Subject(s)
Dyspnea , alpha 1-Antitrypsin Deficiency , alpha 1-Antitrypsin , Humans , alpha 1-Antitrypsin/blood , alpha 1-Antitrypsin/genetics , alpha 1-Antitrypsin Deficiency/blood , alpha 1-Antitrypsin Deficiency/complications , alpha 1-Antitrypsin Deficiency/diagnosis , alpha 1-Antitrypsin Deficiency/genetics , Mutation , Female , Middle Aged , Dyspnea/blood , Dyspnea/diagnosis , Dyspnea/genetics , Lung/diagnostic imaging , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: The PI*S variant is one of the most prevalent mutations within alpha-1 antitrypsin deficiency (AATD). The risk of developing AATD-related lung disease in individuals with the PI*SS genotype is poorly defined despite its substantial prevalence. Our study aimed to characterize this genotype and its risk for lung disease and compare it with the PI*ZZ and PI*SZ genotypes using data from the European Alpha-1 antitrypsin Deficiency Research Collaboration international registry. METHOD: Demographic, clinical, functional, and quality of life (QoL) parameters were assessed to compare the PI*SS characteristics with the PI*SZ and PI*ZZ controls. A propensity score with 1:3 nearest-neighbour matching was performed for the most important confounding variables. RESULTS: The study included 1007 individuals, with PI*SS (n = 56; 5.6%), PI*ZZ (n = 578; 57.4%) and PI*SZ (n = 373; 37.0%). The PI*SS population consisted of 58.9% men, with a mean age of 59.2 years and a mean FEV1(% predicted) of 83.4%. Compared to PI*ZZ individuals they had less frequent lung disease (71.4% vs. 82.2%, p = 0.037), COPD (41.4% vs. 60%, p = 0.002), and emphysema (23.2% vs. 51.9%, p < 0.001) and better preserved lung function, fewer exacerbations, lower level of dyspnoea, and better QoL. In contrast, no significant differences were found in the prevalence of lung diseases between PI*SS and PI*SZ, or lung function parameters, exacerbations, dyspnoea, or QoL. CONCLUSIONS: We found that, as expected, the risk of lung disease associated with the PI*SS genotype is significantly lower compared with PI*ZZ, but does not differ from that observed in PI*SZ individuals, despite having higher serum AAT levels. TRIAL REGISTRATION: www. CLINICALTRIALS: gov (ID: NCT04180319).
Subject(s)
Genotype , alpha 1-Antitrypsin Deficiency , alpha 1-Antitrypsin , Humans , Male , Female , Middle Aged , alpha 1-Antitrypsin/genetics , alpha 1-Antitrypsin Deficiency/genetics , alpha 1-Antitrypsin Deficiency/epidemiology , alpha 1-Antitrypsin Deficiency/diagnosis , Aged , Lung Diseases/genetics , Lung Diseases/epidemiology , Lung Diseases/diagnosis , Risk Factors , Registries , Quality of LifeABSTRACT
OBJECTIVE: To evaluate the effect of selective decontamination of the digestive tract (SDD) on hospital-acquired infections (HAIs) in patients with acute burn injury requiring admission to a Burns Unit (BU). DESIGN: Retrospective before-and-after cohort study, between January 2017 and June 2023. SDD was implemented in March 2019, dividing patients into two groups. SETTING: Four-bed BU, in a referral University Hospital in Spain. PATIENTS: All the patients admitted during the study period were eligible for analysis. Patients who died or were discharged within 48hours of admission, and patients with an estimated survival less than 10% not considered for full escalation of therapy were excluded. INTERVENTION: SDD comprised the administration of a 4-day course of an intravenous antibiotic, and an oral suspension and oral topical paste of non-absorbable antibiotics during the stay in the BU. MAIN VARIABLE OF INTEREST: Incidence of HAIs during the stay in the BU. SECONDARY OUTCOMES: incidence of specific types of infections by site (bacteremia, pneumonia, skin and soft tissue infection) and microorganism (Gram-positive, Gram-negative, fungi), and safety endpoints. RESULTS: We analyzed 72 patients: 27 did not receive SDD, and 45 received SDD. The number of patients who developed HAIs were 21 (77.8%) and 21 (46.7%) in the non-SDD and the SDD groups, respectively (p=0.009). The number of hospital-acquired infectious episodes were 2.52 (1.21-3.82) and 1.13 (0.54-1.73), respectively (p=0.029). CONCLUSIONS: SDD was associated with a reduced incidence of bacterial HAIs and a decrease in the number of infectious episodes per patient.
ABSTRACT
BACKGROUND: Alpha-1 antitrypsin deficiency is an underdiagnosed genetic condition that predisposes to pulmonary complications and is mainly caused by rs28929474 (PI*Z allele) and rs17580 (PI*S allele) mutations in the SERPINA1 gene. OBJECTIVE: Development of a homogeneous genotyping test for detection of PI*S and PI*Z alleles based on the principles of allele-specific PCR and amplicon melting analysis with a fluorescent dye. METHODS: Sixty individuals, which included all possible genotypes that result from combinations of rs28929474 and rs17580 single nucleotide variants, were assayed with tailed allele-specific primers and SYBR Green dye in a real-time PCR machine. RESULTS: A clear discrimination of mutant and wild-type variants was achieved in the genetic loci that define PI*S and PI*Z alleles. Specific amplicons showed a difference of 2.0 °C in melting temperature for non-S and S variants and of 2.9 °C for non-Z and Z variants. CONCLUSIONS: The developed genotyping method is robust, fast, and easily scalable on a standard real-time PCR platform. While it overcomes the handicaps of non-homogeneous approaches, it greatly reduces genotyping costs compared with other homogeneous approaches.
Subject(s)
Alleles , Benzothiazoles , Diamines , Organic Chemicals , Quinolines , Real-Time Polymerase Chain Reaction , alpha 1-Antitrypsin , alpha 1-Antitrypsin/genetics , Humans , Real-Time Polymerase Chain Reaction/methods , alpha 1-Antitrypsin Deficiency/genetics , Polymorphism, Single Nucleotide , Genotyping Techniques/methods , Genotype , Fluorescent Dyes/chemistryABSTRACT
Different studies have shown that carrying an alpha-1 antitrypsin (AAT) deficiency allele is an independent risk factor for developing lung cancer (LC). However, to date, little is known regarding whether carrying a deficiency allele may be a prognostic factor in the evolution of LC. A prospective observational study was carried out which consecutively included patients diagnosed with LC in University Hospital "Nuestra Señora de Candelaria" between December 2017 and August 2020. A blood sample was taken from each of the patients in order to determine both AAT serum concentration and genotype. Based on AAT genotype, patients were divided into the deficiency (Pi*≠MM) or non-deficiency (Pi*=MM) group. One hundred and sixty-four patients were included. The average length of follow-up was 13±10 months. Patients were classified as stage I (4.2%), stage II (8.3%), stage III (31.2%) and stage IV (56.3%), according to tumour, node and metastasis (TNM) staging. Twenty-eight patients (17%) were carriers of a deficiency allele (6 Pi*MS, 1 Pi*MZ, 1 Pi*MMheerlen). No significant differences were found with respect to baseline characteristics between Pi*≠MM and Pi*=MM. Patients in the Pi*≠MM group had a higher risk of death in the first 6 months after the LC diagnosis compared to Pi*=MM subjects (HR =2.04; 95% CI: 1.04-4.0; P=0.038). The presence of an AAT deficiency genotype could be a potential prognostic marker in LC. However, larger studies that justify these findings are needed.
ABSTRACT
BACKGROUND: Diffuse large B-cell lymphoma comprises nearly 30% of non-Hodgkin lymphoma cases and patients with relapsed or refractory diffuse large B-cell lymphoma who are ineligible for stem-cell transplantation have few treatment options and poor prognoses. We aimed to determine whether the novel combination of polatuzumab vedotin in combination with rituximab and lenalidomide (Pola+R+Len) would provide a tolerable treatment option with enhanced antitumour response in patients with relapsed or refractory diffuse large B-cell lymphoma. METHODS: This completed phase 1b/2, open-label, multicentre, single-arm study (GO29834) evaluated the safety and efficacy of Pola+R+Len in patients with relapsed or refractory diffuse large B-cell lymphoma at 19 sites in three countries (USA, Spain, and UK). Patients (≥18 years old) were eligible for inclusion if they had histologically documented CD20-positive relapsed or refractory diffuse large B-cell lymphoma and Eastern Cooperative Oncology Group performance status of 2 or lower, had received at least one previous line of chemoimmunotherapy, including an anti-CD20 agent, and were ineligible for stem-cell transplantation. The dose-escalation phase (1b) used escalating doses of lenalidomide to find the recommended phase 2 dose. Patients received six 28-day cycles of induction treatment with intravenous rituximab 375 mg/m2 and intravenous polatuzumab vedotin 1·8 mg/kg (all cohorts) plus oral lenalidomide at the following doses: 10 mg (cohort A); 15 mg (cohort B); and 20 mg (cohort C). Rituximab and polatuzumab vedotin were administered on day 1 and lenalidomide on days 1-21 of each 28-day cycle. During the dose-expansion phase (2), patients received six 28-day cycles of Pola+R+Len at the recommended phase 2 dose established during dose escalation. In both phases, patients with a complete response or partial response at the end of induction were eligible for post-induction therapy with rituximab 375 mg/m2 on day 1 and lenalidomide 10 mg/day on days 1-21 of each 28-day cycle for a maximum of 6 cycles. The primary safety objective of the dose-escalation phase was identification of the maximum tolerated dose through incidence of dose-limiting toxic effects. The primary efficacy outcome of the dose-expansion phase was Independent Review Committee-assessed complete response rate at end of induction, based on PET-CT. Analyses were conducted in the safety population, which included all patients who received at least one dose of any study drug, and the efficacy population, which included all patients who received at least one dose of any study drug at the recommended phase 2 dose. This study is registered with ClinicalTrials.gov, number NCT02600897. FINDINGS: Between July 11, 2017 and Feb 3, 2020, 57 patients were enrolled (median age 71 years [IQR 60-75]; 38 [67%] were male and 19 (33%) were female; 47 [82%] were not Hispanic or Latino; and the median previous lines of therapy was 2 [IQR 1-3]). 18 participants were included in phase 1b and 39 were included in phase 2. Phase 1b confirmed a 20 mg recommended phase 2 dose for lenalidomide. After a median follow-up of 11·8 months (IQR 4·7-25·8), the complete response rate, as assessed by the Independent Review Committee, was 31% (90% CI 20-43). The most common grade 3-4 adverse events were neutropenia (35 [61%] of 57) and thrombocytopenia (eight [14%] of 57). Serious adverse events were reported in 23 (40%) of 57 patients and one patient died due to a treatment-related adverse event (neutropenic sepsis). INTERPRETATION: Although the combination of Pola+R+Len did not meet the prespecified activity threshold, some patients derived clinical benefit and the regimen had a tolerable safety profile in patients with relapsed or refractory diffuse large B-cell lymphoma. FUNDING: Genentech/F Hoffmann-La Roche.
Subject(s)
Antibodies, Monoclonal , Immunoconjugates , Lymphoma, Large B-Cell, Diffuse , Lymphoma, Non-Hodgkin , Neutropenia , Humans , Male , Female , Aged , Adolescent , Rituximab/adverse effects , Lenalidomide/therapeutic use , Positron Emission Tomography Computed Tomography , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Lymphoma, Non-Hodgkin/drug therapy , Lymphoma, Large B-Cell, Diffuse/pathology , Neutropenia/etiologyABSTRACT
The 1,8-Diazaanthracene-2,9,10-triones, their 5,8-dihydro derivatives, and 1,8-diazaanthracene-2,7,9,10-tetraones, structurally related to the diazaquinomycin family of natural products, were synthesized in a regioselective fashion employing Diels-Alder strategies. These libraries were studied for their cytotoxicity in a variety of human cancer cell lines in order to establish structure-activity relationships. From the results obtained, we conclude that some representatives of the 1,8-diazaanthracene-2,9,10-trione framework show potent and selective cytotoxicity against solid tumors. Similar findings were made for the related 1-azaanthracene-2,9,10-trione derivatives, structurally similar to the marcanine natural products, which showed improved activity over their natural counterparts. An enantioselective protocol based on the use of a SAMP-related chiral auxiliary derived was developed for the case of chiral 5-substituted 1,8-diazaanthracene-2,9,10-triones, and showed that their cytotoxicity was not enantiospecific.
Subject(s)
Anthracenes , Biological Products , Humans , Cell Line , Structure-Activity RelationshipABSTRACT
Introducción y objetivo: El cáncer de mama es la neoplasia maligna con mayor incidencia y prevalencia mundial (excluyendo tumores cutáneos no melanoma), con cifras crecientes. Por ello, cualquier tejido extraído de la mama, con independencia del motivo, debe ser enviado a estudio anatomopatológico. El objetivo de este estudio es determinar la prevalencia de lesiones premalignas y carcinoma oculto en las piezas de resección de mamas intervenidas por motivos no oncológicos durante 5 años en el Servicio de Cirugía Plástica, Estética y Reparadora del Hospital Universitario Río Hortega de Valladolid, España. Material y método: Analizamos las piezas de resección mamaria de 253 pacientes sin diagnóstico clínico de cáncer de mama clasificadas previamente en grupos de riesgo teórico creciente de neoplasia asociada, con el objetivo de identificar la prevalencia de lesiones premalignas y carcinoma oculto en nuestra población. Resultados: La prevalencia de lesiones malignas mostró un incremento progresivo desde el grupo control (2.25%): pacientes sin antecedente personal de neoplasia mamaria ni factor de riesgo genético, a los grupos A (7.07%): pacientes con antecedente de neoplasia mamaria; B (11.43%): pacientes con factor de riesgo genético; y C (16.67%): pacientes con antecedente de neoplasia mamaria y factor de riesgo genético, con una edad media al diagnóstico de 48.11 años. Conclusiones: Los resultados obtenidos se correlacionan con la literatura existente y ponen de manifiesto que el hallazgo casual de lesiones premalignas y malignas en pacientes sin diagnóstico de cáncer de mama es una realidad relativamente común, especialmente en mujeres con factores de riesgo genético y/o diagnóstico de neoplasia mamaria previa.Nivel de evidencia científica 4b Diagnóstico
Background and objective: Breast cancer is the malignancy with the highest incidence and prevalence worldwide (excluding non-melanoma skin cancer), with growing rates. This is why any tissue removed from a breast (whatever the cause) must be properly analyzed. The aim of this study is to determine the prevalence of premalignant lesions and occult carcinoma in resected breast specimens operated for non-oncological reasons over a period of 5 years in the Plastic, Aesthetic, and Reconstructive Surgery Department at the Río Hortega University Hospital in Valladolid, Spain. Methods: We analyzed the breast resection specimens belonging to 253 patients without a clinical diagnosis of breast cancer, previously classified in groups of increasing theoretical risk of breast cancer, with the aim of identifying the prevalence of premalignant lesions and occult carcinoma in our population. Results: The prevalence of malignant lesions showed a progressive increase from the control group (2.25%): patients without personal history of breast neoplasia or genetic risk factor; to groups A (7,07%): patients with history of breast neoplasia; B (11.43%): patients with genetic risk factor; and C (16.67%): patients with history of breast neoplasia and genetic risk factor, with an average age at diagnosis of 48.11 years. Conclusions: The results correlate with the existing literature show that the casual finding of premalignant and malignant lesions in patients without a diagnosis of breast cancer is relatively common, especially in women with genetic risk factors and/or a prior diagnosis of breast cancer.(AU)
Subject(s)
Humans , Female , Carcinoma , Breast Neoplasms/surgery , Mammaplasty , Mastectomy , Breast Implants , Prevalence , Retrospective Studies , Surgery, Plastic , Breast NeoplasmsSubject(s)
Humans , Male , Middle Aged , Poisoning , Cobalt/toxicity , Hip Prosthesis/adverse effectsSubject(s)
Humans , Male , Female , Referral and Consultation , Pulmonary Medicine , Smokers , Ex-Smokers , Tobacco Use Disorder/complications , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/diagnosis , Respiratory Tract Diseases , Spain , Primary Health Care , Prospective StudiesABSTRACT
No disponible
Subject(s)
Humans , Coronavirus Infections/diagnosis , Diagnostic Techniques and Procedures , RNA/genetics , Enzyme-Linked Immunosorbent Assay , Immunoglobulin M , Immunoglobulin A , Pneumonia, Viral/diagnosis , Sensitivity and SpecificityABSTRACT
No disponible
Subject(s)
Humans , Female , Middle Aged , Granuloma, Respiratory Tract/drug therapy , Lamotrigine/administration & dosage , Epilepsy, Absence/drug therapy , Exanthema/drug therapy , Blood Gas Analysis/methods , Tomography, Emission-Computed , Sputum/cytology , Immunohistochemistry , Diagnosis, Differential , Drug Hypersensitivity/complicationsABSTRACT
OBJETIVO: Analizar la prevalencia y el manejo de los episodios de dolor, su evaluación y registro en unidades de hospitalización de Medicina Interna en un hospital público de tercer nivel del Servicio Regional de Salud de Castilla y León. MÉTODO: Estudio descriptivo transversal sobre los pacientes ingresados en unidades de Medicina Interna. La prevalencia del dolor se detectó mediante el cuestionario Brief Pain Inventory. La gestión de los episodios se analizó mediante su registro en la historia clínica. RESULTADOS: Se incluyeron 83 pacientes, el 73,5% manifestaron dolor y el 67,2% desconocían su pauta analgésica. Se identificaron más episodios de dolor en el caso de las mujeres (p = 0,006) con respecto a los hombres. La administración farmacológica se registró en todos los casos, el episodio de dolor dentro del evolutivo de la enfermera se registró en el 29,5% y en ningún caso se registró intensidad o grado de alivio con la Escala Visual Analógica, en la gráfica de constantes. CONCLUSIONES: Se ha evidenciado una alta prevalencia de dolor en los pacientes hospitalizados y una deficiencia en la gestión de los episodios de dolor por parte de las enfermeras, tanto en la evaluación como en el registro. Ello implica la necesidad de protocolizar el control del dolor implementando buenas prácticas basadas en la evidencia y dotar a las enfermeras de los medios y el apoyo necesario para poder realizar un manejo adecuado del dolor
OBJECTIVE: To analyze the prevalence and management of pain episodes, their evaluation and recording in internal medicine hospitalization units in a third level public hospital of the regional health service of Castilla y León. METHOD: A descriptive cross-sectional study. The study population comprised patients hospitalized in internal medicine units. Pain prevalence was detected by the Brief Pain Inventory questionnaire. The management of pain episodes was analyzed as recorded in the clinical records. RESULTS: 83 patients were included, 73.5% of them reported pain and 67.2% did not know their analgesia regimen. More episodes of pain were identified in the women (P=.006) than in the men. The pharmacological administration was recorded in all cases; however, nurses recorded the episode in the clinical history of 29.5% of the patients. In no case, was the pain intensity or degree of relief recorded using the visual analogical scale. CONCLUSIONS: There is evidence of a high prevalence of pain in hospitalized patients and deficiencies in the management of pain episodes by nurses, both in evaluation and recording. This implies the need for pain control protocols and the implementation of evidence-based best practice guidelines to provide nurses with the means and support for adequate pain management
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Aged, 80 and over , Pain/epidemiology , Hospital Units , Pain/nursing , Internal MedicineABSTRACT
No disponible
Subject(s)
Humans , Male , Female , Young Adult , Adult , Middle Aged , Tobacco Use Disorder/epidemiology , Tobacco Use/epidemiology , Tobacco Smoking/epidemiology , Surveys and Questionnaires/statistics & numerical data , Health Personnel/statistics & numerical data , Inpatient Care Units , Age of OnsetABSTRACT
No disponible