Clinical characteristics and outcomes of hospitalized patients with SARS-CoV-2 infection in a Latin American country: Results from the ECCOVID multicenter prospective study.

BACKGROUND: Clinical features and outcomes of SARS-CoV-2 infections diverge in different countries. The aim of this study was to describe clinical characteristics and outcomes in a cohort of patients hospitalized with SARS-CoV-2 in Argentina. METHODS: Multicenter prospective cohort study of ≥18 years-old patients with confirmed SARS-CoV-2 infection consecutively admitted to 19 hospitals in Argentina. Multivariable logistic regression models were used to identify variables associated with 30-day mortality and admission to intensive care unit (ICU). RESULTS: A total of 809 patients were analyzed. Median age was 53 years, 56% were males and 71% had at least one comorbidity. The most common comorbidities were hypertension (32%), obesity (23%) and diabetes (17%). Disease severity at admission was classified as mild 25%, moderate 51%, severe 17%, and critical 7%. Almost half of patients (49%) required supplemental oxygen, 18% ICU, and 12% invasive ventilation. Overall, 30-day mortality was 11%. Factors independently associated with ICU admission were male gender (OR 1.81; 95%CI 1.16-2.81), hypertension (OR 3.21; 95%CI 2.08-4.95), obesity (OR 2.38; 95%CI 1.51-3.7), oxygen saturation ≤93% (OR 6.45; 95%CI 4.20-9.92) and lymphopenia (OR 3.21; 95%CI 2.08-4.95). Factors independently associated with 30-day mortality included age ≥60 years-old (OR 2.68; 95% CI 1.63-4.43), oxygen saturation ≤93% (OR 3.19; 95%CI 1.97-5.16) and lymphopenia (OR 2.65; 95%CI 1.64-4.27). CONCLUSIONS: This cohort validates crucial clinical data on patients hospitalized with SARS-CoV-2 in Argentina.

Identification of optimal therapeutic window for steroid use in severe alcohol-associated hepatitis: A worldwide study.

BACKGROUND & AIMS: Corticosteroids are the only effective therapy for severe alcohol-associated hepatitis (AH), defined by a model for end-stage liver disease (MELD) score >20. However, there are patients who may be too sick to benefit from therapy. Herein, we aimed to identify the range of MELD scores within which steroids are effective for AH. METHODS: We performed a retrospective, international multicenter cohort study across 4 continents, including 3,380 adults with a clinical and/or histological diagnosis of AH. The main outcome was mortality at 30 days. We used a discrete-time survival analysis model, and MELD cut-offs were established using the transform-the-endpoints method. RESULTS: In our cohort, median age was 49 (40-56) years, 76.5% were male, and 79% had underlying cirrhosis. Median MELD at admission was 24 (19-29). Survival was 88% (87-89) at 30 days, 77% (76-78) at 90 days, and 72% (72-74) at 180 days. A total of 1,225 patients received corticosteroids. In an adjusted-survival-model, corticosteroid use decreased 30-day mortality by 41% (hazard ratio [HR] 0.59; 0.47-0.74; p <0.001). Steroids only improved survival in patients with MELD scores between 21 (HR 0.61; 0.39-0.95; p = 0.027) and 51 (HR 0.72; 0.52-0.99; p = 0.041). The maximum effect of corticosteroid treatment (21-30% survival benefit) was observed with MELD scores between 25 (HR 0.58; 0.42-0.77; p <0.001) and 39 (HR 0.57; 0.41-0.79; p <0.001). No corticosteroid benefit was seen in patients with MELD >51. The type of corticosteroids used (prednisone, prednisolone, or methylprednisolone) was not associated with survival benefit (p = 0.247). CONCLUSION: Corticosteroids improve 30-day survival only among patients with severe AH, especially with MELD scores between 25 and 39. LAY SUMMARY: Alcohol-associated hepatitis is a condition where the liver is severely inflamed as a result of excess alcohol use. It is associated with high mortality and it is not clear whether the most commonly used treatments (corticosteroids) are effective, particularly in patients with very severe liver disease. In this worldwide study, the use of corticosteroids was associated with increased 30-day, but not 90- or 180-day, survival. The maximal benefit was observed in patients with an MELD score (a marker of severity of liver disease; higher scores signify worse disease) between 25-39. However, this benefit was lost in patients with the most severe liver disease (MELD score higher than 51).

Evaluation of classical and novel autoantibodies for the diagnosis of Primary Biliary Cholangitis-Autoimmune Hepatitis Overlap Syndrome (PBC-AIH OS).

BACKGROUND AND AIMS: Up to 20% of Primary Biliary Cholangitis (PBC) patients are estimated to have features that overlap with Autoimmune Hepatitis (AIH). Patients with PBC-AIH overlap syndrome (PBC-AIH OS) have been reported to exhibit suboptimal responses to ursodeoxycholic acid therapy, and are more likely to progress to cirrhosis. Anti-double stranded DNA (anti-dsDNA) and anti-p53 have been previously suggested to be potential autoantibodies for identifying patients with PBC-AIH OS. In our well defined PBC patient cohorts, a comprehensive assessment of various classical and novel autoantibodies was evaluated for their utility in identifying PBC-AIH OS patients. METHODS: PBC-AIH OS was classified according to the Paris criteria and PBC as per the European Association for the Study of the Liver guidelines. Biobanked serum samples from 197 patients at the University of Calgary Liver Unit and the University of Alberta were analyzed for classical and novel autoantibodies. Anti-dsDNA was measured by the Crithidia luciliae immunofluorescence (CLIFT) assay (1:20 dilution) and chemiluminescence (CIA: QUANTA Flash®, Inova Diagnostics, San Diego). Anti-p53, anti-Ro52/TRIM21, anti-YB 1, anti-GW182, anti-Ge-1, and anti-Ago 2 were measured by either an addressable laser bead immunoassay (ALBIA) or line immunoassay (LIA). Autoantibodies against MIT3, gp210, sp100, LKM1, SLA, and the novel autoantibodies Hexokinase-1 (HK-1), and Kelch like protein 12 (KLHL-12) were measured using QUANTA Lite® ELISA assays. We applied non-parametric methods to compare the biomarkers frequencies between study groups. We used multivariate adjusted models and AUROC to compare the diagnostic accuracy of the different autoantibodies alone or in combination with serum biochemistry. RESULTS: 16 out of 197 PBC patients (8.1%) were classified as PBC-AIH OS. Compared to PBC patients, PBC-AIH OS patients were similar in age (median: 59 vs. 63, P = 0.21) and female predominance (94% vs. 89%, P = 1.00). Anti-dsDNA-by CLIFT (37.5% in PBC-AIH OS vs 9.9% in PBC alone, P <0.01) was the only autoantibody associated with PBC-AIH OS; a finding consistent with previous reports. Significant elevation in serum ALT (62 IU/L in PBC-AIH OS vs 37 IU/L in PBC alone, P < 0.01), and serum IgG (17.6 g/L in OS vs 12.1 g/L in PBC alone, P <0.01) were observed in patients with PBC-AIH OS receiving medical/immunosuppressive therapy. In a multivariate model, positive anti-dsDNA by CLIFT, ALT and IgG were significant predictors of PBC-AIH OS with an area under the receiver operator curve (AUROC) value of 0.84. CONCLUSIONS: Consistent with previous findings, the presence of anti-dsDNA by CLIFT is associated with PBC-AIH OS. Contrary to previous reports, anti-p53 was not associated with PBC-AIH OS. Our comprehensive evaluation of various classical and novel autoantibody biomarkers including Ro52/TRIM21, anti-p53, anti-KLHL-12 and anti-HK-1 were not significantly associated with PBC-AIH OS. Our findings highlight the ongoing need for the research and development of new autoantibody biomarkers to aid in the diagnosis of PBC-AIH OS.

Superoxidedismutase-mimetic copper(II) complexes containing saccharinate and 4-aminopyridine/4-cyanopyridine.

Two copper(II) complexes, [Cu(sac)(2)(4-cypy)(2)(H(2)O)], 1 and [Cu(sac)(2)(4-Ampy)(2)(H(2)O)], 2 (4-cypy: 4-cyanopyridine; 4-Ampy: 4-aminopyridine) were prepared. Physicochemical properties of the complexes were studied by spectroscopic (solution UV-vis, diffuse reflectance and IR) techniques. Structural X-ray diffraction data could be obtained only for [Cu(sac)(2)(4-cypy)(2)(H(2)O)] that it crystallized in the tetragonal space group P4cc with a=b=15.313(1), c=13.240(1)A, and Z=4 molecules per unit cell. The complex was cited on a crystallographic C(2)-axis with the Cu(II) ion in a square-pyramidal environment, coordinated at the pyramid basis to the nitrogen atom of two saccharine anions [d(Cu-N)=2.011(3)A] and the pyridine N-atom of two 4-cyanopyridine ligands [d(Cu-N)=2.038(4)A]. The coordination was completed by a water molecule at the pyramid apex [d(Cu-Ow)=2.189(5)A]. Elemental and spectroscopic analyses revealed an O-saccharinate coordination mode for complex 2 and a square-pyramidal structure. Only complex 2 retained its structure in methanolic solution. However, both complexes were able to catalyze the dismutation of superoxide anion (O(2)(-)) (pH 7.5) at micromolar concentrations. Therefore, these complexes behaved as useful SOD-mimetic compounds.

Molecular structure, bioavailability and bioactivity of [Cu(o-phen)2(cnge)](NO3)2.2H2O and [Cu(o-phen)(cnge)(H2O)(NO3)2] complexes.

Two Cu(II) complexes with cyanoguanidine (cnge) and o-phenanthroline, [Cu(o-phen)(2)(cnge)](NO(3))(2).2H(2)O (1) and [Cu(o-phen)(cnge)(H(2)O)(NO(3))(2)] (2), have been synthesized using different experimental techniques and characterized by elemental analyses, FTIR, diffuse and UV-vis spectra and EPR and magnetic moment measurements techniques. The crystal structures of both complexes were solved by X-ray diffraction methods. Complex (1) crystallizes in the monoclinic space group C2/c with a=12.621(5), b=31.968(3), c=15.39(1)A, beta=111.68(4) degrees, and Z=8 and complex (2) in the monoclinic space group P2(1)/n with a=10.245(1), b=13.923(2), c=12.391(2)A, beta=98.07(1) degrees, and Z=4. The environments of the copper(II) center are trigonal bipyramidal (TBP) for [Cu(o-phen)(2)(cnge)](2+) and an elongated octahedron for [Cu(o-phen)(cnge)(H(2)O)(NO(3))(2)]. Solution studies have been performed to determine the species distribution. The superoxide dismutase (SOD) activities of both complexes have also been tested in order to determine if these compounds mimic the enzymatic action of the enzyme SOD that protects cells against peroxide radicals.