The key role of sufficiency for low demand-based carbon neutrality and energy security across Europe.

A detailed assessment of a low energy demand, 1.5 ∘C compatible pathway is provided for Europe from a bottom-up, country scale modelling perspective. The level of detail enables a clear representation of the potential of sufficiency measures. Results show that by 2050, 50% final energy demand reduction compared to 2019 is possible in Europe, with at least 40% of it attributable to various sufficiency measures across all sectors. This reduction enables a 77% renewable energy share in 2040 and 100% in 2050, with very limited need for imports from outside of Europe and no carbon sequestration technologies. Sufficiency enables increased fairness between countries through the convergence towards a more equitable share of energy service levels. Here we show, that without sufficiency measures, Europe misses the opportunity to transform energy demand leaving considerable pressure on supply side changes combined with unproven carbon removal technologies.

Predictors of postoperative complications after sternectomy on oncologic patients.

BACKGROUND: Chest wall tumors are uncommon. The surgical objective is local disease control and the relief of symptoms. Due to the heterogeneity of cases, the great variety of reconstructions, size of resection, and clinical and surgical outcomes are still uncertain. METHODS: Patients were submitted to sternectomies for tumors between 1997 and 2019. Oncological, and surgical characteristics were taken into consideration. The outcomes were related to the size of resection and classified into local and systemic complications. The authors used univariate and multivariate analyses to determine predictors of complications. Survival analysis and Kaplan-Meier curves were obtained. RESULTS: Thirty resections were performed due to metastatic disease. Partial sternectomy was accomplished in 48.8 %, followed by subtotal in 40 %. Primary closure using Pectoralis major was performed in 48.8 %, and Latissimus dorsi in 35.5 %. Polypropylene mesh was used in 86.6 % of reconstructions. The prosthesis removal was necessary in 6.66 %. Respiratory failure was evidenced in 6.66 %. The resection area was a predictor of local and systemic complications (p = 0.0029; p = 0.0004 respectively) in univariate analysis. However, the size of resection was the only predictor of systemic complications regarding multivariate analysis (p = 0.014, 95 % CI 1.00‒1.07). CONCLUSION: The size of the resection was related to systemic complications, and the mesh reconstruction resulted in a low percentage of prosthesis removal and respiratory failure. This suggests a high resistance to local issues and a low respiratory failure rate.

Evaluation of the Importance of Capsule Transparency in Dry Powder Inhalation Devices.

The aim of this work is to test whether the use of a transparent capsule affects the residual capsule weight after inhalation as a surrogate of the inhaled delivered dose for patients with non-reversible chronic airway disease. Researchers conducted an observational cross-sectional study with patients using a single-dose dry powder inhaler. The weight of the capsule was measured with a precision microbalance before and after inhalation. Ninety-one patients were included, of whom 63 (69.2%) used a transparent capsule. Inhalation with a transparent capsule achieved a weight decrease of 30.1% vs 8.6% for devices with an opaque capsule (P <0.001). These data reinforce the need to provide patients with mechanisms that verify the correct inhalation technique.

Animal Model of Autism Induced by Valproic Acid Combined with Maternal Deprivation: Sex-Specific Effects on Inflammation and Oxidative Stress.

Autism spectrum disorder (ASD) etiology probably involves a complex interplay of both genetic and environmental risk factors, which includes pre- and perinatal exposure to environmental stressors. Thus, this study evaluated the effects of prenatal exposure to valproic acid (VPA) combined with maternal deprivation (MD) on behavior, oxidative stress parameters, and inflammatory state at a central and systemic level in male and female rats. Pregnant Wistar rats were exposed to VPA during gestation, and the offspring were submitted to MD. Offspring were tested for locomotor and social behavior; rats were euthanized, where the cerebellum, posterior cortex, prefrontal cortex, and peripheric blood were collected for oxidative stress and inflammatory analysis. It was observed that young rats (25-30 days old) exposed only to VPA presented a lower social approach when compared to the control group. VPA + MD rats did not present the same deficit. Female rats exposed to VPA + MD presented oxidative stress in all brain areas analyzed. Male rats in the VPA and VPA + MD groups presented oxidative stress only in the cerebellum. Regarding inflammatory parameters, male rats exposed only to MD exhibited an increase in pro-inflammatory cytokines in the blood and in the cortex total. The same was observed in females exposed only to VPA. Animals exposed to VPA + MD showed no alterations in the cytokines analyzed. In summary, gestational (VPA) and perinatal (MD) insults can affect molecular mechanisms such as oxidative stress and inflammation differently depending on the sex and brain area analyzed. Combined exposition to VPA and MD triggers oxidative stress especially in female brains without evoking an inflammatory response.

Similarities and differences between systemic juvenile idiopathic arthritis and adult-onset Still's disease: a multicenter Spanish study.

To describe the characteristics of systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD), compare their presentation and evolution, and analyse possible complication predictors. Multicenter study. Data were retrieved from a hospital-based study of patients with a diagnosis or suspected diagnosis of sJIA or AOSD according to the responsible physician and followed-up for at least one year. Descriptive variables (classification criteria, clinical manifestations, complications, family, and personal history) were collected at disease onset and during follow-up. We present the clinical characteristics of 326 patients, 67% of whom had a diagnosis of sJIA and 33% of AOSD. Clinical manifestation frequencies were similar between the two groups, except for odynophagia, which was significantly more frequent in AOSD than in sJIA (78.4% vs. 25.5%; p < 0.0001). Among the complications, macrophage activation syndrome (MAS) was significantly more common in sJIA than in AOSD (24.4% vs. 9.5%; p = 0.002), to the extent that an sJIA diagnosis significantly increased the risk of MAS, together with serositis presence, and the need for biological therapy. Patients with sJIA and AOSD showed similar characteristics, supporting the idea that they are both part of Still's disease, but are expressed at different ages. Differences in manifestations and complications might be due to different management between diseases and immune response maturity.

Lymphatic Regeneration after Popliteal Lymph Node Excision and Implantation of Aligned Nanofibrillar Collagen Scaffolds: An Experimental Rabbit Model.

Lymphedema presents significant challenges to patients' quality of life, prompting the exploration of innovative treatments, such as collagen scaffolds, aimed at treating and reducing the risk of lymphedema. We aimed to evaluate the preventive and therapeutic efficacy and the lymphangiogenic potential of implanted aligned nanofibrillar collagen scaffolds (BioBridgeTM) following the induction of secondary lymphedema in a rabbit model. Thirty rabbits were divided into treatment (G1), prevention (G2), and control (G3) groups. Secondary lymphedema was induced in all groups. BioBridgeTM implantation was performed in G2 and G1 on days 0 and 60, respectively. Follow-ups included hindlimb circumference measurements and indocyanine green lymphography at 0, 60, and 90 days. None of the study rabbits exhibited dermal backflow on day 0 before surgery. At 60 days, the incidence rates of dermal backflow in G1, G2, and G3 were 100%, 44.4%, and 90%, respectively. Furthermore, at 90 days, the incidence rates were 22.2%, 44.4%, and 90%, respectively. New linear lymphatic observation was seen in rabbits with resolved dermal backflow. The findings of this study demonstrated the capacity of BioBridgeTM scaffolds to induce new lymphatic vessel formation and reduce dermal backflow in secondary lymphedema in a rabbit model.

A Pilot Study on Proteomic Predictors of Mortality in Stable COPD.

Chronic Obstructive Pulmonary Disease (COPD) is the third leading cause of global mortality. Despite clinical predictors (age, severity, comorbidities, etc.) being established, proteomics offers comprehensive biological profiling to obtain deeper insights into COPD pathophysiology and survival prognoses. This pilot study aimed to identify proteomic footprints that could be potentially useful in predicting mortality in stable COPD patients. Plasma samples from 40 patients were subjected to both blind (liquid chromatography-mass spectrometry) and hypothesis-driven (multiplex immunoassays) proteomic analyses supported by artificial intelligence (AI) before a 4-year clinical follow-up. Among the 34 patients whose survival status was confirmed (mean age 69 ± 9 years, 29.5% women, FEV1 42 ± 15.3% ref.), 32% were dead in the fourth year. The analysis identified 363 proteins/peptides, with 31 showing significant differences between the survivors and non-survivors. These proteins predominantly belonged to different aspects of the immune response (12 proteins), hemostasis (9), and proinflammatory cytokines (5). The predictive modeling achieved excellent accuracy for mortality (90%) but a weaker performance for days of survival (Q2 0.18), improving mildly with AI-mediated blind selection of proteins (accuracy of 95%, Q2 of 0.52). Further stratification by protein groups highlighted the predictive value for mortality of either hemostasis or pro-inflammatory markers alone (accuracies of 95 and 89%, respectively). Therefore, stable COPD patients' proteomic footprints can effectively forecast 4-year mortality, emphasizing the role of inflammatory, immune, and cardiovascular events. Future applications may enhance the prognostic precision and guide preventive interventions.

Contribution of copy number to improve risk stratification of adult T-cell acute lymphoblastic leukemia patients enrolled in measurable residual disease-oriented trials.

Not available.

Whole genome sequencing enhances molecular diagnosis of primary ciliary dyskinesia.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a genetic disorder affecting motile cilia. Most cases are inherited recessively, due to variants in >50 genes that result in abnormal or absent motile cilia. This leads to chronic upper and lower airway disease, subfertility, and laterality defects. Given overlapping clinical features and genetic heterogeneity, diagnosis can be difficult and often occurs late. Of those tested an estimated 30% of genetically screened PCD patients still lack a molecular diagnosis. A molecular diagnosis allows for appropriate clinical management including prediction of phenotypic features correlated to genotype. Here, we aimed to identify how readily a genetic diagnosis could be made using whole genome sequencing (WGS) to facilitate identification of pathogenic variants in known genes as well as novel PCD candidate genes. METHODS: WGS was used to screen for pathogenic variants in eight patients with PCD. RESULTS: 7/8 cases had homozygous or biallelic variants in DNAH5, DNAAF4 or DNAH11 classified as pathogenic or likely pathogenic. Three identified variants were deletions, ranging from 3 to 13 kb, for which WGS identified precise breakpoints, permitting confirmation by Sanger sequencing. WGS yielded identification of a de novo variant in a novel PCD gene TUBB4B. CONCLUSION: Here, WGS uplifted genetic diagnosis of PCD by identifying structural variants and novel modes of inheritance in new candidate genes. WGS could be an important component of the PCD diagnostic toolkit, increasing molecular diagnostic yield from current (70%) levels, and enhancing our understanding of fundamental biology of motile cilia and variants in the noncoding genome.

Incidence and recurrence of bovine abortion in dairy cattle from Costa Rica.

The reproductive efficiency and milk yield of cows are crucial factors in a dairy farm's profitability. However, abortions can have a negative impact on these factors. While the morbidity of abortion has been estimated in many countries, information on the burden on dairy cattle in tropical conditions is limited, and Costa Rica is a good example. This study aims to assess the incidence and recurrence of bovine abortion in dairy cattle from Costa Rica. The study analysed the morbidity of abortion in Costa Rican dairy herds between 2010 and 2022. The incidence rate (IR) and the recurrence rate (ReR) were calculated per 100 cow-months at risk using data from the Veterinary Automated Management and Production Control Programme (VAMPP). The dataset comprised 1032,457 lactations from 330,265 cows in 1134 specialized dairy herds. Abortions were classified either as early foetal mortality (EFM) or late foetal mortality (LFM). Rates were estimated based on cow breed, lactation number, and ecological zone to which the farm belongs. The IR of general abortion, EFM, and LFM cases were 0.98, 0.41, and 0.57 per 100 cow-months at risk, respectively. No statistically significant differences were found in the IR between cow breed, lactation number, and ecological zone, nor for the trend of abortions over calving years. The first ReR (for cows that had one previous abortion during the lactation) was 0.95, and the second ReR (for cows that had two previous abortions during the lactation) was 1.41 per 100 cow-months at risk. These results suggest that bovine abortions are an important ongoing problem in dairy farms in Costa Rica with potentially detrimental effects on the reproductive and productive performance of cows and may be representative of other specialized tropical dairy systems in Latin America.

Dysregulated STAT3 signaling and T cell immunometabolic dysfunction define a targetable, high mortality subphenotype of critically ill children.

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.

Sex-Differences in Alpha-1 Antitrypsin Deficiency: Data From the EARCO Registry.

BACKGROUND: Sex and gender influence many aspects of chronic obstructive pulmonary disease (COPD). Limited data are available on this topic in alpha-1 antitrypsin deficiency (AATD). We therefore aimed to investigate sex issues in the EARCO registry, a prospective, international, observational cohort study. METHODS: Baseline data from PiZZ individuals, enrolled in the registry with complete data on sex and smoking history were analysed by group comparisons and binary logistic regression analyses. RESULTS: 1283 patients with AATD, 49.3% women were analysed. Females reported less tobacco consumption (16.8±12.2 vs. 19.6±14.5 PY, p=0.006), occupational exposures towards gases, dusts or asbestos (p<0.005 each) and consumed less alcohol (5.5±7.6 vs. 8.4±10.3u/week, p<0.001). Females reported COPD (41% vs. 57%, p<0.001) and liver disease (11% vs. 20%, p<0.001) less often. However, they had a higher prevalence of bronchiectasis (24% vs. 13%, p<0.001). Despite better lung function (FEV1%pred. 73.6±29.9 vs. 62.7±29.5, p<0.001) females reported a similar symptom burden (CAT 13.4±9.5 vs. 12.5±8.9, p=ns) and exacerbation frequency (at least one in the previous year 30% vs. 26%, p=ns) compared to males. In multivariate analyses, female sex was an independent risk factor for exacerbations in the previous year OR 1.6 p=0.001 in addition to smoking history, COPD, asthma and bronchiectasis and was also identified as risk factors for symptom burden (CAT≥10) OR 1.4 p=0.014 besides age, BMI, COPD and smoking history. CONCLUSION: Men had higher rates of COPD and liver disease, women were more likely to have bronchiectasis. Women's higher symptom burden and exacerbation frequency suggest they may need tailored treatment approaches.

Estudo qualitativo sobre as políticas de saúde mental no município de Santo André (SP) / Qualitative study on mental health policies in Santo André city / Estudio cualitativo sobre las políticas de salud mental en la ciudad de Santo André, São Paulo

Esta pesquisa, de caráter qualitativo, procura compreender os movimentos de avanços e recuos pelos quais as políticas de saúde mental de Santo André (SP) passaram recentemente, época na qual a visão da Reforma Psiquiátrica e da sua contrarreforma se conflitaram. Seguindo essa proposta, após revisão de literatura na qual se reflete sobre as disputas em torno do conceito de saúde mental, a trajetória histórica dessas políticas no Brasil e no município, foram realizadas três entrevistas semiestruturadas com profissionais da área que atuam na região: a tomadora de decisão, um gerente de equipamento e um trabalhador de ponta. Tais entrevistas foram gravadas, transcritas e divididas em eixos de análise, dos quais extraiu-se que, de forma geral, tanto do ponto de vista federal quanto estadual, houve ataques à Reforma Psiquiátrica e às políticas dela oriundas, seja pela falta de financiamento, seja pela promoção de outras perspectivas de mundo a respeito do significado do adoecimento mental e sua forma de tratamento e que acabou por afetar o andamento dos serviços a nível local, cujo sucateamento só não foi maior pelo apoio do Executivo do município, dos trabalhadores e do próprio histórico de construção dos serviços.

This qualitative research seeks to understand the advance and setback dynamics that public mental health policies in Santo André city, São Paulo, have recently undergone, a time in which Psychiatric Reform and its counter-reform conflicted. After a literature review on the disputes surrounding the concept of mental health, the historical trajectory of these policies in Brazil and in the municipality, we conducted three semi-structured interviews with professionals in the field: a policy decision-maker, an equipment manager and a frontline worker. These interviews were recorded, transcribed in full and divided into axes of analysis. Results showed that both from a federal and state government point of view, there were attacks on the Psychiatric Reform and its policies whether due to lack of funding or promotion of other worldviews regarding the meaning of mental illness and its treatment which affected the progress of services at the local level, the scrapping of which was only mitigated by the support of the municipality's Executive, workers and the service's construction history.

Esta investigación cualitativa buscó comprender los movimientos de avances y retrocesos que las políticas públicas de salud mental han experimentado recientemente en Santo André (São Paulo, Brasil), un momento en el que la visión de la reforma psiquiátrica y su contrarreforma entraron en conflicto. En esta propuesta, luego de una revisión de la literatura que reflexiona sobre las disputas en torno al concepto de salud mental, la trayectoria histórica de esas políticas en Brasil y en el municipio, se realizaron tres entrevistas semiestructuradas a profesionales del área que actúan en el región: el tomador de decisiones, un administrador de equipos y un trabajador de primera línea. Estas entrevistas fueron grabadas para su posterior transcripción y división en ejes de análisis; de los cuales se concluyó que, en general, tanto desde el punto de vista federal como estatal hubo ataques a la reforma psiquiátrica y las políticas que de ella se derivan, ya sea por falta de financiación o por la promoción de otras miradas sobre el significado de la enfermedad mental y su forma de tratamiento, lo que terminó afectando la marcha de los servicios a nivel local, cuyo desguace solo se vio agravado por el apoyo del Ejecutivo del municipio, de los trabajadores y del propio historial de construcción del servicio.

Trends in lung cancer incidence in Spain (1990-2019): insights from Global Burden of Diseases data.

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.

Management of soft tissue sarcomas of the chest wall: a comprehensive overview.

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.

Lymphatic Patterns in the Superficial Circumflex Iliac Artery Perforator Flap.

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.

Risk of lung disease in the PI*SS genotype of alpha-1 antitrypsin: an EARCO research project.

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).

Triple Therapy and Clinical Control in B+ COPD Patients: A Pragmatic, Prospective, Randomized Trial.

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.

Lymphaticovenous anastomosis in rabbits: A novel live experimental animal model for supermicrosurgical training.

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.