The prognostic impact of SIGLEC5-induced impairment of CD8+ T cell activation in sepsis.

BACKGROUND: Sepsis is associated with T-cell exhaustion, which significantly reduces patient outcomes. Therefore, targeting of immune checkpoints (ICs) is deemed necessary for effective sepsis management. Here, we evaluated the role of SIGLEC5 as an IC ligand and explored its potential as a biomarker for sepsis. METHODS: In vitro and in vivo assays were conducted to both analyse SIGLEC5's role as an IC ligand, as well as assess its impact on survival in sepsis. A multicentre prospective cohort study was conducted to evaluate the plasmatic soluble SIGLEC5 (sSIGLEC5) as a mortality predictor in the first 60 days after admission in sepsis patients. Recruitment included sepsis patients (n = 346), controls with systemic inflammatory response syndrome (n = 80), aneurism (n = 11), stroke (n = 16), and healthy volunteers (HVs, n = 100). FINDINGS: SIGLEC5 expression on monocytes was increased by HIF1α and was higher in septic patients than in healthy volunteers after ex vivo LPS challenge. Furthermore, SIGLEC5-PSGL1 interaction inhibited CD8+ T-cell proliferation. Administration of sSIGLEC5r (0.8 mg/kg) had adverse effects in mouse endotoxemia models. Additionally, plasma sSIGLEC5 levels of septic patients were higher than HVs and ROC analysis revealed it as a mortality marker with an AUC of 0.713 (95% CI, 0.656-0.769; p < 0.0001). Kaplan-Meier survival curve showed a significant decrease in survival above the calculated cut-off (HR of 3.418, 95% CI, 2.380-4.907, p < 0.0001 by log-rank test) estimated by Youden Index (523.6 ng/mL). INTERPRETATION: SIGLEC5 displays the hallmarks of an IC ligand, and plasma levels of sSIGLEC5 have been linked with increased mortality in septic patients. FUNDING: Instituto de Salud Carlos III (ISCIII) and "Fondos FEDER" to ELC (PIE15/00065, PI18/00148, PI14/01234, PI21/00869), CDF (PI21/01178), RLR (FI19/00334) and JAO (CD21/00059).

Comparison of strategies for adherence to venous thromboembolism prophylaxis in high-risk surgical patients: a before and after intervention study.

BACKGROUND: Venous thromboembolism (VTE) is a major cause of perioperative morbimortality. Despite significant efforts to advance evidence-based practice, prevention rates remain inadequate in many centres. OBJECTIVE: To evaluate the effectiveness of different strategies aimed at improving adherence to adequate VTE prophylaxis in surgical patients at high risk of VTE. METHOD: Before and after intervention study conducted at a tertiary hospital. Adherence to adequate VTE prophylaxis was compared according to three strategies consecutively implemented from January 2019 to December 2020. A dedicated hospitalist physician alone (strategy A) or in conjunction with a nurse (strategy B) overlooked the postoperative period to ensure adherence and correct inadequacies. Finally, a multidisciplinary team approach (strategy C) focused on promoting adequate VTE prophylaxis across multiple stages of care-from the operating room (ie, preoperative team-based checklist) to collaboration with clinical pharmacists in the postoperative period-was implemented. RESULTS: We analysed 2074 surgical patients: 783 from January to June 2019 (strategy A), 669 from July 2019 to May 2020 (strategy B), and 622 from June to December 2020 (strategy C). VTE prophylaxis adherence rates for strategies (A), (B) and (C) were (median (25th-75th percentile)) 43.29% (31.82-51.69), 50% (42.57-55.80) and 92.31% (91.38-93.51), respectively (p<0.001; C>A=B). There was a significant reduction in non-compliance on all analysed criteria (risk stratification (A (25.5%), B (22%), C (6%)), medical documentation (A (68%), B (55.2%) C (9%)) and medical prescription (A (51.85%), B (48%), C (6.10%)) after implementation of strategy C (p<0.05). Additionally, a significant increase in compliance with adequate dosage, dosing interval and scheduling of the prophylactic regimen was observed. CONCLUSION: Perioperative VTE prophylaxis strategies that relied exclusively on physicians and/or nurses were associated with suboptimal execution and prevention. A multidisciplinary team-based approach that covers multiple stages of patient care significantly increased adherence to adequate VTE prophylaxis in surgical patients at high risk of developing perioperative VTE.

EPICO 3.0. Management of non-neutropenic patients in medical wards.

BACKGROUND: Although the management of invasive fungal infection (IFI) has improved, a number of controversies persist regarding the approach to invasive fungal infection in non-neutropenic medical ward patients. AIMS: To identify the essential clinical knowledge to elaborate a set of recommendations with a high level of consensus necessary for the management of IFI in non-neutropenic medical ward patients. METHODS: A prospective, Spanish questionnaire, which measures consensus through the Delphi technique, was anonymously answered and e-mailed by 30 multidisciplinary national experts, all specialists (intensivists, anesthesiologists, microbiologists, pharmacologists and specialists in infectious diseases) in IFI and belonging to six scientific national societies. They responded to five questions prepared by the coordination group after a thorough review of the literature published in the last few years. For a category to be selected, the level of agreement among the experts in each category had to be equal to or greater than 70%. In a second round, 73 specialists attended a face-to-face meeting held after extracting the recommendations from the chosen topics, and validated the pre-selected recommendations and derived algorithm. RESULTS: The following recommendations were validated and included in the algorithm: 1. several elements were identified as risk factors for invasive candidiasis (IC) in non-hematologic medical patients; 2. no agreement on the use of the colonization index to decide whether prescribing an early antifungal treatment to stable patients (no shock), with sepsis and no other evident focus and IC risk factors; 3. agreement on the use of the Candida Score to decide whether prescribing early antifungal treatment to stable patients (no shock) with sepsis and no other evident focus and IC risk factors; 4. agreement on initiating early antifungal treatment in stable patients (no shock) with a colonization index>0.4, sepsis with no other evident focus and IC risk factors; 5. agreement on the performance of additional procedures in stable patients (no shock) with sepsis and no other evident focus, IC risk factors, without colonization index>0.4, but with a high degree of suspicion. CONCLUSIONS: Based on the expert's recommendations, an algorithm for the management of non-neutropenic medical patients was constructed and validated. This algorithm may be useful to support bedside prescription.