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.

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.

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.

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.

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.

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.

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.

Phenotypic variation seems not to be associated with the genetic profile in Zygopetalum (Orchidaceae): a case study of a high-elevation rocky complex.

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.

Sternal cleft: new options for reconstruction.

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.

Randomized comparison of oblique and perpendicular stabilizers for minimally invasive repair of pectus excavatum.

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.

Single agent subcutaneous blinatumomab for advanced acute lymphoblastic leukemia.

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.

The immunopathological landscape of human pre-TCRα deficiency: From rare to common variants.

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.

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

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

Percepción de riesgo de contagio de la COVID-19 en estudiantes de una universidad estatal de Chile / COVID-19 risk perception among students at a state university in Chile

RESUMEN Objetivo: Evaluar el nivel de percepción de riesgo de contagio de la COVID-19 frente al retorno a las clases presenciales y analizar esta percepción con variables sociodemográficas y de salud asociadas a esta enfermedad. Materiales y métodos: Estudio transversal y prospectivo. Se adaptó el cuestionario para evaluar la percepción de riesgo de contagio de la COVID-19 (PCR-CV19) en 532 universitarios. Además, se realizó un análisis de asociación de las cuatro dimensiones del PCR-CV19 (vulnerabilidad cognitiva, vulnerabilidad emocional, conductas de riesgo-protección y gravedad) y el índice de percepción con variables sociodemográficas y de salud. Se utilizaron técnicas estadísticas: análisis de varianza (ANOVA) de una vía (OneWay ANOVA), previa verificación de la prueba de normalidad Shapiro-Wilk y la prueba de Levene para la homogeneidad y la prueba post-hoc de Tukey o Ganes-Howell. Estos análisis se realizaron en el programa estadístico JAMOVI, versión 1.2.2. Resultados: Se evidenció un nivel moderado de percepción de riesgo de contagio, en donde las dimensiones de las conductas de riesgo-protección y gravedad se identificaron como las más relevantes; asimismo, se encontró asociación entre las dimensiones del PCR-CV19 y el índice de percepción con las variables edad, género, consumo de alcohol e indicadores de salud física y mental (ansiedad y depresión) y las experiencias vividas con la enfermedad de la COVID-19. Los aspectos de vulnerabilidad cognitiva y emocional fueron las dimensiones más sensibles en la evaluación de la percepción. Conclusiones: Seguimos enfrentando condiciones de riesgo que surgen de manera constante, lo que hace necesario mantener un esquema de vigilancia de la percepción de riesgo que experimenta la población. En los universitarios, los aspectos de vulnerabilidad cognitiva y emocional fueron las dimensiones más sensibles en la evaluación de la percepción del riesgo y las experiencias vividas con la COVID-19 (enfermedad o muerte). El hecho de que los universitarios no se sientan vulnerables y/o no perciban la gravedad asociada al contagio puede afectar sus conductas de autocuidado. Estos resultados tienen implicaciones claves para la salud pública, por lo que se requiere un abordaje intersectorial, con el objetivo de contar con información relevante para enfrentar futuras pandemias.

ABSTRACT Objective: To evaluate the level of COVID-19 risk perception (PCR-CV19) by returning to in-person classes and to analyze this perception with sociodemographic and health variables associated with such disease. Materials and methods: A cross-sectional and prospective study. The questionnaire was adapted to assess the PCR-CV19 among 532 university students. Moreover, an association analysis of the four dimensions of the PCR-CV19 (cognitive vulnerability, emotional vulnerability, risky-protective behaviors and severity) and the perception index was performed with sociodemographic and health variables. The following statistical methods were used: one-way analysis of variance (ANOVA), Shapiro-Wilk test for normality, Levene's test for homogeneity of variances and Tukey's honest significant difference or Games-Howell post hoc tests. These analyses were performed using the Jamovi statistical software, version 1.2.2. Results: A moderate level of PCR-CV19 was found, where the most relevant dimensions were risky-protective behaviors and severity. In addition, there was an association between the dimensions PCR-CV19 and perception index with the variables age, gender, alcohol consumption, physical and mental health indicators (anxiety and depression), and experiences with COVID-19. Cognitive vulnerability and emotional vulnerability were the most sensitive dimensions in the evaluation of the PCR-CV19. Conclusions: We continue to face constant risk conditions, thus making it necessary to maintain a surveillance scheme of the PCR-CV19 experienced by the population. In university students, cognitive vulnerability and emotional vulnerability were the most sensitive dimensions in the evaluation of PCR-CV19 and experiences with COVID-19 (illness or death). The fact that university students do not feel vulnerable and/or do not perceive the severity associated with COVID-19 transmission may affect their self-care behaviors. These results have key implications for public health; therefore, an intersectoral approach is required to have relevant information in order to face future pandemics.

CD8+ Treg cells play a role in the obesity-associated insulin resistance.

Obesity-related chronic low-grade inflammation may trigger insulin resistance and type 2 diabetes (T2D) development. Cells with regulatory phenotype have been shown to be reduced during obesity, especially CD4+ Treg cells. However, little is known about the CD8+ Treg cells. Therefore, we aim to characterize the CD8+ Treg cells in human peripheral blood and adipose tissue, specifically, to address the effect of obesity and insulin resistance in this regulatory immune cell population. A group of 42 participants with obesity (OB group) were recruited. Fourteen of them were evaluated pre- and post-bariatric surgery. A group of age- and sex-matched healthy volunteers (n = 12) was also recruited (nOB group). CD8+ Treg cell quantification and phenotype were evaluated by flow cytometry, in peripheral blood (PB), subcutaneous (SAT), and visceral adipose tissues (VAT). The OB group displayed a higher percentage of CD8+ Treg cells in PB, compared to the nOB. In addition, they were preferentially polarized into Tc1- and Tc1/17-like CD8+ Treg cells, compared to nOB. Moreover, SAT displayed the highest content of CD8+ Tregs infiltrated, compared to PB or VAT, while CD8+ Tregs infiltrating VAT displayed a higher percentage of cells with Tc1-like phenotype. Participants with pre-diabetes displayed a reduced percentage of TIM-3+CD8+ Tregs in circulation, and PD-1+CD8+ Tregs infiltrated in the VAT. An increase in the percentage of circulating Tc1-like CD8+ Treg cells expressing PD-1 was observed post-surgery. In conclusion, obesity induces significant alterations in CD8+ Treg cells, affecting their percentage and phenotype, as well as the expression of important immune regulatory molecules.

Incidence, risk factors, and outcomes of second neoplasms in patients with acute promyelocytic leukemia: the PETHEMA-PALG experience.

The most important challenges in acute promyelocytic leukemia (APL) is preventing early death and reducing long-term events, such as second neoplasms (s-NPLs). We performed a retrospective analysis of 2670 unselected APL patients, treated with PETHEMA "chemotherapy based" and "chemotherapy free" protocols. Only de novo APL patients who achieved complete remission (CR) and completed the three consolidation cycles were enrolled into the analysis. Out of 2670 APL patients, there were 118 (4.4%) who developed s-NPLs with the median latency period (between first CR and diagnosis of s-NPL) of 48.0 months (range 2.8-231.1): 43.3 (range: 2.8-113.9) for s-MDS/AML and 61.7 (range: 7.1-231.1) for solid tumour. The 5-year CI of all s-NPLs was of 4.43% and 10 years of 7.92%. Among s-NPLs, there were 58 cases of s-MDS/AML, 3 cases of other hematological neoplasms, 57 solid tumours and 1 non-identified neoplasm. The most frequent solid tumour was colorectal, lung and breast cancer. Overall, the 2-year OS from diagnosis of s-NPLs was 40.6%, with a median OS of 11.1 months. Multivariate analysis identified age of 35 years (hazard ratio = 0.2584; p < 0.0001) as an independent prognostic factor for s-NPLs. There were no significant differences in CI of s-NPLs at 5 years between chemotherapy-based vs chemotherapy-free regimens (hazard ratio = 1.09; p = 0.932). Larger series with longer follow-up are required to confirm the potential impact of ATO+ATRA regimens to reduce the incidence of s-NPLs after front-line therapy for APL.

Untargeted Metabolomic Study of Lung Cancer Patients after Surgery with Curative Intent.

Lung cancer (LC) is a leading cause of mortality, claiming more than 1.8 million deaths per year worldwide. Surgery is one of the most effective treatments when the disease is in its early stages. The study of metabolic alterations after surgical intervention with curative intent could be used to assess the response to treatment or the detection of cancer recurrence. In this study, we have evaluated the metabolomic profile of serum samples (n = 110) from preoperative (PRE) and postoperative (POST) LC patients collected at two different time points (1 month, A; 3-6 months, B) with respect to healthy people. An untargeted metabolomic platform based on reversed phase (RP) and hydrophilic interaction chromatography (HILIC), using ultra-high performance liquid chromatography (UHPLC) and mass spectrometry (MS), was applied (MassIVE ID MSV000092213). Twenty-two altered metabolites were annotated by comparing all the different studied groups. DG(14,0/22:1), stearamide, proline, and E,e-carotene-3,3'-dione were found altered in PRE, and their levels returned to those of a baseline control group 3-6 months after surgery. Furthermore, 3-galactosyllactose levels remained altered after intervention in some patients. This study provides unique insights into the metabolic profiles of LC patients after surgery at two different time points by combining complementary analytical methods.