Time course of risk factors associated with mortality of 1260 critically ill patients with COVID-19 admitted to 24 Italian intensive care units

Purpose: To evaluate the daily values and trends over time of relevant clinical, ventilatory and laboratory parameters during the intensive care unit (ICU) stay and their association with outcome in critically ill patients with coronavirus disease 19 (COVID-19). Methods: In this retrospective–prospective multicentric study, we enrolled COVID-19 patients admitted to Italian ICUs from February 22 to May 31, 2020. Clinical data were daily recorded. The time course of 18 clinical parameters was evaluated by a polynomial maximum likelihood multilevel linear regression model, while a full joint modeling was fit to study the association with ICU outcome. Results: 1260 consecutive critically ill patients with COVID-19 admitted in 24 ICUs were enrolled. 78% were male with a median age of 63 [55–69] years. At ICU admission, the median ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) was 122 [89–175] mmHg. 79% of patients underwent invasive mechanical ventilation. The overall mortality was 34%. Both the daily values and trends of respiratory system compliance, PaO2/FiO2, driving pressure, arterial carbon dioxide partial pressure, creatinine, C-reactive protein, ferritin, neutrophil, neutrophil–lymphocyte ratio, and platelets were associated with survival, while for lactate, pH, bilirubin, lymphocyte, and urea only the daily values were associated with survival. The trends of PaO2/FiO2, respiratory system compliance, driving pressure, creatinine, ferritin, and C-reactive protein showed a higher association with survival compared to the daily values. Conclusion: Daily values or trends over time of parameters associated with acute organ dysfunction, acid–base derangement, coagulation impairment, or systemic inflammation were associated with patient survival

4-Fluoroproline derivative peptides: effect on PPII conformation and SH3 affinity.

Eukaryotic signal transduction involves the assembly of transient protein-protein complexes mediated by modular interaction domains. Specific Pro-rich sequences with the consensus core motif PxxP adopt the PPII helix conformation upon binding to SH3 domains. For short Pro-rich peptides, little or no ordered secondary structure is usually observed before binding interactions. The association of a Pro-rich peptide with the SH3 domain involves unfavorable binding entropy due to the loss of rotational freedom on forming the PPII helix. With the aim of stabilizing the PPII helix conformation in the Pro-rich HPK1 decapeptide PPPLPPKPKF (P2), a series of P2 analogues was prepared, in which specific Pro positions were alternatively occupied by 4(S)- or 4(R)-4-fluoro-L-proline. The interactions of these peptides with the SH3 domain of the HPK1-binding partner HS1 were quantitatively analyzed by the NILIA-CD approach. A CD thermal analysis of the P2 analogues was performed to assess their propensity to adopt the PPII helix conformation. Contrary to our expectations, the Kd values of the analogues were lower than that of the parent peptide P2. These results clearly show that the induction of a stable PPII helix conformation in short Pro-rich peptides is not sufficient to increase their affinity toward the SH3 domain and that the effect of 4-fluoroproline strongly depends on the position of this residue in the sequence and the chirality of the substituent in the pyrrolidine ring. Copyright \ua9 2006 European Peptide Society and John Wiley & Sons, Ltd

Coumarin as attractive casein kinase 2(CK2) inhibitor scaffold: an integrated approach to elucidate the putative binding motif and explain structure-activity relationship.

Casein kinase 2 (CK2) is an ubiquitous, essential, and highly pleiotropic protein kinase whose abnormally high constitutive activity is suspected to underlie its pathogenic potential in neoplasia and other diseases. Recently, using different virtual screening approaches, we have identified several novel CK2 inhibitors. In particular, we have discovered that coumarin moiety can be considered an attractive CK2 inhibitor scaffold. In the present work, we have synthetized and tested a small library of coumarins (more than 60), rationalizing the observed structure-activity relationship. Moreover, the most promising inhibitor, 3,8-dibromo-7-hydroxy-4-methylchromen-2-one (DBC), has been also crystallized in complex with CK2, and the experimental binding mode has been used to derive a linear interaction energy (LIE) model

Use of ultrasound by registered nurses—a systematic literature review

© 2017 European Dialysis and Transplant Nurses Association/European Renal Care Association Background: In Western Australia (WA), most stable patients undergoing haemodialysis receive treatment in a satellite setting where no doctors are on-site during treatment hours, so nurses must make critical decisions about fluid removal. Some patients regularly experience adverse events during dialysis (intradialytic), often due to excessive ultrafiltration goals, with intradialytic hypotension being particularly challenging. Ultrasound of the inferior vena cava has been previously demonstrated being a rapid and non-invasive method for volume assessment on haemodialysis patients, thus could hold valuable information for the treating nurse. Aim: This paper examines the existing literature in regards to the use of ultrasound measurements of the inferior vena cava in patients on haemodialysis for objective assessment of their intravascular volume status by renal nurses. Method: A systematic literature review was performed within medical and nursing databases including CINAHL Plus with Full Text, SCOPUS, Web of Science and MEDLINE. Results: Renal nurses are conscious of the significance of intradialytic hypotension and have only limited options for its prevention. Ultrasound of the inferior vena cava could add another objective dimension for intravascular volume assessment and prevention of intradialytic hypotension, but to date renal nurses have not been using this technique. Conclusions: Ultrasound of the inferior vena cava has the potential to assist in defining the ultrafiltration goal for that particular dialysis session, thus reducing the risk of intradialytic hypotension. Additionally, it has potential to change current renal nursing practice when added to clinical nursing assessment methods. Further studies are required to validate this assessment tool carried out by a renal nurse compared with a skilled ultrasonographer