellite instability appears to be the most important factor determining the composition, density, and localization of leukocyte infiltrate, which is independent of other molecular features such expression of HLA class I cells, galectin-3, or programmed death ligand-1. Accordingly, the strong intratumoral CD8+ T infiltration of MSI-H tumors may be produced by elevated levels of specific inflammatory chemokines in the tumor microenvironment.
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Adenocarcinoma/genética , Adenocarcinoma/inmunología , Neoplasias Gastrointestinales/genética , Neoplasias Gastrointestinales/inmunología , Inestabilidad de Microsatélites , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD/genética , Antígenos CD/inmunología , Antígeno B7-H1 , Regulación hacia Abajo , Femenino , Galectina 3/genética , Galectina 3/inmunología , Neoplasias Gastrointestinales/patología , Antígenos de Histocompatibilidad Clase I/genética , Antígenos de Histocompatibilidad Clase I/inmunología , Humanos , Linfocitos Infiltrantes de Tumor/inmunología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Resultado del Tratamiento , Microglobulina beta-2/genética , Microglobulina beta-2/inmunologíaRESUMEN
Administering preoperative radiochemotherapy (RCT) in stage II-III tumors to locally advanced rectal carcinoma patients has proved to be effective in a high percentage of cases. Despite this, 20-30% of patients show no response or even disease progression. At present, preoperative response is assessed by a combination of imaging and tumor regression on histopathology, but recent studies suggest that various genetic abnormalities may be associated with the sensitivity or resistance of rectal cancer tumor cells to neoadjuvant therapy. In the present study we investigated the relationship between genetic lesions detected by high-density single-nucleotide polymorphisms (SNP) arrays 6.0 and response to neoadjuvant RCT, evaluated according to Dworak criteria in 39 rectal cancer tumors before treatment. The highest frequency of copy-number (CN) losses detected corresponded to chromosomes 18q (n = 27; 69%), 1p (n = 22; 56%), 15q (n = 19; 49%), 8p (n = 18; 48%), 4q (n = 17; 46%), and 22q (n = 17; 46%); in turn, CN gains more frequently involved chromosomes 20p (n = 22; 56%), 8p (n = 20; 51%), and 15q (n = 16; 41%). There was a significant association between alterations in the 1p, 3q, 7q, 12p, 17q, 20p, and 22q chromosomal regions and the degree of response to therapy prior to surgery. However, 4q, 15q11.1, and 15q14 chromosomal region alterations were identified as important by five prediction algorithms, i.e., those with the greatest influence on predicting the tumor response to treatment with preoperative RCT. Multivariate analysis of prognostic factors showed that gains on 15q11.1 and carcinoembryonic antigen (CEA) levels serum at diagnosis were the only independent variables predicting disease-free survival (DFS). Lymph node involvement also showed a prognostic impact on overall survival (OS) in the multivariate analysis. A deep-learning-based algorithm showed a 100% success rate in predicting both DFS and OS at 60 months after diagnosis of the disease. In summary, our results indicate the existence of an association between tumor genetic abnormalities at diagnosis, response to neoadjuvant therapy, and survival of patients with locally advanced rectal cancer. In addition to the clinical and biological characteristics of locally advanced rectal cancer patients, these could be used in the future as therapeutic and prognostic biomarkers, to identify patients sensitive or resistant to preoperative treatment, helping guide therapeutic decision-making. Additional prospective studies in larger series of patients are required to confirm the clinical utility of the newly identified biomarkers.
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INTRODUCTION: Pleural disease involves a large number of admissions and long hospital stays. In order to improve this situation, a Pleural Unit (PU) was created in our hospital. Our aim was to analyze the clinical impact of this unit. MATERIAL AND METHODS: In this prospective study, we included patients admitted to the PU of the Hospital Universitario Central de Asturias for primary spontaneous pneumothorax (PSP), secondary spontaneous pneumothorax (SSP), complicated parapneumonic pleural effusion (CPPE), and malignant pleural effusion (MPE) between January 2015 and December 2018. We analyzed descriptive parameters, mean length of stay, readmissions at 1 month, need for surgery, and in the CPPE group, in-hospital mortality. The data were compared with those of patients admitted to the respiratory medicine department for the same diseases during the previous two years (2013-2014). We also describe all procedures performed in the PU, in both inpatients and outpatients. RESULTS: A total of 741 patients were included, We observed a progressive decrease in total admissions for pleural diseases and mean length of stay (days) (with the exception of MPE), as follows: PSP: from 6.2 to 4.2 (P=.004); SSP: 13.2 to 8.6 (P=.005), MPE: 10.3 to 12.3 (P=.05); and CPPE: 18.3 to 11.3 (P=.001) There was a reduction in hospital readmissions at 1 month and in in-hospital mortality due to CPPE in the PU period (14.9% to 5.5%) (P=.021). CONCLUSIONS: The creation of a PU could decrease the number of unnecessary admissions, and reduce mean lengths of stay and, in the case of CPPE, in-hospital mortality.