Complete Loss of EPCAM Immunoexpression Identifies EPCAM Deletion Carriers in MSH2-Negative Colorectal Neoplasia

The use of epithelial cell adhesion molecule (EPCAM) immunohistochemistry (IHC) is not included in the colorectal cancer (CRC) screening algorithm to detect Lynch syndrome (LS) patients. The aim of the present study was to demonstrate that EPCAM IHC is a useful tool to guide the LS germ-line analysis when a loss of MSH2 expression was present. We retrospectively studied MSH2 and EPCAM IHC in a large series of 190 lesions composed of malignant neoplasms (102), precursor lesions of gastrointestinal (71) and extra-gastrointestinal origin (9), and benign neoplasms (8) from different organs of 71 patients suspicious of being LS due to MSH2 alterations. LS was confirmed in 68 patients, 53 with MSH2 mutations and 15 with EPCAM 3'-end deletions. Tissue microarrays were constructed with human normal tissues and their malignant counterparts to assist in the evaluation of EPCAM staining. Among 154 MSH2-negative lesions, 17 were EPCAM-negative, including 10 CRC and 7 colorectal polyps, and 5 of them showed only isolated negative glands. All lesions showing a lack of EPCAM expression belonged to patients with EPCAM 3'-end deletions. EPCAM IHC is a useful screening tool, with 100% specificity to identify LS patients due to EPCAM 3'-end deletions in MSH2-negative CRC and MSH2-negative colorectal polyps

The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with non-severe COVID-19: A pilot, double-blind, placebo-controlled, randomized clinical trial.

Background Ivermectin inhibits the replication of SARS-CoV-2 in vitro at concentrations not readily achievable with currently approved doses. There is limited evidence to support its clinical use in COVID-19 patients. We conducted a Pilot, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of a single dose of ivermectin reduce the transmission of SARS-CoV-2 when administered early after disease onset. Methods Consecutive patients with non-severe COVID-19 and no risk factors for complicated disease attending the emergency room of the Clínica Universidad de Navarra between July 31, 2020 and September 11, 2020 were enrolled. All enrollments occurred within 72 h of onset of fever or cough. Patients were randomized 1:1 to receive ivermectin, 400 mcg/kg, single dose (n = 12) or placebo (n = 12). The primary outcome measure was the proportion of patients with detectable SARS-CoV-2 RNA by PCR from nasopharyngeal swab at day 7 post-treatment. The primary outcome was supported by determination of the viral load and infectivity of each sample. The differences between ivermectin and placebo were calculated using Fisher's exact test and presented as a relative risk ratio. This study is registered at ClinicalTrials.gov: NCT04390022. Findings All patients recruited completed the trial (median age, 26 [IQR 19-36 in the ivermectin and 21-44 in the controls] years; 12 [50%] women; 100% had symptoms at recruitment, 70% reported headache, 62% reported fever, 50% reported general malaise and 25% reported cough). At day 7, there was no difference in the proportion of PCR positive patients (RR 0·92, 95% CI: 0·77-1·09, p = 1·0). The ivermectin group had non-statistically significant lower viral loads at day 4 (p = 0·24 for gene E; p = 0·18 for gene N) and day 7 (p = 0·16 for gene E; p = 0·18 for gene N) post treatment as well as lower IgG titers at day 21 post treatment (p = 0·24). Patients in the ivermectin group recovered earlier from hyposmia/anosmia (76 vs 158 patient-days; p < 0.001). Interpretation Among patients with non-severe COVID-19 and no risk factors for severe disease receiving a single 400 mcg/kg dose of ivermectin within 72 h of fever or cough onset there was no difference in the proportion of PCR positives. There was however a marked reduction of self-reported anosmia/hyposmia, a reduction of cough and a tendency to lower viral loads and lower IgG titers which warrants assessment in larger trials. Funding ISGlobal, Barcelona Institute for Global Health and Clínica Universidad de Navarra

Potential relation of cardiovascular risk factors to disease activity in patients with axial spondyloarthritis

Background: Axial spondyloarthritis (axSpA) patients are known to have a higher prevalence of several comorbidities, including, among others, an increased risk of atherosclerosis, hypertension, dyslipidemia, and diabetes. The purpose of the present study was to determine whether the sum of traditional cardiovascular (CV) risk factors is related to disease characteristics, such as disease activity, in patients with axSpA. Methods: A cross-sectional study that encompassed 804 patients with axSpA was conducted. Patients were assessed for the presence of five traditional CV risk factors (diabetes mellitus, dyslipidemia, hypertension, obesity, and smoking status), and disease activity measurements. A multivariable regression analysis was performed to evaluate whether the number of classic CV risk factors was independently associated with specific features of the disease, to include disease activity. Results: A multivariable analysis showed that Ankylosing Spondylitis Disease Activity Score-C reactive protein (ASDAS-CRP) activity score was significantly higher in patients with 1 [beta coefficient 0.3 (95% confidence interval (CI) 0.1-0.5), p = 0.001] and ?2 [beta coefficient 0.5 (95% CI 0.3-0.7), p = 0.000] CV risk factors compared with those without CV risk factors. Similarly, patients with 1 [OR 2.00 (95%CI 0.99-4.02), p = 0.053] and ?2 [OR 3.39 (95%CI 1.82-6.31), p = 0.000] CV risk factors had a higher odds ratio for the presence of high disease activity compared with the zero CV category. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) activity score was significantly associated with the number of CV risk factors, being higher in patients with more CV risk factors. These relationships showed a CV risk factor-dependent effect being beta coefficients and ORs higher for the effect of ?2 over 1 CV risk factor. Conclusion: Among patients with axSpA, as the number of traditional CV risk factors increased, disease activity similarly increases in an independent manner.Funding: The authors disclosed receipt of the following financial support for the research, authorship, and/ or publication of this article: This research was funded by a grant to MAG-G from the Instituto de Salud Carlos III (ISCIII) (Fondo de Investigación Sanitaria grants PI06/0024, PI09/00748, PI12/00060, PI15/00525, PI18/00043) and the ISCIII RETICS programs (RD12/0009 and RD16/0012)

CCDC 999506: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures

CCDC 999505: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures

CCDC 999508: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures

CCDC 999509: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures

CCDC 999507: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures

Linking Cr3 triangles through phosphonates and lanthanides: Synthetic, structural, magnetic and EPR studies

Reaction of oxo-centered Cr(iii) triangles with a lanthanide salt and t-butylphosphonate leads to {Cr6Ln2} compounds. Magnetic and EPR studies show the ground state of the individual Cr triangles is S = 3/2 with little communication between them.</p