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1.
medRxiv ; 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38946991

RESUMEN

Sepsis is the leading cause of death of hospitalized children worldwide. Despite the established link between immune dysregulation and mortality in pediatric sepsis, it remains unclear which host immune factors contribute causally to adverse sepsis outcomes. Identifying modifiable pathobiology is an essential first step to successful translation of biologic insights into precision therapeutics. We designed a prospective, longitudinal cohort study of 88 critically ill pediatric patients with multiple organ dysfunction syndrome (MODS), including patients with and without sepsis, to define subphenotypes associated with targetable mechanisms of immune dysregulation. We first assessed plasma proteomic profiles and identified shared features of immune dysregulation in MODS patients with and without sepsis. We then employed consensus clustering to define three subphenotypes based on protein expression at disease onset and identified a strong association between subphenotype and clinical outcome. We next identified differences in immune cell frequency and activation state by MODS subphenotype and determined the association between hyperinflammatory pathway activation and cellular immunophenotype. Using single cell transcriptomics, we demonstrated STAT3 hyperactivation in lymphocytes from the sickest MODS subgroup and then identified an association between STAT3 hyperactivation and T cell immunometabolic dysregulation. Finally, we compared proteomics findings between patients with MODS and patients with inborn errors of immunity that amplify cytokine signaling pathways to further assess the impact of STAT3 hyperactivation in the most severe patients with MODS. Overall, these results identify a potentially pathologic and targetable role for STAT3 hyperactivation in a subset of pediatric patients with MODS who have high severity of illness and poor prognosis.

2.
Respir Res ; 25(1): 260, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38926693

RESUMEN

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).


Asunto(s)
Genotipo , Deficiencia de alfa 1-Antitripsina , alfa 1-Antitripsina , Humanos , Masculino , Femenino , Persona de Mediana Edad , alfa 1-Antitripsina/genética , Deficiencia de alfa 1-Antitripsina/genética , Deficiencia de alfa 1-Antitripsina/epidemiología , Deficiencia de alfa 1-Antitripsina/diagnóstico , Anciano , Enfermedades Pulmonares/genética , Enfermedades Pulmonares/epidemiología , Enfermedades Pulmonares/diagnóstico , Factores de Riesgo , Sistema de Registros , Calidad de Vida
3.
J Reconstr Microsurg ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38848754

RESUMEN

BACKGROUND: Lymphedema is a chronic condition, characterized by fluid buildup and tissue swelling and is caused by impairment of the lymphatic system. The lymph interpositional flap transfer technique, in which lymph flow is restored with a flap that includes subdermal lymphatic channels, is an option for surgical reconstruction. The superficial circumflex iliac artery perforator (SCIP) flap can be used for this purpose. This study aimed to describe and characterize the lymphatic patterns within the vascular territory of the SCIP flap. METHODS: This cross-sectional multicenter study involved 19 healthy volunteers aged ≥18 years of both sexes assessing the bilateral SCIP flap zone. Superficial lymphatic patterns were evaluated at 4-, 14-, and 24 minutes after indocyanine green (ICG) lymphography injection. Standardized procedures were implemented for all participants in both hospitals. RESULTS: The linear pattern was predominant bilaterally. The median number of lymphatic vessels and their length increased over time. Most lymphatic vessels in the SCIP flap were oriented toward the inguinal lymph node (ILN). However, the left SCIP zone lymphatic vessels were directed opposite to the ILN. CONCLUSION: The two sides SCIP zones were not significantly different. The primary direction of the bilateral lymphatic vessels was toward the ILN, although only single-side lymphatic vessels were in the opposite direction. These findings emphasize the importance of assessing lymphatic axiality and coherent lymphatic patterns prior to undertaking the SCIP as an interposition flap, to ensure effective restoration of lymphatic flow.

4.
J Thorac Dis ; 16(5): 3484-3492, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38883634

RESUMEN

Sarcomas of the chest wall are rare and their current treatment regimen is diverse and complex due to the heterogeneity of these tumors as well as the variations in tumor location and extent. They only account for 0.04% of newly diagnosed cancers of whom about 45% comprise soft tissue sarcomas. Larger cohort studies are scarce and often focus on one specific treatment item. We therefore aim to provide helicopter view for clinicians treating patients with sarcomas of the chest wall, focusing mainly on soft tissue sarcomas. This overview includes the value of neoadjuvant systemic or radiotherapy, surgical resection, approaches for thoracic wall reconstruction, and the need for follow-up. Provided the heterogeneity and relative rarity, we recommend that treatment decisions in soft tissue sarcoma of the chest wall are discussed in a multidisciplinary tumor board at a reference sarcoma center or within sarcoma networks to ensure personalized, rational decision making. A surgical oncologist specialized in sarcoma surgery is crucial, and for extensive resections involving the thoracic cavity we recommend involvement of a thoracic surgeon. In addition, a specialized medical- and radiation oncologist as well as a plastic surgeon is required to ensure the best multimodality treatment plan to optimize patient outcome.

5.
Clin Transl Oncol ; 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38896340

RESUMEN

BACKGROUND: This study examines lung cancer incidence in Spain (1990-2019) through age-period-cohort (A-P-C) analysis and Global Burden of Diseases (GBD) data, unravelling the complex interplay of age, period, and birth cohort in shaping these trends. METHODS: Utilizing GBD and Spanish population data, the study calculates age-standardized incidence rates (ASIRs) and employs Joinpoint analysis to identify significant trends. A-P-C analysis dissects the individual effects of age, calendar period, and birth cohort on incidence patterns. RESULTS: Between 1990 and 2019, almost 738,000 cases of lung cancer were diagnosed in Spain, with an average annual increase of 1.7%. The ASIR of lung cancer in Spain from 1990 to 2019 showed a sustained upward trend in women (Average Annual Per cent Change: 2.5%, P < 0.05), reaching 23.3 cases per 100,000 in 2019, whilst men experienced a significant decrease in incidence rates (AAPC: -0.6%, P < 0.05), falling to 108.9 in 2019. The male-to-female incidence ratio decreased from 12.2 in 1992 to 4.9 in 2019. Joinpoint analysis identified distinct periods for both sexes, with men showing stability, decline and then a significant decrease, whereas women showed an initial increase followed by a decrease. The longitudinal age curves showed a consistently higher incidence risk in men, peaking in the 80-84 age group. Male cohorts since the 1920s showed a decreasing relative risk, whereas women showed fluctuations in risk over time. CONCLUSION: Lung cancer rates are falling in Spain, especially amongst men, due to lower smoking rates. The gender gap is closing, but prevention targeted at women is needed. Tighter tobacco control and research into other risk factors are essential. Understanding the long-term effects of smoking and early exposure is key to better prevention and treatment in Spain.

6.
J Plast Reconstr Aesthet Surg ; 93: 290-298, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38754281

RESUMEN

BACKGROUND: Lymphaticovenous anastomosis is widely used in lymphedema management. Although its effectiveness in reducing edema in patients can be clinically observed, evaluating the long-term outcomes of this technique can be complex. This study established an animal model to assess the outcomes of lymphaticovenous anastomosis technique at 15 and 30-days post-surgery using indocyanine green lymphography, Patent Blue V dye injection, and histopathological examination. METHODS: An experimental model was established in the hindlimbs of 10 rabbits using the popliteal vein and afferent lymphatic vessels in the popliteal area. The subjects were divided into two groups: the first group (n = 5) underwent patency assessment at 0 and 15 days, and the second group (n = 5) at 0 and 30-days, resulting in 20 anastomoses. Patency was verified at 0, 15, and 30-days using indocyanine green lymphography and Patent Blue V injection. Histopathological examinations were performed on the collected anastomosis samples. RESULTS: The patency rate was 90% (19/20) initially, 60% (6/10) at 15 days post-surgery, and 80% (8/10) at 30-days. The average diameter of lymphatic vessels and veins was 1.0 mm and 0.8 mm, respectively. The median number of collateral veins was 3; the median surgical time was 65.8 min. Histopathology revealed minimal endothelial damage and inflammatory responses due to the surgical sutures, with vascular inflammation and thrombosis in a single case. Local vascular neoformations were observed. CONCLUSION: This study highlights the reliability and reproducibility of using rabbits as experimental models for training in lymphaticovenous anastomosis technique owing to the accessibility of the surgical site and dimensions of their popliteal vasculature.


Asunto(s)
Anastomosis Quirúrgica , Verde de Indocianina , Vasos Linfáticos , Linfedema , Linfografía , Microcirugia , Animales , Conejos , Anastomosis Quirúrgica/métodos , Vasos Linfáticos/cirugía , Vasos Linfáticos/diagnóstico por imagen , Microcirugia/métodos , Linfografía/métodos , Linfedema/cirugía , Grado de Desobstrucción Vascular , Modelos Animales , Modelos Animales de Enfermedad , Vena Poplítea/cirugía , Miembro Posterior/irrigación sanguínea , Miembro Posterior/cirugía , Colorantes , Colorantes de Rosanilina
7.
Arch Bronconeumol ; 60(7): 417-422, 2024 Jul.
Artículo en Inglés, Español | MEDLINE | ID: mdl-38729884

RESUMEN

INTRODUCTION: Treatment with LABA/LAMA is recommended in GOLD B patients. We hypothesized that triple therapy (LABA/LAMA/ICS) will be superior to LABA/LAMA in achieving and maintaining clinical control (CC), a composite outcome that considers both impact and disease stability in a subgroup of GOLD B patients (here termed GOLD B+ patients) characterized by: (1) remaining symptomatic (CAT≥10) despite regular LABA/LAMA therapy; (2) having suffered one moderate exacerbation in the previous year; and (3) having blood eosinophil counts (BEC) ≥150cells/µL. METHODS: The ANTES B+ study is a prospective, multicenter, open label, randomized, pragmatic, controlled trial designed to test this hypothesis. It will randomize 1028 B+ patients to continue with their usual LABA/LAMA combination prescribed by their attending physician or to begin fluticasone furoate (FF) 92µg/umeclidinium (UMEC) 55µg/vilanterol (VI) 22µg in a single inhaler q.d. for 12 months. The primary efficacy outcome will be the level of CC achieved. Secondary outcomes include the clinical important deterioration index (CID), annual rate of exacerbations, and FEV1. Exploratory objectives include the interaction of BEC and smoking status, all-cause mortality and proportion of patients on LABA/LAMA arm that switch therapy arms. Safety analysis include adverse events and incidence of pneumonia. RESULTS: The first patient was recruited on February 29, 2024; results are expected in the first quarter of 2026. CONCLUSIONS: The ANTES B+ study is the first to: (1) explore the efficacy and safety of triple therapy in a population of B+ COPD patients and (2) use a composite index (CC) as the primary result of a COPD trial.


Asunto(s)
Alcoholes Bencílicos , Combinación de Medicamentos , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Estudios Prospectivos , Alcoholes Bencílicos/uso terapéutico , Alcoholes Bencílicos/administración & dosificación , Clorobencenos/uso terapéutico , Clorobencenos/administración & dosificación , Quinuclidinas/uso terapéutico , Quinuclidinas/administración & dosificación , Quimioterapia Combinada , Antagonistas Muscarínicos/uso terapéutico , Antagonistas Muscarínicos/administración & dosificación , Androstadienos/uso terapéutico , Androstadienos/administración & dosificación , Resultado del Tratamiento , Corticoesteroides/uso terapéutico , Broncodilatadores/uso terapéutico , Broncodilatadores/administración & dosificación , Administración por Inhalación , Masculino , Femenino , Agonistas de Receptores Adrenérgicos beta 2/uso terapéutico , Agonistas de Receptores Adrenérgicos beta 2/administración & dosificación , Eosinófilos , Persona de Mediana Edad
8.
Mol Biol Rep ; 51(1): 582, 2024 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-38678168

RESUMEN

BACKGROUND: Hybridization associated with polyploidy studies is rare in the tropics. The genus Zygopetalum (Orchidaceae) was investigated here as a case study of Neotropical plants. In the rocky highlands of the Ibitipoca State Park (ISP), southeast Brazil, individuals with intermediate colors and forms between the species Z. maculatum and Z. triste were commonly identified. METHODS AND RESULTS: Chromosomal analysis and DNA quantity showed a uniform population. Regardless of the aspects related to the color and shape of floral structures, all individuals showed 2n = 96 chromosomes and an average of 14.05 pg of DNA. Irregularities in meiosis associated with chromosome number and C value suggest the occurrence of polyploidy. The genetic distance estimated using ISSR molecular markers revealed the existence of genetic variability not related to morphological clusters. Morphometric measurements of the flower pieces revealed that Z. maculatum shows higher variation than Z. triste although lacking a defined circumscription. CONCLUSION: The observed variation can be explained by the polyploid and phenotypic plasticity resulting from the interaction of the genotypes with the heterogeneous environments observed in this habitat.


Asunto(s)
Variación Genética , Orchidaceae , Fenotipo , Poliploidía , Orchidaceae/genética , Variación Genética/genética , Brasil , Cromosomas de las Plantas/genética , Genotipo , Flores/genética , Flores/anatomía & histología , Repeticiones de Microsatélite/genética , Hibridación Genética/genética
10.
Artículo en Inglés | MEDLINE | ID: mdl-38492558

RESUMEN

OBJECTIVES: Bar dislocation is one of the most feared complications of the minimally invasive repair of pectus excavatum. METHODS: Prospective randomized parallel-group clinical trial intending to assess whether oblique stabilizers can reduce bar displacement in comparison with regular stabilizers used in minimally invasive repair of pectus excavatum. Additionally, we evaluated pain, quality of life and other postoperative complications. Participants were randomly assigned to surgery with perpendicular (n = 16) or oblique stabilizers (n = 14) between October 2017 and September 2018 and followed for 3 years. Bar displacements were evaluated with the bar displacement index. Pain scores were evaluated through visual analogue scale and quality of life through the Pectus Excavatum Evaluation Questionnaire. RESULTS: Control group average displacement index was 17.7 (±26.7) and intervention group average displacement index was 8.2 (±10.9). There was 1 reoperation in each group that required correction with 2 bars. Bar displacement was similar among groups (P = 0.12). No other complications were recorded. There was no statistically significant difference on pain score. There was a significant difference between pre- and postoperative composite scores of the participants' body image domain and psycho-social aspects in both groups. The difference between the pre- and postoperative participants' perception of physical difficulties was greater and statistically significant in the intervention group. CONCLUSIONS: There was no statistical difference in the use of perpendicular or oblique stabilizers, but the availability of different models of stabilizers during the study suggested that this can be advantageous. The trial is registered at ClinicalTrials.gov, number NCT03087734.

11.
J Thorac Dis ; 16(2): 1724-1729, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38505023

RESUMEN

Sternal cleft (SC) is a rare congenital affection caused by the absence of sternal bar union. Diagnosis is generally made after birth due to paradoxical midline movement, although it can be made prenatally by ultrasonography. A computerized tomography scan (CT scan) after birth is generally used to confirm the diagnosis, assess other intrathoracic conditions, classify the SC, and plan for surgery. SC can be classified as complete or incomplete. A complete SC has a full gap between sternal bars. An incomplete SC is subdivided into superior or inferior, related to the point of bone fusion between the sternal bars. The goal of surgical treatment is to protect mediastinal structures. Many authors advocate the repair in newborn patients, although it can be performed in older patients. The main argument in its favor is the chest's flexibility, with a reduced risk of compression of the mediastinal structures. There are several cases of series and distinct surgical techniques in the literature. Some authors have suggested the use of autologous tissue, prosthetic material such as mesh, or titanium plates and screws. Although difficulties are often encountered in surgical access, they have not been discussed. Therefore, we are promoting modifications to the technique in response to this. The purpose is to show innovations, and how to deal with adversity during the procedure.

12.
J Thorac Dis ; 16(2): 1738-1740, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38505047
13.
ERJ Open Res ; 10(2)2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38529348

RESUMEN

Background: Some patients with COPD suffer frequent exacerbations (FE). We hypothesised that their systemic proteomic profile would be different from that of non-frequent exacerbators (NFE). The objective of the present study was to contrast the systemic proteomic profile in FE versus NFE. As a reference, we also determined the systemic proteomic profile of healthy controls (HC) and COPD patients during an actual episode of exacerbation (AE). Methods: In the analysis we included 40 clinically stable COPD patients (20 FE and 20 NFE), and 20 HC and 10 AE patients. Their plasma samples were analysed by combining two complementary proteomic approaches: label-free liquid chromatography-tandem mass spectrometry and multiplex immunoassays. Gene Ontology annotation, pathway enrichment and network analyses were used to investigate molecular pathways associated with differentially abundant proteins/peptides (DAPs). Results: Compared with HC, we identified 40 DAPs in FE, 10 in NFE and 63 in AE. Also compared to HC, pathway functional and protein-protein network analyses revealed dysregulation of inflammatory responses involving innate and antibody-mediated immunity in COPD, particularly in the FE group, as well as during an AE episode. Besides, we only identified alterations in the complement and coagulation cascades in AE. Conclusion: There are specific plasma proteome profiles associated with FE, which are partially shared with findings observed during AE, albeit others are uniquely present during the actual episode of AE.

14.
Science ; 383(6686): eadh4059, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38422122

RESUMEN

We describe humans with rare biallelic loss-of-function PTCRA variants impairing pre-α T cell receptor (pre-TCRα) expression. Low circulating naive αß T cell counts at birth persisted over time, with normal memory αß and high γδ T cell counts. Their TCRα repertoire was biased, which suggests that noncanonical thymic differentiation pathways can rescue αß T cell development. Only a minority of these individuals were sick, with infection, lymphoproliferation, and/or autoimmunity. We also report that 1 in 4000 individuals from the Middle East and South Asia are homozygous for a common hypomorphic PTCRA variant. They had normal circulating naive αß T cell counts but high γδ T cell counts. Although residual pre-TCRα expression drove the differentiation of more αß T cells, autoimmune conditions were more frequent in these patients compared with the general population.


Asunto(s)
Autoinmunidad , Linfocitos Intraepiteliales , Glicoproteínas de Membrana , Receptores de Antígenos de Linfocitos T alfa-beta , Humanos , Autoinmunidad/genética , Diferenciación Celular , Homocigoto , Linfocitos Intraepiteliales/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Glicoproteínas de Membrana/genética , Mutación con Pérdida de Función , Recuento de Linfocitos , Alelos , Infecciones/inmunología , Trastornos Linfoproliferativos/inmunología , Linaje , Masculino , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años
15.
Am J Clin Pathol ; 161(5): 501-511, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38340336

RESUMEN

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.


Asunto(s)
Productos de Degradación de Fibrina-Fibrinógeno , Selectina-P , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/sangre , Estudios de Casos y Controles , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Selectina-P/sangre , Biomarcadores de Tumor/sangre , Adulto , Neoplasias/complicaciones , Neoplasias Primarias Desconocidas/complicaciones , Neoplasias Primarias Desconocidas/diagnóstico
16.
Nat Commun ; 15(1): 1728, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38409095

RESUMEN

A better understanding of the relative roles of internal climate variability and external contributions, from both natural (solar, volcanic) and anthropogenic greenhouse gas forcing, is important to better project future hydrologic changes. Changes in the evaporative demand play a central role in this context, particularly in tropical areas characterized by high precipitation seasonality, such as the tropical savannah and semi-desertic biomes. Here we present a set of geochemical proxies in speleothems from a well-ventilated cave located in central-eastern Brazil which shows that the evaporative demand is no longer being met by precipitation, leading to a hydrological deficit. A marked change in the hydrologic balance in central-eastern Brazil, caused by a severe warming trend, can be identified, starting in the 1970s. Our findings show that the current aridity has no analog over the last 720 years. A detection and attribution study indicates that this trend is mostly driven by anthropogenic forcing and cannot be explained by natural factors alone. These results reinforce the premise of a severe long-term drought in the subtropics of eastern South America that will likely be further exacerbated in the future given its apparent connection to increased greenhouse gas emissions.

17.
J Clin Med ; 13(4)2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38398268

RESUMEN

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is an underdiagnosed condition despite being one of the most common inherited disorders in adults that is associated with an increased risk of developing chronic obstructive pulmonary disease (COPD). The aim was to evaluate the frequency of performing AAT levels and associated factors in COPD patients in an audit conducted in 2021-2022, as well as to compare with a previous audit conducted in 2014-2015. METHODS: EPOCONSUL 2021 is a cross-sectional audit that evaluated the outpatient care provided to COPD patients in respiratory clinics in Spain based on available data from medical registries. RESULTS: 4225 patients with a diagnosis of COPD from 45 centers were audited in 2021. A total of 1670 (39.5%) patients underwent AAT determination. Being treated at a specialized COPD outpatient clinic (OR 1.88, p = 0.007), age ≤ 55 years old (OR 1.84, p = 0.007) and a FEV1 < 50% (OR 1.86, p < 0.001) were associated with a higher likelihood of being tested for AAT, while Charlson index ≥ 3 (OR 0.63, p < 0.001) and genotyping of AATD availability (OR 0.42, p < 0.001) showed a statistically significant negative association. The analysis of cases included in respiratory units that participated in both audits showed an increase in the proportion of cases with AAT serum level testing available (adjusted OR 2.81, p < 0.001). The percentage of individuals with serum AAT levels < 60 mg/dL (a severe AATD) was 4%. CONCLUSIONS: Our analysis identifies significant improvements in adherence to the recommendation to test AAT levels in COPD patients, performed in 4 out of 10 patients, being more likely at younger ages and with higher COPD severity, and with a detection of severe AATD of 4% among those tested, suggesting that clinicians still perform AAT testing in COPD patients selectively. Therefore, efforts are still needed to optimize AATD screening and establish new early detection strategies to reduce morbidity and mortality in these patients.

18.
ERJ Open Res ; 10(1)2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38410700

RESUMEN

Background: Exacerbations of COPD (ECOPD) have a major impact on patients and healthcare systems across the world. Precise estimates of the global burden of ECOPD on mortality and hospital readmission are needed to inform policy makers and aid preventive strategies to mitigate this burden. The aims of the present study were to explore global in-hospital mortality, post-discharge mortality and hospital readmission rates after ECOPD-related hospitalisation using an individual patient data meta-analysis (IPDMA) design. Methods: A systematic review was performed identifying studies that reported in-hospital mortality, post-discharge mortality and hospital readmission rates following ECOPD-related hospitalisation. Data analyses were conducted using a one-stage random-effects meta-analysis model. This study was conducted and reported in accordance with the PRISMA-IPD statement. Results: Data of 65 945 individual patients with COPD were analysed. The pooled in-hospital mortality rate was 6.2%, pooled 30-, 90- and 365-day post-discharge mortality rates were 1.8%, 5.5% and 10.9%, respectively, and pooled 30-, 90- and 365-day hospital readmission rates were 7.1%, 12.6% and 32.1%, respectively, with noticeable variability between studies and countries. Strongest predictors of mortality and hospital readmission included noninvasive mechanical ventilation and a history of two or more ECOPD-related hospitalisations <12 months prior to the index event. Conclusions: This IPDMA stresses the poor outcomes and high heterogeneity of ECOPD-related hospitalisation across the world. Whilst global standardisation of the management and follow-up of ECOPD-related hospitalisation should be at the heart of future implementation research, policy makers should focus on reimbursing evidence-based therapies that decrease (recurrent) ECOPD.

19.
Am J Hematol ; 99(4): 586-595, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38317420

RESUMEN

Blinatumomab is a BiTE® (bispecific T-cell engager) molecule that redirects CD3+ T-cells to engage and lyse CD19+ target cells. Here we demonstrate that subcutaneous (SC) blinatumomab can provide high efficacy and greater convenience of administration. In the expansion phase of a multi-institutional phase 1b trial (ClinicalTrials.gov, NCT04521231), heavily pretreated adults with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) received SC blinatumomab at two doses: (1) 250 µg once daily (QD) for week 1 and 500 µg three times weekly (TIW) thereafter (250 µg/500 µg) or (2) 500 µg QD for week 1 and 1000 µg TIW thereafter (500 µg/1000 µg). The primary endpoint was complete remission/complete remission with partial hematologic recovery (CR/CRh) within two cycles. At the data cutoff of September 15, 2023, 29 patients were treated: 14 at the 250 µg/500 µg dose and 13 at 500 µg/1000 µg dose. Data from two ineligible patients were excluded. At the end of two cycles, 12 of 14 patients (85.7%) from the 250 µg/500 µg dose achieved CR/CRh of which nine patients (75.0%) were negative for measurable residual disease (MRD; <10-4 leukemic blasts). At the 500 µg/1000 µg dose, 12 of 13 patients (92.3%) achieved CR/CRh; all 12 patients (100.0%) were MRD-negative. No treatment-related grade 4 cytokine release syndrome (CRS) or neurologic events (NEs) were reported. SC injections were well tolerated and all treatment-related grade 3 CRS and NEs responded to standard-of-care management, interruption, or discontinuation. Treatment with SC blinatumomab resulted in high efficacy, with high MRD-negativity rates and acceptable safety profile in heavily pretreated adults with R/R B-ALL.


Asunto(s)
Anticuerpos Biespecíficos , Antineoplásicos , Linfoma de Células B , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Humanos , Inducción de Remisión , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Anticuerpos Biespecíficos/efectos adversos , Linfoma de Células B/tratamiento farmacológico , Respuesta Patológica Completa , Enfermedad Aguda , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamiento farmacológico , Antineoplásicos/efectos adversos
20.
Animals (Basel) ; 14(3)2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38337999

RESUMEN

Bradypus variegatus has unique anatomical characteristics, and many of its vascular and digestive tract aspects have yet to be clearly understood. This lack of information makes clinical diagnoses and surgical procedures difficult. The aim of this study was to evaluate the anatomical aspects of frozen and glycerinated corpses of B. variegatus using computed tomography (CT), emphasizing vascular and digestive contrast studies. Nine corpses that died during routine hospital were examined via CT in the supine position with scanning in the craniocaudal direction. In frozen cadavers, the contrast was injected into a cephalic vein after thawing and, subsequently, was administered orally. In addition to bone structures, CT allowed the identification of organs, soft tissues, and vascular structures in specimens. Visualization of soft tissues was better after contrast been administered intravenously and orally, even without active vascularization. Furthermore, the surfaces of the organs were highlighted by the glycerination method. With this technique, it was possible to describe part of the vascularization of the brachial, cervical, thoracic, and abdominal regions, in addition to highlighting the esophagus and part of the stomach. CT can be another tool for the evaluation of B. variegatus cadavers by anatomists or pathologists, contributing to the identification of anatomical structures.

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