As the environments in which livestock are reared become more variable, animal robustness becomes an increasingly valuable attribute. Consequently, there is increasing focus on managing and breeding ...for it. However, robustness is a difficult phenotype to properly characterise because it is a complex trait composed of multiple components, including dynamic elements such as the rates of response to, and recovery from, environmental perturbations. In this review, the following definition of robustness is used: the ability, in the face of environmental constraints, to carry on doing the various things that the animal needs to do to favour its future ability to reproduce. The different elements of this definition are discussed to provide a clearer understanding of the components of robustness. The implications for quantifying robustness are that there is no single measure of robustness but rather that it is the combination of multiple and interacting component mechanisms whose relative value is context dependent. This context encompasses both the prevailing environment and the prevailing selection pressure. One key issue for measuring robustness is to be clear on the use to which the robustness measurements will employed. If the purpose is to identify biomarkers that may be useful for molecular phenotyping or genotyping, the measurements should focus on the physiological mechanisms underlying robustness. However, if the purpose of measuring robustness is to quantify the extent to which animals can adapt to limiting conditions then the measurements should focus on the life functions, the trade-offs between them and the animal’s capacity to increase resource acquisition. The time-related aspect of robustness also has important implications. Single time-point measurements are of limited value because they do not permit measurement of responses to (and recovery from) environmental perturbations. The exception being single measurements of the accumulated consequence of a good (or bad) adaptive capacity, such as productive longevity and lifetime efficiency. In contrast, repeated measurements over time have a high potential for quantification of the animal’s ability to cope with environmental challenges. Thus, we should be able to quantify differences in adaptive capacity from the data that are increasingly becoming available with the deployment of automated monitoring technology on farm. The challenge for future management and breeding will be how to combine various proxy measures to obtain reliable estimates of robustness components in large populations. A key aspect for achieving this is to define phenotypes from consideration of their biological properties and not just from available measures.
Mucosa-associated lymphoid tissue-derived (MALT) lymphoma, a low grade B-cell extranodal lymphoma, is the most frequent subset of primary pulmonary lymphoma. Our objective was to evaluate the initial ...extent of disease and to analyse the characteristics and long-term outcome of these patients. All chest and pathological departments of teaching hospitals in Paris were contacted in order to identify patients with a histological diagnosis of primary pulmonary lymphoma of the MALT subtype. 63 cases were identified. The median age was 60 yrs. 36% of cases had no symptoms at diagnosis. 46% of patients had at least one extrapulmonary location of lymphoma. The estimated 5- and 10-yr overall survival rates were 90% and 72%, respectively. Only two of the nine observed deaths were related to lymphoma. Age and performance status were the only two adverse prognostic factors for survival. Extrapulmonary location of lymphoma was not a prognostic factor for overall survival or for progression-free survival. Treatment with cyclophosphamide or anthracycline was associated with shorter progression-free survival, when compared with chlorambucil. The survival data confirm the indolent nature of pulmonary MALT lymphoma. Better progression-free survival was observed with chlorambucil when compared with cyclophosphamide or anthracycline.
Dementia with Lewy Bodies (DLB) is a common form of cognitive neurodegenerative disease. More than half of the patients affected are not or misdiagnosed because of the clinical similarity with ...Alzheimer's disease (AD), Parkinson's disease but also psychiatric diseases such as depression or psychosis. In this review, we evaluate the interest of different biomarkers in the diagnostic process: cerebrospinal fluid (CSF), brain MRI, FP-CIT SPECT, MIBG SPECT, perfusion SPECT, FDG-PET by focusing more specifically on differential diagnosis between DLB and AD. FP-CIT SPECT is of high interest to discriminate DLB and AD, but not at the prodromal stage. Brain MRI has shown differences in group study with lower grey matter concentration of the Insula in prodromal DLB, but its interest in clinical routine is not demonstrated. Among the AD biomarkers (t-Tau, phospho-Tau181, Aβ42 and Aβ40) used routinely, t-Tau and phospho-Tau181 have shown excellent discrimination whatever the clinical stages severity. CSF Alpha-synuclein assay in the CSF has also an interest in the discrimination between DLB and AD but not in segregation between DLB and healthy elderly subjects. CSF synuclein RT-QuIC seems to be an excellent biomarker but its application in clinical routine remains to be demonstrated, given the non-automation of the process.
Severe eosinophilic asthma (SEA) is associated with multiple exacerbations. Fractional exhaled nitric oxide (FeNO), a biomarker of airway T2 inflammation, is known to be correlated with the risk of ...exacerbations. While the use of FeNO is well established to predict the therapeutic response to dupilumab (anti-IL-4/IL-13), it remains uncertain for biologics targeting the IL-5 pathway.
We conducted an observational, retrospective, monocentric analysis of adults with SEA who started mepolizumab (anti-IL-5) or benralizumab (anti-IL-5R) between January 1, 2016 and December 31, 2020.
Data were collected for 109 patients. All participants reported uncontrolled asthma with a median of 3 annual exacerbations and a median Asthma Control Test score of 12. They all had an initial blood eosinophilia >300/mm
3
, with a median at 610/mm
3
(IQR 420-856). Patients with a baseline FeNO ≥50 ppb reported more exacerbations in the previous year than those with a FeNO <50 ppb (p = 0.02). After initiation of treatment, change in FeNO was not associated with therapeutic response. However, decrease in the annual number of exacerbations was significantly greater in patients with a baseline FeNO ≥50 ppb than in those with a baseline FeNO <50 ppb (-3.3 ± 2.7 vs −0.9 ± 2.4, respectively; p = 0.01). There was no association between baseline FeNO values and subsequent lung function, asthma control or reduction of oral corticosteroids use.
In this real-world cohort, adults with SEA who had a baseline FeNO ≥50 ppb experienced a greater decrease in exacerbations after 12 months of anti-IL-5 or IL-5R biologics than those with a FeNO <50 ppb.
Background
First-line treatment with FOLFIRINOX significantly increases overall survival (OS) in patients with metastatic pancreatic adenocarcinoma (PA) compared with gemcitabine. The aim of this ...observational cohort was to evaluate the tolerability and efficacy of this regimen in unresectable locally advanced PA (LAPA).
Patients and Methods
From February 2010 to February 2012, all consecutive patients from 11 French centers treated by FOLFIRINOX for a histologically proven LAPA were prospectively enrolled. Unresectability was defined independently by each center’s multidisciplinary staff at diagnosis. Absence of metastatic disease was confirmed by chest-abdomen-pelvis computed tomography scan. FOLFIRINOX was delivered every 2 weeks as previously reported until progressive disease, major toxicity, or consolidation treatment by radiotherapy and/or surgery.
Results
Seventy-seven patients were enrolled. They received a median number of five cycles (1–30). Grade 3–4 toxicities were neutropenia (11 %), nausea (9 %), diarrhea (6 %), fatigue (6 %), and anemia (1 %). Grade 2–3 sensory neuropathy occurred in 25 % of patients. No toxic death was reported and only 6 % of patients had to stop treatment because of toxicity. Disease control rate was 84 with 28 % of objective response (Response Evaluation Criteria in Solid Tumors). Seventy-five percent of patients received a consolidation therapy: 70 % had radiotherapy and 36 % underwent a surgical resection, with a curative intent. Within the whole cohort, 1-year OS rate was 77 % (95 % CI 65–86) and 1-year progression-free survival rate was 59 % (95 % CI 46–70).
Conclusion
First-line FOLFIRINOX for LAPA seems to be effective and have a manageable toxicity profile. These promising results will have to be confirmed in a phase III randomized trial.
Severe COVID-19 is associated with epithelial and endothelial barrier dysfunction within the lung as well as in distal organs. While it is appreciated that an exaggerated inflammatory response is ...associated with barrier dysfunction, the triggers of vascular leak are unclear. Here, we report that cell-intrinsic interactions between the Spike (S) glycoprotein of SARS-CoV-2 and epithelial/endothelial cells are sufficient to induce barrier dysfunction in vitro and vascular leak in vivo, independently of viral replication and the ACE2 receptor. We identify an S-triggered transcriptional response associated with extracellular matrix reorganization and TGF-β signaling. Using genetic knockouts and specific inhibitors, we demonstrate that glycosaminoglycans, integrins, and the TGF-β signaling axis are required for S-mediated barrier dysfunction. Notably, we show that SARS-CoV-2 infection caused leak in vivo, which was reduced by inhibiting integrins. Our findings offer mechanistic insight into SARS-CoV-2-triggered vascular leak, providing a starting point for development of therapies targeting COVID-19.
Allergic bronchopulmonary aspergillosis (ABPA) is a bronchopulmonary disease caused by a complex hypersensitivity to Aspergillus and is usually associated with underlying respiratory diseases such as ...asthma or cystic fibrosis. Mucus plugging can lead to segmental or lobar atelectasis, but complete lung atelectasis has been exceptionally reported in the literature, making it difficult to diagnose. The diagnosis of ABPA may however be suggested in patients without known predisposing respiratory disorder, even in the absence of other relevant radiographic findings.
We report five cases of total unilateral lung collapse secondary to ABPA in 70-81-year-old women. Two of them had a past history of ABPA, while total unilateral lung collapse was the first sign of the disease in the other three patients, contributing to the initial misdiagnosis. Flexible bronchoscopy was initially performed to remove mucus plugs from the obstructed airways but was inefficient in four cases. Corticosteroid and/or antifungal treatment was needed.
ABPA can cause total unilateral lung collapse even in patients without known underlying chronic respiratory disease, making the diagnosis difficult. Flexible bronchoscopy should be considered when lung collapse is associated with respiratory distress but corticosteroids are the mainstay treatment for ABPA.
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