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ROLE OF BLOOD PRESSURE DYSREGULATION ON KIDNEY AND MORTALITY OUTCOMES IN COVID-19
Background: Since February 2020 COVID-19 infection spread in Italy, violently hitting the Lombardy region. Despite high diffusion, only a subset of patients developed severe COVID-19: around 25% of them developed AKI and one-third of them died. Elderly patients and patients with high comorbidity have been identified as at higher risk of severe COVID-19.
Methods: In a prospective observational cohort study 392 consecutive patients hospitalized for COVID-19 in Milan (age 67 years, 75% male) were included. We evaluated the relationship between blood pressure at presentation, presence of AKI at Emergency Room presentation and during hospitalization, and total in-hospital mortality (24%).
Results: Despite 58% reported a history of hypertension (86% treated) 30% of patients presented with low blood pressure levels. Only 5.5% were diagnosed with AKI on admission; 75% of hypertensive patients discontinued therapy during hospitalization (only 20% were treated at discharge).
Gender and hypertension were strongly associated with AKI at admission time (odds ratio 11). Blood pressure was inversely correlated with increased risk of AKI upon admission, independently of the severity of respiratory distress. Age over 65, history of hypertension, and severity of respiratory distress were the main predictors of AKI during hospitalization (developed in 34.7% of the cases).
AKI was associated with increased in-hospital mortality. Hypertension and low levels of blood pressure at presentation were the main predictors of in-hospital mortality, together with age over 65, baseline pulmonary involvement, and severity of illness.
Conclusions: In patients hospitalized for COVID-19, hypertension and low levels of blood pressure at presentation are important risk factors for AKI and mortality. Early reduction of antihypertensive therapy may improve outcomes in SARS-CoV-2 infection.
doi: 10.17632/2kj8jfgndw.
data from Clinical associations and prognostic implications of repair tissue proliferation in eyes with retinal pigment epithelium tears
the data comes from Cicinelli MV, Rabiolo A, Montesano G, Marchese A, Barresi C, Introini U, Parodi MB, Bandello F. Clinical associations and prognostic implications of repair tissue proliferation in eyes with retinal pigment epithelium tears. Retina. 2021 Nov 2. doi: 10.1097/IAE.0000000000003332. Epub ahead of print. PMID: 34743132
A functional interaction between liprin-alpha1 and B56gamma regulatory subunit of protein phosphatase 2A supports tumor cell motility
PLEASE REFER TO THE PUBLICATION:
Journal: Communications Biology.
DOI : 10.1038/s42003-022-03989-3
Title : A functional interaction between liprin-α1 and B56γ regulatory subunit of protein phosphatase 2A supports tumor cell motility.
Scaffold liprin-alpha1 is required to assemble dynamic plasma membrane-associated platforms (PMAPs) at the front of migrating breast cancer cells, to promote protrusion and invasion. We show that the N-terminal region of liprin-alpha1 contains an LxxIxE motif interacting with B56 regulatory subunits of serine/threonine protein phosphatase 2A (PP2A). The specific interaction of B56gamma with liprin-alpha1 requires an intact motif, since two point mutations strongly reduce the interaction. B56gamma mediates the interaction of liprin-alpha1 with the heterotrimeric PP2A holoenzyme. Most B56gamma protein is recovered in the cytosolic fraction of invasive MDA-MB-231 breast cancer cells, where B56gamma is complexed with liprin-alpha1. While mutation of the short linear motif (SLiM) does not affect localization of liprin-alpha1 to PMAPs, localization of B56gamma at these sites specifically requires liprin-alpha1. Silencing of B56gamma or liprin-alpha1 inhibits to similar extent cell spreading on extracellular matrix, invasion, motility and lamellipodia dynamics in migrating MDA-MB-231 cells, suggesting that B56gamma-PP2A is a novel component of the PMAPs machinery regulating tumor cell motility. In this direction, inhibition of cell spreading by silencing liprin-alpha1 is not rescued by expression of B56gamma binding-defective liprin-alpha1 mutant. We propose that liprin-alpha1-mediated recruitment of PP2A via B56gamma regulates cell motility by controlling protrusion in migrating MDA-MB-231 cells
A/H1N1 hemagglutinin antibodies show comparable affinity in vaccine-related Narcolepsy type 1 and control and are unlikely to contribute to pathogenesis
data used in figures and tables from paper Sci Rep . 2021 Feb 18;11(1):4063. doi: 10.1038/s41598-021-83543-z.
A/H1N1 hemagglutinin antibodies show comparable affinity in vaccine-related Narcolepsy type 1 and control and are unlikely to contribute to pathogenesis
Alexander Lind # 1 , Ilaria Marzinotto # 2 , Cristina Brigatti 2 , Anita Ramelius 1 , Lorenzo Piemonti 2 , Vito Lampasona 3
Affiliations 1 Department of Clinical Sciences, Clinical Research Center (CRC), Skåne University Hospital SUS, Lund University, Malmö, Sweden. 2 San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy. 3 San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy. [email protected]. # Contributed equally.
PMID: 33603024 PMCID: PMC7893011 DOI: 10.1038/s41598-021-83543-
Use of edge-to-edge percutaneous mitral valve repair for severe mitral regurgitation in cardiogenic shock: A multicenter observational experience (MITRA-SHOCK study)
DOI: 10.1002/ccd.29683
Patients with cardiogenic shock and concomitant severe mitral regurgitation have high mortality rates. This study evaluated the procedural safety and efficacy at short and mid-term of edge-to-edge percutaneous mitral valve repair (PMVR) in this setting. We found that edge-to-edge PMVR had an acceptable complication rate and procedural success was a predictor of both 30-day and 6-month survival. We concluded that edge-to-edge PMVR is a safe and effective procedure in patients with severe mitral regurgitation complicating cardiogenic shock and could be considered a bailout option in this setting
data fromPersistent or Recurrent Diabetic Macular Edema After Fluocinolone Acetonide 0.19 mg Implant: Risk Factors and Management.
data fromPersistent or Recurrent Diabetic Macular Edema After Fluocinolone Acetonide 0.19 mg Implant: Risk Factors and Management.
DOI: 10.1016/j.ajo.2020.03.01
Different decay of antibody response and VOC sensitivity in naïve and previously infected subjects at 15 weeks following vaccination with BNT162b2
The associate DOI for this manuscript is: https://doi.org/10.1186/s12967-021-03208-3
Published in 2022 by Lucia Lopalco et al.
Twenty-six naïve and 9 previously SARS-CoV-2 infected subjects during the second wave of the pandemic
in Italy were enrolled for this study. The two groups had comparable demographic and clinical characteristics. By
means of ELISA and pseudotyped-neutralization assays, we investigated the kinetics of developed IgG-RBD and their
neutralizing activity against both the ancestral D614G and the SARS-CoV-2 variants of concern emerged later, respectively.
Although after 15 weeks from vaccination IgG-RBD dropped in all participants, naïve subjects experienced
a more dramatic decline than those with previous SARS-CoV-2 infection. Neutralizing antibodies remained higher in
subjects with SARS-CoV-2 history and conferred broad-spectrum protection.
A table including all clinical data, ELISA and Neutralization assay is attached here (named Vaccinated + Neut + ELISA
Self-expanding transcatheter aortic valve infolding: Current evidence, diagnosis, and management.
Background: Prosthetic valve infolding is a rare but severe complication of transcatheter aortic valve implantation (TAVI) with self-expanding valves. However, currently available clinical data are limited and fragmented.
Objectives: This report aims to provide a comprehensive overview of this complication focusing on predisposing factors, clinical presentation, diagnostic findings, treatment and clinical outcomes.
Methods: A systematic review of the literature was performed to identify cases of infolding occurring during TAVI with self-expanding valves published until August 2020. These data were pooled with all the retrospectively identified infolding cases occurred at San Raffaele Scientific Institute between December 2014 and August 2020.
Results: A total of 34 cases were included. Among patients with available data, 38% received a first-generation CoreValve, and 62% a second-generation Evolut R (82%) or Evolut PRO (18%). Infolding occurred mostly with ≥29-mm valves (94%). Predisposing factors included resheathing of a second-generation valve (82%), heavy calcification of the native valve (65%), lack of predilatation (16%), Sievers type-1 bicuspid aortic valve (11%), and improper valve loading (5%). Infolding resulted in severe PVL causing hemodynamic instability (29%) or cardiac arrest (12%).
Postdilatation was the treatment strategy in 68%, while prosthesis replacement with a new device in 23% of cases. Device success rate was 82%. Death and stroke occurred in 3% and 12% of cases.
Conclusions: Prosthetic valve infolding is typically observed after resheathing of a large-size self-expanding TAVI. When infolding is timely diagnosed, prosthesis removal and replacement should be pursued. Further studies are required to precisely define predisposing factors to prevent this complication.
doi: 10.1002/ccd.29432
10.1021/acs.jmedchem.1c00533: Halting the Spread of Herpes Simplex Virus-1: The Discovery of an Effective Dual αvβ6/αvβ8 Integrin Ligand
1. Data_supplementary_tableS2.csv contains the 1H Amide chemical shifts of the molecule 6 as function of temperature. These values have been used to calculate the corresponding temperature factors reported in Supplementary Table S3 in
10.1021/acs.jmedchem.1c00533
2. Data_supplementary_tableS3.csv thsi table continas the data (NOE intensities) of molecule 6 used to generate the distance restraints displayd in Supplementary table S3 in 10.1021/acs.jmedchem.1c0053
In vivo magnetic resonance spectroscopy in the brain of Cdkl5 null mice reveals a metabolic profile indicative of mitochondrial dysfunctions
Mutations in the X-linked CDKL5 gene cause CDKL5 deficiency disorder (CDD), a severe neurodevelopmental condition mainly characterized by infantile epileptic encephalopathy, intellectual disability, and autistic features. The molecular mechanisms underlying the clinical symptoms remain largely unknown and the identification of reliable biomarkers in animal models will certainly contribute to increase our comprehension of CDD as well as to assess the efficacy of therapeutic strategies. Here, we used different Magnetic Resonance (MR) methods to disclose structural, functional, or metabolic signatures of Cdkl5 deficiency in the brain of adult mice. We found that loss of Cdkl5 does not cause cerebral atrophy but affects distinct brain areas, particularly the hippocampus. By in vivo proton-MR spectroscopy (MRS), we revealed in the Cdkl5 null brain a metabolic dysregulation indicative of mitochondrial dysfunctions. Accordingly, we unveiled a significant reduction in ATP levels and a decrease in the expression of complex IV of mitochondrial electron transport chain. Conversely, the number of mitochondria appeared preserved. Importantly, we reported a significant defect in the activation of one of the major regulators of cellular energy balance, the adenosine monophosphate-activated protein kinase (AMPK), that might contribute to the observed metabolic impairment and become an interesting therapeutic target for future preclinical trials. In conclusion, MRS revealed in the Cdkl5 null brain the presence of a metabolic dysregulation suggestive of a mitochondrial dysfunction that permitted to foster our comprehension of Cdkl5 deficiency and brought our interest towards targeting mitochondria as therapeutic strategy for CDD.
DOI: 10.1111/jnc.1530