Anatomical segmentectomy versus pulmonary lobectomy for stage I non-small-cell lung cancer: patients selection and outcomes from the European Society of Thoracic Surgeons database analysis

OBJECTIVES The aims of this study were to describe the potential selection criteria for patients scheduled for lobectomy versus segmentectomy for stage I non-small-cell lung cancer and to compare the 2 procedures in terms of intraoperative variables and postoperative outcomes using the European Society of Thoracic Surgeons (ESTS) Registry.Open in a separate windowMETHODSThis observational multicentre retrospective cross-sectional study was based on data collected from the ESTS database. The following were set as inclusion criteria: pulmonary lobectomy or segmentectomy for stage I primary lung cancer (according to 8th TNM edition), no previous lung surgery and no induction chemotherapy or radiotherapy. Statistical significance was examined using Mann–Whitney or 2 proportions Z tests.RESULTSAmong 63 542 patients enrolled in the ESTS database (2007–2018), 17 692 met the inclusion criteria: 15 845 patients received lobectomy and 1847 segmentectomy. Video-assisted thoracic surgery (VATS) lobectomy and VATS segmentectomy were the 27.8% and 31.9% of the procedures, respectively. Lobectomy group was significantly younger and had a lower American Society of Anaesthesiology (ASA) score, lower comorbidities prevalence and better respiratory function. The segmentectomy group had lower complications rate (25.6% vs 33.8%). When considering only the last 5 years, ASA score was similar between the 2 groups, although pulmonary function remained significantly lower in the segmentectomy group.CONCLUSIONSAccording to the ESTS database, segmentectomy was preferably offered to ‘compromised’ patients, with limited respiratory function, higher ASA score and relevant comorbidities. Nevertheless, the procedure showed lower complications rate and similar short-term outcomes compared to lobectomy. During the last 5 years, segmentectomy appeared to be regarded as a valid alternative, even for selected patients who could tolerate both procedures.     

Quantification of branching within high molecular weight polymers with polyester backbones formed by transfer-dominated branching radical telomerisation (TBRT)

New branched polymerisations offer previously inaccessible macromolecules and architectural understanding is important as it provides insight into the branching mechanism and enables the determination of structure–property relationships. Here we present a detailed inverse gated ¹³C NMR characterisation of materials derived from the very recently reported Transfer-dominated Branching Radical Telomerisation (TBRT) approach to quantify branching and provide an insight into cyclisation.

The characterisation and quantification of branching is key to understanding new complex macromolecules. Here we establish approaches to evaluate the unique and novel architectures formed by Transfer-dominated Branching Radical Telomerisation (TBRT).     

Biasing human epidermal growth factor receptor 4 (HER4) tyrosine kinase signaling with antibodies: Induction of cell death by antibody‐dependent HER4 intracellular domain trafficking

Human epidermal growth factor receptor 4 (HER4) isoforms have oncogenic or tumor suppressor functions depending on their susceptibility to proteolytic cleavage and HER4 intracellular domain (4ICD) translocation. Here, we report that the neuregulin 1 (NRG1) tumor suppressor mechanism through the HER4 JMa/CYT1 isoform can be mimicked by the agonist anti‐HER4 Ab C6. Neuregulin 1 induced cleavage of poly(ADP‐ribose) polymerase (PARP) and sub‐G₁ DNA fragmentation, and also reduced the metabolic activity of HER3^?/HER4⁺ cervical (C‐33A) and ovarian (COV318) cancer cells. This effect was confirmed in HER4 JMa/CYT1‐, but not JMa/CYT2‐transfected BT549 triple‐negative breast cancer cells. Neuregulin 1 favored 4ICD cleavage and retention in mitochondria in JMa/CYT1‐transfected BT549 cells, leading to reactive oxygen species (ROS) production through mitochondrial depolarization. Similarly, the anti‐HER4 Ab C6, which binds to a conformational epitope located on a.a. 575‐592 and 605‐620 of HER4 domain IV, induced 4ICD cleavage and retention in mitochondria, and mimicked NRG1‐mediated effects on PARP cleavage, ROS production, and mitochondrial membrane depolarization in cancer cells. In vivo, C6 reduced growth of COV434 and HCC1187 tumor cell xenografts in nude mice. Biasing 4ICD trafficking to mitochondria with anti‐HER4 Abs to mimic NRG1 suppressor functions could be an alternative anticancer strategy.     

Sequence-based human leukocyte antigen-B typing of patients infected with Ebola virus in Uganda in 2000: identification of alleles associated with fatal and nonfatal disease outcomes

The Sudan species of Ebola virus (SEBOV) causes severe, often fatal infection in approximately 50% of infected humans. We sought to determine whether the human leukocyte antigen-B (HLA-B) locus has a role in the outcome of SEBOV disease by typing 77 cases from an outbreak in northern Uganda in 2000-2001. Sequence-based HLA-B typing was performed using leukocytes isolated from 77 patients. Statistical analysis and a predictive discriminant analysis (PDA) were applied to typing data. Epitope prediction software was also applied to SEBOV sequences. Statistically significant associations were found between certain sets of alleles and either fatal or nonfatal disease outcomes. Alleles B*67 and B*15 were associated with fatal outcomes, whereas B*07 and B*14 were associated with nonfatal outcomes. The PDA-derived functions that were produced were 81.8% accurate in classifying patients into their correct outcome group. Several epitopes predicted to bind strongly to HLA-B*07 molecules were identified in the viral polymerase, nucleoprotein, and VP35 protein. HLA-B alleles associated with either fatal or nonfatal outcomes of SEBOV disease were identified and can be used in a predictive model. Studies of HLA-B-restricted epitopes could contribute to characterization of protective host responses and to vaccine development.     

Calcium consumption and insulin resistance syndrome parameters. Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR)

Background and aimA number of studies have investigated the role of dietary calcium in lipid metabolism and weight regulation, and the influence of dairy products on the incidence of insulin resistance syndrome. In this study we have examined the relationship between dietary calcium and the established parameters of the insulin resistance syndrome.Methods and resultsThe study population (n = 4372) was taken from the DESIR (Data from the Epidemiological Study on the Insulin Resistance Syndrome) cohort. Data for parameters relating to the syndrome were recorded, including glucose, serum insulin, triglycerides, HDL-cholesterol, waist circumference and blood pressure. Total energy, calcium and alcohol intake were estimated using a food-frequency questionnaire. Relationships between dietary calcium density and the above parameters were analyzed by multiple linear regression models, adjusted for age, smoking, alcohol consumption and physical activity. From one quartile of calcium density to the next, mean systolic and diastolic blood pressures and insulin concentrations decreased in women by 0.9 mmHg, 0.5 mmHg and 2.4%, respectively, and HDL-cholesterol increased by 0.007 mmol/l (all p < 0.05) after adjustment for age, smoking, alcohol intake and physical activity. In men, there was an increase of 0.2 kg/m² in the body mass index(BMI) and a decrease of 0.4 mmHg in diastolic blood pressure (both p < 0.05).ConclusionsThese results confirm a beneficial association between dietary calcium and arterial blood pressure, insulin and HDL-cholesterol levels in women, whereas in men there was only a beneficial association with diastolic blood pressure.