Adjunctive use of oral MAF is associated with no disease progression or mortality in hospitalized patients with COVID-19 pneumonia: The single-arm COral-MAF1 prospective trial.

Based on a growing body of evidence that a dysregulated innate immune response mediated by monocytes/macrophages plays a key role in the pathogenesis of COVID-19, a clinical trial was conducted to investigate the therapeutic potential and safety of oral macrophage activating factor (MAF) plus standard of care (SoC) in the treatment of hospitalized patients with COVID-19 pneumonia. Ninety-seven hospitalized patients with confirmed COVID-19 pneumonia were treated with oral MAF and a vitamin D3 supplement, in combination with SoC, in a single-arm, open label, multicentre, phase II clinical trial. The primary outcome measure was a reduction in an intensive care unit transfer rate below 13% after MAF administration. At the end of the study, an additional propensity score matching (PSM) analysis was performed to compare the MAF group with a control group treated with SoC alone. Out of 97 patients treated with MAF, none needed care in the ICU and/or intubation with mechanical ventilation or died during hospitalization. Oxygen therapy was discontinued after a median of nine days of MAF treatment. The median length of viral shedding and hospital stay was 14 days and 18 days, respectively. After PSM, statistically significant differences were found in all of the in-hospital outcomes between the two groups. No mild to serious adverse events were recorded during the study. Notwithstanding the limitations of a single-arm study, which prevented definitive conclusions, a 21-day course of MAF treatment plus SoC was found to be safe and promising in the treatment of hospitalized adult patients with COVID-19 pneumonia. Further research will be needed to confirm these preliminary findings.

Seroprevalence of SARS-CoV-2 Assessed by Four Chemiluminescence Immunoassays and One Immunocromatography Test for SARS-Cov-2.

The onset of the new SARS-CoV-2 coronavirus encouraged the development of new serologic tests that could be additional and complementary to real-time RT-PCR-based assays. In such a context, the study of performances of available tests is urgently needed, as their use has just been initiated for seroprevalence assessment. The aim of this study was to compare four chemiluminescence immunoassays and one immunochromatography test for SARS-Cov-2 antibodies for the evaluation of the degree of diffusion of SARS-CoV-2 infection in Salerno Province (Campania Region, Italy). A total of 3,185 specimens from citizens were tested for anti-SARS-CoV-2 antibodies as part of a screening program. Four automated immunoassays (Abbott and Liaison SARS-CoV-2 CLIA IgG and Roche and Siemens SARS-CoV-2 CLIA IgM/IgG/IgA assays) and one lateral flow immunoassay (LFIA Technogenetics IgG-IgM COVID-19) were used. Seroprevalence in the entire cohort was 2.41, 2.10, 1.82, and 1.85% according to the Liaison IgG, Abbott IgG, Siemens, and Roche total Ig tests, respectively. When we explored the agreement among the rapid tests and the serologic assays, we reported good agreement for Abbott, Siemens, and Roche (Cohen's Kappa coefficient 0.69, 0.67, and 0.67, respectively), whereas we found moderate agreement for Liaison (Cohen's kappa coefficient 0.58). Our study showed that Abbott and Liaison SARS-CoV-2 CLIA IgG, Roche and Siemens SARS-CoV-2 CLIA IgM/IgG/IgA assays, and LFIA Technogenetics IgG-IgM COVID-19 have good agreement in seroprevalence assessment. In addition, our findings indicate that the prevalence of IgG and total Ig antibodies against SARS-CoV-2 at the time of the study was as low as around 3%, likely explaining the amplitude of the current second wave.

The principles of Health Technology Assessment in laboratory medicine.

The Health Technology Assessment (HTA) is a multi-professional and multidisciplinary evaluation approach designed to assess health technology in the broadest sense of the term, from its instruments to the rearranging of its organizational structures. It is by now an established methodology at national and international levels that involves several medical disciplines thanks to its versatility. Laboratory medicine is one of these disciplines. Such specialization was subjected, in recent years, to deep changes even from an organizational standpoint, in order to meet the health needs of the population, making them as effective and cost-effective as possible. In this regard, HTA was the tool used to assess implications in different areas.

Comparison between multiplex PCR and phenotypic systems for Candida spp. identification.

This study evaluated the performances of three phenotypic systems (RapID Yeast panel, Vitek2 YST card, and API 20 C AUX) and multiplex PCR for Candida spp. identification. Four-hundred and fifty clinical strains of Candida spp. were identified with the four systems and results of multiplex PCR were compared with those of phenotypic methods. The best correspondence was obtained between Multiplex PCR and API 20 C AUX (83.7%), but the other comparisons showed similar values (81.7% and 79.3% for Vitek2 and RapID Yeast panel respectively). The correspondence was lower for all the methods in identification of C. krusei; this may be of concern in addition to the azole resistance and the often endogenous origin of this yeast. In the comparison with the three phenotypic methods, multiplex PCR could be reliable and time-saving in the identification of Candida spp. for diagnostics purposes. Nowadays, a large variety of both traditional and molecular methods for Candida spp. identification are commercially available. Multiplex PCR applied in this study may be more rapid and sensitive than phenotypic systems, and less expensive than other molecular methods.

Therapeutic targeting of the stem cell niche in experimental hindlimb ischemia.

BACKGROUND: The custom microenvironment 'vascular niche' is a potential therapeutic target for several pathophysiological conditions. Osteoblasts regulate the hematopoietic stem cell niche, and activation of the parathyroid hormone (PTH) receptor can increase the number of cells mobilized into the bloodstream. METHODS: C57Bl/6 mice were randomly assigned treatment with granulocyte-colony stimulating factor (G-CSF), PTH, G-CSF plus PTH or saline. All mice underwent hindlimb ischemia. Blood flow was measured by laser Doppler imaging. Indices of capillary activity were determined by electron microscopy in muscle tissue. CD34(+) and Ki67(+) cells were detected and evaluated by immunofluorescence, apoptosis by TUNEL, surface antigen and endothelial progenitor cells by fluorescence-activated cell sorting analysis, and vascular endothelial growth factor-164 and angiopoietin-1 expression by reverse-transcriptase polymerase chain reaction. Frozen bone marrow sections were stained for antigen-specific B cells and fibronectin and analyzed by confocal laser scanning microscopy. RESULTS: Following mobilization induced by G-CSF treatment, mice also treated with PTH showed increases in blood flow, capillary density, nitrite/nitrate release, angiogenic factors and circulating progenitor cells, as well as reduced apoptosis, fibrosis, oxidative stress and inflammation in ischemic muscles. Furthermore, hematopoietic antigen-specific B cells in the bone marrow were also increased by G-CSF alone and in combination with PTH. CONCLUSIONS: PTH might increase the efficiency of hematopoietic stem-cell-based therapy in a recognized model of peripheral ischemia. Our translational experimental therapeutic targeting of the vascular niche points to novel clinical targets for the hematopoietic stem-cell treatment of ischemic vascular diseases.

Functional impairment of hematopoietic progenitor cells in patients with coronary heart disease.

The circulating form of endothelial progenitors cells (EPCs) are derived from bone marrow (BM)-derived hematopoietic stem cells (HSCs). Enhanced mobilization of EPCs was shown to be linked to cardiac diseases. This study investigated whether reduced EPC levels in advanced coronary heart disease (CHD) are secondary to a functional exhaustion of HSCs in the BM or to reduced mobilization. Number and functional properties of EPCs were assessed in 15 healthy controls, and 40 patients with CHD. The colony-forming unit (CFU) capacity of BM-derived mononuclear cells and the CD34+ HSC number were examined in four healthy volunteers, and 15 CHD patients. EPC number was reduced in CHD patients (P < 0.01 vs. controls). Moreover, the migratory capacity was significantly impaired in EPCs of CHD patients (P < 0.05 vs. controls). On multivariate analysis, CHD was an independent predictor of functional EPC impairment. CFUs were reduced in CHD patients (59.6 +/- 21.2 vs. 75.4 +/- 25.8 in controls, P < 0.05). CHD was also predictor of impaired CFU capacity. In this small clinical study, CHD is associated with selective impairment of HSC function in the BM and in the peripheral blood, which may contribute to impairment of cardiac function.

Maximal suppression of renin-angiotensin system in nonproliferative glomerulonephritis.

BACKGROUND: Elimination of residual proteinuria is the novel target in renoprotection; nevertheless, whether a greater suppression of renin-angiotensin system (RAS) effectively improves the antiproteinuric response in patients with moderate proteinuria remains ill-defined. METHODS: We evaluated the effects of maximizing RAS suppression on quantitative and qualitative proteinuria in ten patients with stable nonnephrotic proteinuria (2.55 +/- 0.94 g/24 hours) due to primary nonproliferative glomerulonephritis (NPGN), and normal values of creatinine clearance (103 +/- 17 mL/min). The study was divided in three consecutive phases: (1) four subsequent 1-month periods of ramipril at the dose of 2.5, 5.0, 10, and 20 mg/day; (2) 2 months of ramipril 20 mg/day + irbesartan 300 mg/day; and (3) 2 months of irbesartan 300 mg/day alone. RESULTS: Maximizing RAS suppression was not coupled with any major effect on renal function and blood pressure; conversely, a significant decrement in hemoglobin levels, of 0.8 g/dL on average, was observed during up-titration of ramipril dose. The 2.5 mg dose of ramipril significantly decreased proteinuria by 29%. Similar changes were detected after irbesartan alone (-28%). The antiproteinuric effect was not improved either by the higher ramipril doses (-30% after the 20 mg dose) or after combined treatment (-33%). The reduction of proteinuria led to amelioration of the markers of tubular damage, as testified by the significant decrement of alpha 1 microglobulin (alpha 1m) excretion and of the tubular component of proteinuria at sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). CONCLUSION: In nonnephrotic NPGN patients, standard doses of either ramipril or irbesartan lead to significant reduction of residual proteinuria and amelioration of the qualitative features suggestive of tubular damage. The enhancement of RAS suppression up to the maximal degree does not improve the antiproteinuric response and is coupled with a decrement of hemoglobin levels.