A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Comprehensive analysis of the major histocompatibility complex in systemic sclerosis identifies differential HLA associations by clinical and serological subtypes

Objective: The greatest genetic effect reported for systemic sclerosis (SSc) lies in the major histocompatibility complex (MHC) locus. Leveraging the largest SSc genome-wide association study, we aimed to fine-map this region to identify novel human leucocyte antigen (HLA) genetic variants associated with SSc susceptibility and its main clinical and serological subtypes. Methods: 9095 patients with SSc and 17 584 controls genome-wide genotyped were used to impute and test single-nucleotide polymorphisms (SNPs) across the MHC, classical HLA alleles and their composite amino acid residues. Additionally, patients were stratified according to their clinical and serological status, namely, limited cutaneous systemic sclerosis (lcSSc), diffuse cutaneous systemic sclerosis (dcSSc), anticentromere (ACA), antitopoisomerase (ATA) and anti-RNApolIII autoantibodies (ARA). Results: Sequential conditional analyses showed nine SNPs, nine classical alleles and seven amino acids that modelled the observed associations with SSc. This confirmed previously reported associations with HLA-DRB1∗11:04 and HLA-DPB1∗13:01, and revealed a novel association of HLA-B∗08:01. Stratified analyses showed specific associations of HLA-DQA1∗02:01 with lcSSc, and an exclusive association of HLA-DQA1∗05:01 with dcSSc. Similarly, private associations were detected in HLA-DRB1∗08:01 and confirmed the previously reported association of HLA-DRB1∗07:01 with ACA-positive patients, as opposed to the HLA-DPA1∗02:01 and HLA-DQB1∗03:01 alleles associated with ATA presentation. Conclusions: This study confirms the contribution of HLA class II and reveals a novel association of HLA class I with SSc, suggesting novel pathways of disease pathogenesis. Furthermore, we describe specific HLA associations with SSc clinical and serological subtypes that could serve as biomarkers of disease severity and progression

Is Mn-Bound Substrate Water Protonated in the S2 State of Photosystem II?

In spite of great progress in resolving the geometric structure of the water-splitting Mn4OxCa cluster in photosystem II, the binding sites and modes of the two substrate water molecules are still insufficiently characterized. While time-resolved membrane-inlet mass spectrometry measurements indicate that both substrate water molecules are bound to the oxygen-evolving complex (OEC) in the S2 and S3 states (Hendry and Wydrzynski in Biochemistry 41:13328–13334, 2002), it is not known (1) if they are both Mn-bound, (2) if they are terminal or bridging ligands, and (3) in what protonation state they are bound in the different oxidation states Si (i = 0, 1, 2, 3, 4) of the OEC. By employing 17O hyperfine sublevel correlation (HYSCORE) spectroscopy we recently demonstrated that in the S2 state there is only one (type of) Mn-bound oxygen that is water exchangeable. We therefore tentatively identified this oxygen as one substrate ‘water’ molecule, and on the basis of the finding that it has a hyperfine interaction of about 10 MHz with the electron spin of the Mn4OxCa cluster, we suggest that it is bound as a Mn–O–Mn bridge within a bis-μ2 oxo-bridged unit (Su et al. in J Am Chem Soc 130:786–787, 2008). Employing pulse electron paramagnetic resonance, 1H/2H Mims electron-nuclear double resonance and 2H-HYSCORE spectroscopies together with 1H/2H-exchange here, we test this hypothesis by probing the protonation state of this exchangeable oxygen. We conclude that this oxygen is fully deprotonated. This result is discussed in the light of earlier reports in the literature

Transfusion-transmitted infections

Although the risk of transfusion-transmitted infections today is lower than ever, the supply of safe blood products remains subject to contamination with known and yet to be identified human pathogens. Only continuous improvement and implementation of donor selection, sensitive screening tests and effective inactivation procedures can ensure the elimination, or at least reduction, of the risk of acquiring transfusion transmitted infections. In addition, ongoing education and up-to-date information regarding infectious agents that are potentially transmitted via blood components is necessary to promote the reporting of adverse events, an important component of transfusion transmitted disease surveillance. Thus, the collaboration of all parties involved in transfusion medicine, including national haemovigilance systems, is crucial for protecting a secure blood product supply from known and emerging blood-borne pathogens

Head and neck cancer surgery during the COVID-19 pandemic: An international, multicenter, observational cohort study

Background: The aims of this study were to provide data on the safety of head and neck cancer surgery currently being undertaken during the coronavirus disease 2019 (COVID-19) pandemic. Methods: This international, observational cohort study comprised 1137 consecutive patients with head and neck cancer undergoing primary surgery with curative intent in 26 countries. Factors associated with severe pulmonary complications in COVID-19–positive patients and infections in the surgical team were determined by univariate analysis. Results: Among the 1137 patients, the commonest sites were the oral cavity (38%) and the thyroid (21%). For oropharynx and larynx tumors, nonsurgical therapy was favored in most cases. There was evidence of surgical de-escalation of neck management and reconstruction. Overall 30-day mortality was 1.2%. Twenty-nine patients (3%) tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within 30 days of surgery; 13 of these patients (44.8%) developed severe respiratory complications, and 3.51 (10.3%) died. There were significant correlations with an advanced tumor stage and admission to critical care. Members of the surgical team tested positive within 30 days of surgery in 40 cases (3%). There were significant associations with operations in which the patients also tested positive for SARS-CoV-2 within 30 days, with a high community incidence of SARS-CoV-2, with screened patients, with oral tumor sites, and with tracheostomy. Conclusions: Head and neck cancer surgery in the COVID-19 era appears safe even when surgery is prolonged and complex. The overlap in COVID-19 between patients and members of the surgical team raises the suspicion of failures in cross-infection measures or the use of personal protective equipment. Lay Summary: Head and neck surgery is safe for patients during the coronavirus disease 2019 pandemic even when it is lengthy and complex. This is significant because concerns over patient safety raised in many guidelines appear not to be reflected by outcomes, even for those who have other serious illnesses or require complex reconstructions. Patients subjected to suboptimal or nonstandard treatments should be carefully followed up to optimize their cancer outcomes. The overlap between patients and surgeons testing positive for severe acute respiratory syndrome coronavirus 2 is notable and emphasizes the need for fastidious cross-infection controls and effective personal protective equipment

High sensitivity and negative predictive value of the DETECT algorithm for an early diagnosis of pulmonary arterial hypertension in systemic sclerosis: application in a single center

Abstract Background Pulmonary arterial hypertension (PAH) is one of the most relevant causes of death in systemic sclerosis. The aims of this study were to analyse the recently published DETECT algorithm comparing it with European Society of Cardiology/European Respiratory Society (ESC/ERS) 2009 guidelines: as screening of PAH; (2) identifying median pulmonary arterial pressure (mPAP) ≥21 mmHg; and (3) determining any group of pulmonary hypertension (PH). Methods Eighty-three patients fulfilling LeRoy’s systemic sclerosis diagnostic criteria with at least right heart catheterization were studied retrospectively. Clinical data, serological biomarkers, echocardiographic and hemodynamic features were collected. SPSS 20.0 was used for statistical analysis. Results According to right heart catheterization findings, 35 patients with PAH and 28 with no PH met the standards for DETECT algorithm analysis: 27.0% of patients presented with functional class III/IV. Applying DETECT, the sensitivity was 100%, specificity 42.9%, the positive predictive value 68.6% and the negative predictive value 100%, whereas employing the ESC/ERS guidelines these were 91.4%, 85.7%, 88.9% and 89.3%, respectively. There were no missed diagnoses of PAH using DETECT compared with three patients missed (8.5%) using ESC/ERS guidelines. The DETECT algorithm also showed greater sensitivity and negative predictive value to identify patients with mPAP ≥21 mmHg or with any type of PH. Conclusions The DETECT algorithm is confirmed as an excellent screening method due to its high sensitivity and negative predictive value, minimizing missed diagnosis of PAH. DETECT would be accurate either for early diagnosis of borderline mPAP or any group of PH