Elevated circulating metalloproteinase 7 predicts recurrent cardiovascular events in patients with carotid stenosis: a prospective cohort study

Background: Major adverse cardiovascular events are the main cause of morbidity and mortality over the long term in patients undergoing carotid endarterectomy. There are few reports assessing the prognostic value of markers of inflammation in relation to the risk of cardiovascular disease after carotid endarterectomy. Here, we aimed to determine whether matrix metalloproteinases (MMP-1, MMP-2, MMP-7, MMP-9 and MMP-10), tissue inhibitor of MMPs (TIMP-1) and in vivo inflammation studied by 18F-FDG-PET/CT predict recurrent cardiovascular events in patients with carotid stenosis who underwent endarterectomy. Methods: This prospective cohort study was carried out on 31 consecutive patients with symptomatic (23/31) or asymptomatic (8/31) severe (> 70%) carotid stenosis who were scheduled for carotid endarterectomy between July 2013 and March 2016. In addition, 26 healthy controls were included in the study. Plasma and serum samples were collected 2 days prior to surgery and tested for MMP-1, MMP-2, MMP-7, MMP-9, MMP-10, TIMP-1, high-density lipoprotein, low-density lipoprotein, high-sensitivity C-reactive protein and erythrocyte sedimentation rate. 18F-FDGPET/CT focusing on several territories’ vascular wall metabolism was performed on 29 of the patients because of no presurgical availability in 2 symptomatic patients. Histological and immunohistochemical studies were performed with antibodies targeting MMP-10, MMP-9, TIMP-1 and CD68. Results: The patients with carotid stenosis had significantly more circulating MMP-1, MMP-7 and MMP-10 than the healthy controls. Intraplaque TIMP-1 was correlated with its plasma level (r = 0.42 P = .02) and with 18F-FDG uptake (r = 0.38 P = .05). We did not find any correlation between circulating MMPs and in vivo carotid plaque metabolism assessed by 18F-FDG-PET. After a median follow-up of 1077 days, 4 cerebrovascular, 7 cardiovascular and 11 peripheral vascular events requiring hospitalization were registered. Circulating MMP-7 was capable of predicting events over and above the traditional risk factors (HR = 1.15 P = .006). When the model was associated with the variables of interest, the risk predicted by 18F-FDG-PET was not significant. Conclusions: Circulating MMP-7 may represent a novel marker for recurrent cardiovascular events in patients with moderate to severe carotid stenosis. MMP-7 may reflect the atherosclerotic burden but not plaque inflammation in this specific vascular territory

Results of A Phase 1 study of the oncolytic adenovirus DNX-2401 with radiotherapy for newly diagnosed diffuse intrinsic pontine glioma (DIPG)

Background A Phase 1, single center study is ongoing to evaluate the conditionally replicative oncolytic adenovirus, DNX-2401 (tasadenoturev), followed by radiotherapy (RT) in pediatric patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG). Methods Patients 1–18 years with newly diagnosed DIPG with no prior treatment, Lansky/Karnofsky performance score ≥ 70, and adequate organ function were enrolled. A tumor biopsy was performed followed by a single intratumoral injection of 1e10-5e10 virus particles (vp) DNX-2401. Conventional radiotherapy was initiated within 1 month of DNX-2401 administration. Results Enrolled subjects (n=12) had a median age of 9 (range 3–18) and performance scores of 90–100 (n=4; 33%) or 70–80 (n=8; 67%). As part of a dose escalation design, subjects were treated with 1e10 vp (n=4) or 5e10 vp DNX-2401 (n=8), which was then followed by standard RT in 11 of 12 subjects (92%). No dose-limiting toxicities were observed and the treatment regimen was well-tolerated. Adverse events (AEs) have been primarily mild to moderate and consistent with underlying disease. The most commonly reported AEs (≥ 5 subjects), regardless of study drug relationship, include headache, asthenia, vomiting, anemia, leukocytosis, and fever. Two SAEs have been reported including grade 3 lymphopenia and grade 3 abdominal pain. Tumor reductions have been observed and efficacy evaluations are ongoing. As of 09Dec2020, 12-month survival (OS-12) was 71% and 4 of 12 patients had survived > 20 months. Four subjects continue to be followed for survival. Correlative analysis of tumor biopsy and peripheral samples is ongoing. Conclusions DNX-2401 followed by RT can be safely administered to pediatric subjects with newly diagnosed DIPG; clinical activity and preliminary survival are encouraging

Ácaros parásitos de micromamíferos en Cataluña. I. Familia Glycyphagidae

The study of 20 small mammals species -Rodentia. lnsectivora- collected in the Catalonian region, has allowed the discovery of 8 mite species of the family Glycyphagidae: Glycyphagus (Myacarus) hypudaei, Labidophorus talpae. Orycteroxenus dispar, O. soricis. Lophioglyphus liciosus, Sciuropsis eliomys, Xenoryctes punctatus and X. krameri, being S. eliomys a new species for Spain. Host relationships and distribution are discussed.</p

Ácaros parásitos de micromamíferos en Cataluña. II. Familia Listrophoridae

The analysis of 1.395 specimens of small mammals belonging to 20 species has allowed the dis­ covery of 5 acarine species of the family Listrophoridae: Afrolistrophorus apodemi, Listrophorus /euc­ karti, L. meditarreneus, L. meridiana/is and L. occitanus. This study has shown that the Listrophoridae have a strong endemic character and a great capacity to invade other hosts when the habitual of the species is present ·in the same biotop</p

Ácaros parásitos de micromamíferos en Cataluña. III. Familia Myocoptidae

The analysis of 20 small mammals species has allowed the discovery of 9 mite species belonging to the Myocoptidae family: Criniscansor apodemi, Myocoptes j. japonensis, M. musculinus, M. squamosus, Trichoecius apodemi, T. c/ethrionomydis, T. pitymydis, T. romboutsi and T. tenax. This study has shown that the Myocoptidae have a low frequency, a high degree of specificity, and a pronounced focalization in the case of C. apodemi and T. apodemi.</p

Primera denuncia de flebotomos (Diptera, Psychodidae, Phlebotominae) en la provincia de Lérida (España, Cataluña)

The prospection taken in Lerida province (Catalonia, Spain), with the adhesive papers method, has allowed, for the first time in this place, the discovery of flebotomine. In a papers area of 89,2 m2 , 7796 specimens belonging to 5 species were capturad: Phlebotomus papatasi ( 128), P. sergenti (217), P. ariasi (1357), P. perniciosus (1979) and Sergentomyia minuta (4115).</p

Enzymatic heterogeneity among strains of <i>Leishmania infantum</i> from human visceral and cutaneous leishmaniosis in Catalonia

The presence of Sarcocystis spp. was surveyed in 97 sheep in the province of Cordoba. Three methods were used for detection of the parasite in three different muscular location (heart, esophagus and diaphragmatic muscle). Sarcocystis bradyzoites were found in 85,6% of the sheep by trypsin digest. Microscopis S. tenella in all infected animals and S. arieticanis int he diaphragmatic muscle of one sheep, and macroscopic S. gigantea in the esophagus of 6 sheep were identified. The prevalence of the infection varied with the age of the animals