Expansion of plasmablasts and loss of memory B cells in peripheral blood from COVID-19 patients with pneumonia

Studies on the interactions between SARS-CoV-2 and humoral immunity are fundamental to elaborate effective therapies including vaccines. We used polychromatic flow cytometry, coupled with unsupervised data analysis and principal component analysis (PCA), to interrogate B cells in untreated patients with COVID-19 pneumonia. COVID-19 patients displayed normal plasma levels of the main immunoglobulin classes, of antibodies against common antigens or against antigens present in common vaccines. However, we found a decreased number of total and naïve B cells, along with decreased percentages and numbers of memory switched and unswitched B cells. On the contrary, IgM⁺ and IgM⁻ plasmablasts were significantly increased. In vitro cell activation revealed that B lymphocytes showed a normal proliferation index and number of dividing cells per cycle. PCA indicated that B-cell number, naive and memory B cells but not plasmablasts clustered with patients who were discharged, while plasma IgM level, C-reactive protein, D-dimer, and SOFA score with those who died. In patients with pneumonia, the derangement of the B-cell compartment could be one of the causes of the immunological failure to control SARS-Cov2, have a relevant influence on several pathways, organs and systems, and must be considered to develop vaccine strategies.     

ABCB4 and ABCB11 mutations in intrahepatic cholestasis of pregnancy in an Italian population

BackgroundGenetic alterations in the ATP-binding cassette subfamily B member 4 (ABCB4) and ATP-binding cassette subfamily B member 11 (ABCB11) have been associated to the onset of intrahepatic cholestasis of pregnancy (ICP) in predisposed women.AimsTo identify new and/or frequent ABCB4 and ABCB11 genes variants in a cohort of Italian patients with ICP and to evaluate the possible pathogenetic role for the novel mutations identified.MethodsDNA of 33 unrelated Italian women with obstetric cholestasis were screened for mutations in the entire coding sequence of ABCB4 and ABCB11 genes. Polymerase chain reaction and automated sequencing was performed on the 27 coding exons of both genes.ResultsGenotyping revealed 11 mutations, 5 of whom were novel variants: 2 localized on ABCB4 (p.I587DfsX603, p.I738LfsX744) and 3 on ABCB11 (p.V284D, p.Q558H, p.P731S). The most severe phenotypes were associated with the variants p.I587DfsX603, p.I738LfsX744 and p.V284D. Moreover, the already described mutation p.N510S found in ABCB4 seems to be strictly involved in the onset of ICP in that particular patient.ConclusionsOur data support the hypothesis of a significant involvement of ABCB4 mutations in the onset of ICP, but also confirm an important role for ABCB11 mutations in increasing the susceptibility to cholestasis of pregnancy.     

Incidence,risk factors and outcome of acute kidney injury (AKI) in patients with COVID-19

Clinical and Experimental Nephrology - Acute kidney injury (AKI) is a severe complication of coronavirus disease-2019 (COVID-19). This study aims to evaluate incidence, risk factors and...     

Comparison of two perioperative antibiotic schedules in patients undergoing surgical reconstruction with dermal matrix after excision of skin cancer

Perioperative antibiotic treatment duration in skin reconstruction with dermal substitutes is not well established. This study compares the incidence of infective complications after two different durations of perioperative antibiotic treatment in patients undergoing surgical reconstruction with skin dermal substitutes (SDS) after excision of skin cancer. Infective complications at the site of SDS were compared in subjects undergoing surgical reconstruction who received either a > 24‐hour (extended protocol) or a ≤ 24‐hour (short protocol) perioperative antibiotic treatment. Of 116 patients undergoing SDS surgical reconstruction, 62 (53.4%) received an extended schedule, and 54 (46.6%) received a short schedule. The two groups were similar for gender, age, comorbidities, American Society of Anesthesiologists score, and type of skin cancer. Overall incidence rate of infection was 20.7% (24/116). No differences in terms of risk of infection were observed between the two groups (OR: 1.04, 95% CI: 0.42‐2.55; P = .937). Patients undergoing SDS reconstruction in the limb/foot had a higher risk of infection in comparison with those undergoing SDS reconstruction in the chest/head (OR: 2.69, 95% CI: 1.06‐6.86; P = .038). The short protocol was demonstrated to be beneficial to patients undergoing surgical reconstruction with SDS. A ≤ 24‐hour perioperative antibiotic schedule did not increase the infection rate, potentially allowing a reduction of antibiotic exposure.     

Reduction trend of mcr-1 circulation in Emilia-Romagna Region,Italy

European Journal of Clinical Microbiology & Infectious Diseases - This study aims to describe trends of mcr-positive Enterobacterales in humans based on laboratory surveillance with a defined...     

Captopril and Lisinopril Only Inhibit Matrix Metalloproteinase‐2 (MMP‐2) Activity at Millimolar Concentrations

Matrix metalloproteinase‐2 (MMP‐2) shares structural similarities with the angiotensin‐converting enzyme (ACE). ACE inhibitors have been described to inhibit MMP‐2, but this inhibitory potential was not shown using a highly purified MMP‐2. This study aimed to investigate the inhibitory potential of captopril and lisinopril regarding MMP‐2 activity. The first objective was to test the potential of captopril to change the pH of the buffer solution. The second objective was to test the direct inhibitory effect of captopril and lisinopril on plasma MMP‐2 and on recombinant human MMP‐2 (rhMMP‐2). The in vitro activity assays included gelatin zymography and a fluorimetric assay. Captopril solubilization significantly decreased the pH of the 50 mM Tris buffer solution at the following concentrations: 2 mM (p < 0.05), 4  mM and 8 mM (p < 0.01), while only the 8 mM lisinopril induced a drop in pH (p < 0.05). Thus, only 200 mM buffer solutions were used. Zymography results of plasma MMP‐2 and rhMMP‐2 showed that inhibition only happened at captopril concentrations ≥ 4 and 1 mM, respectively (p < 0.05), while only the higher concentration of lisinopril (8 mM) inhibited plasma MMP‐2 (p < 0.05). In the fluorimetric assay, captopril led to significant inhibition of the rhMMP‐2 activity at concentrations ≥2 mM (p < 0.01), whereas aminophenylmercuric acetate‐activated rhMMP‐2 was inhibited by 0.5 mM captopril (p < 0.01). The captopril and lisinopril concentrations found to inhibit MMP‐2 are 3 orders of magnitude higher than those present in vivo after drug administration. We also discuss possible pitfalls for gelatinase inhibitory assays (besides the obvious pH problem already cited). In conclusion, this study's data show that captopril and lisinopril did not inhibit MMP‐2 directly at the concentrations reached in vivo.