Search

The failure to halt the global decline in biodiversity by 2020 contributed to the adoption of the ambitious Kunming-Montreal Global Biodiversity Framework, which includes transparency and responsibility as foundations. The Global Biodiversity Framework identifies the actions needed so that societies are living in harmony with nature by 2050. To support the delivery of this ambition, the transparency and responsibility mechanisms defined in the Global Biodiversity Framework include a detailed Monitoring Framework designed to prompt evidence-based actions and track progress towards its goals and targets at the national and global level. The Monitoring Framework includes a set of indicators selected by the Parties through a political process. These indicators have since been operationalized through a scientific process led by an expert group focused on assessing and clarifying their methods. Most indicators are now ready to inform on progress, but key limitations of data availability and methodological challenges remain. The onus is now on the Parties to resource implementation and on the scientific community to support indicator use and development. Implementation of the Monitoring Framework will provide an unprecedented view of the state of biodiversity at the national level, which can be used to assess both national and global progress. Investment to overcome the Monitoring Framework's weaknesses will improve our ability to measure progress and mobilize the actions needed to protect and restore biodiversity and the many benefits we receive from nature., Competing Interests: Competing interests: Multiple authors are or were employed by organizations involved in the negotiation process: at the time of writing, F.A. and J.E.C. were employed by the Secretariat of the CBD, J.M.W. was part of the United Kingdom of Great Britain and Northern Ireland delegation and co-chair of the AHTEG, M.C.L. was part of the Colombia delegation and co-chair of the AHTEG, and A.G. was co-chair of GEO BON, an observer organization to the CBD and member of the AHTEG. All authors were acting in a non-political capacity when conducting the work on the Monitoring Framework., (© 2024. Springer Nature Limited.)

Background & Aims: In primary biliary cholangitis (PBC), static liver stiffness measurement (LSM) has proven prognostic value. However, the added prognostic value of LSM time course in this disease remains uncertain., Methods: We conducted an international retrospective cohort study among patients with PBC treated with ursodeoxycholic acid and followed by vibration-controlled transient elastography between 2003 and 2022. Using joint modeling, the association of LSM trajectory and the incidence of serious clinical events (SCE), defined as cirrhosis complications, liver transplantation, or death, was quantified using the hazard ratio and its confidence interval., Results: A total of 6362 LSMs were performed in 3078 patients (2007 on ursodeoxycholic acid alone; 13% with cirrhosis), in whom 316 SCE occurred over 14,445 person-years (median follow-up, 4.2 years; incidence rate, 21.9 per 1000 person-years). LSM progressed in 59% of patients (mean, 0.39 kPa/year). After adjusting for prognostic factors at baseline, including LSM, any relative change in LSM was associated with a significant variation in SCE risk (P < .001). For example, the adjusted hazard ratios (95% confidence interval) associated with a 20% annual variation in LSM were 2.13 (1.89-2.45) for the increase and 0.40 (0.33-0.46) for the decrease. The association between LSM trajectory and SCE risk persisted regardless of treatment response or duration, when patients with cirrhosis were excluded, and when only death or liver transplantation was considered., Conclusions: Tracking longitudinal changes in LSM using vibration-controlled transient elastography provides valuable insights into PBC prognosis, offering a robust predictive measure for the risk of SCE. LSM could be used as a clinically relevant surrogate end point in PBC clinical trials., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background & Aims: Successful immunosuppression withdrawal (ISW) is possible for a subfraction of liver transplant (LT) recipients but the factors that define the risk of ISW failure are largely unknown. One candidate prognostic factor for ISW success or operational tolerance (OT) is longer time between LT and ISW which we term "pre-withdrawal time". To clarify the impact of pre-withdrawal time span on subsequent ISW success or failure, we conducted a systematic review with meta-analysis., Methods: We systematically interrogated the literature for LT recipient ISW studies reporting pre-withdrawal time. Eligible articles from Embase, Medline, and the Cochrane Central Register of Controlled Trials were used for backward and forward citation searching. Pre-withdrawal time individual patient data (IPD) was requested from authors. Pooled mean differences and time-response curves were calculated using random-effects meta-analyses., Results: We included 17 studies with 691 patients, 15 of which (620 patients) with IPD. Study-level risk of bias was heterogeneous. Mean pre-withdrawal time was greater by 427 days [95% confidence interval (CI) 67-788] in OT compared to non-OT patients. This increase was potentiated to 799 days (95% CI 369-1229) or 1074 days (95% CI 685-1463) when restricting analysis to adult or European study participants. In time-response meta-analysis for adult or European ISW candidates, likelihood of OT increased by 7% (95% CI 4-10%) per year after LT (GRADE low- and moderate-certainty of evidence, respectively)., Conclusions: Our data support the impact of pre-withdrawal time in ISW decision-making for adult and European LT recipients., Prospero Registration: CRD42021272995., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The biofilm matrix is composed of exopolysaccharides, eDNA, membrane vesicles, and proteins. While proteomic analyses have identified numerous matrix proteins, their functions in the biofilm remain understudied compared to the other biofilm components. In the Pseudomonas aeruginosa biofilm, several studies have identified OprF as an abundant matrix protein and, more specifically, as a component of biofilm membrane vesicles. OprF is a major outer membrane porin of P. aeruginosa cells. However, current data describing the effects of OprF in the P. aeruginosa biofilm are limited. Here, we identify a nutrient-dependent effect of OprF in static biofilms, whereby Δ oprF cells form significantly less biofilm than wild type when grown in media containing glucose or low sodium chloride concentrations. Interestingly, this biofilm defect occurs during late static biofilm formation and is not dependent on the production of PQS, which is responsible for outer membrane vesicle production. Furthermore, while biofilms lacking OprF contain approximately 60% less total biomass than those of wild type, the number of cells in these two biofilms is equivalent. We demonstrate that P. aeruginosa Δ oprF biofilms with reduced biofilm biomass contain less eDNA than wild-type biofilms. These results suggest that the nutrient-dependent effect of OprF is involved in the maintenance of P. aeruginosa biofilms by retaining eDNA in the matrix. IMPORTANCE Many pathogens form biofilms, which are bacterial communities encased in an extracellular matrix that protects them against antibacterial treatments. The roles of several matrix components of the opportunistic pathogen Pseudomonas aeruginosa have been characterized. However, the effects of P. aeruginosa matrix proteins remain understudied and are untapped potential targets for antibiofilm treatments. Here, we describe a conditional effect of the abundant matrix protein OprF on late-stage P. aeruginosa biofilms. A Δ oprF strain formed significantly less biofilm in low sodium chloride or with glucose. Interestingly, the defective Δ oprF biofilms did not exhibit fewer resident cells but contained significantly less extracellular DNA (eDNA) than wild type. These results suggest that OprF is involved in matrix eDNA retention in biofilms., Competing Interests: The authors declare no conflict of interest.

Objectives: Bioprosthetic valve thrombosis has been considered uncommon, but recent studies have shown that it is more frequent than previously thought. Insufficient washout of the aortic sinus is believed to be a risk factor for bioprosthetic valve thrombosis. The objective of this in vitro experiment was to investigate the impact of aortic root morphology on blood flow in the aortic sinus and to relate these results to in vivo data obtained in patients with a transcatheter aortic valve implant., Methods: Two compliant aortic root phantoms with different morphologies (symmetrical and patient-specific) were fabricated with silicone. A bioprosthetic aortic valve was inserted in both phantoms. Haemodynamic measurements were performed in a pulsatile flow-loop replicating physiological flow and pressure conditions. The flow in the aortic root was visualized by injecting contrast agent (CA). The distribution of the CA was captured by a high-speed camera, and image post-processing was performed to quantify CA distribution in the aortic sinus. The results were compared with angiographic images after a transcatheter aortic valve implant., Results: Blood flow in the aortic root and the washout of the sinus portion are significantly affected by aortic root morphology. CA arrives at the aortic sinus of the 2 phantoms at 0.09 s and 0.16 s after the valve opens in the symmetrical and the patient-specific phantoms, respectively. Delayed CA arrival was also observed in the patients with a transcatheter aortic valve implant., Conclusions: Aortic root morphology affects the blood flow in the aortic sinus and may be a factor in bioprosthetic valve thrombosis. Therefore, patient-specific aortic root morphology should be considered when selecting and positioning a prosthesis.

To evaluate internal tandem duplication (ITD) insertion sites and length as well as their clinical impact in younger adult patients with FLT3-ITD-positive acute myeloid leukemia (AML), sequencing after DNA-based amplification was performed in diagnostic samples from 241 FLT3-ITD-mutated patients. All patients were treated on 3 German-Austrian AML Study Group protocols. Thirty-four of the 241 patients had more than 1 ITD, leading to a total of 282 ITDs; the median ITD length was 48 nucleotides (range, 15-180 nucleotides). ITD integration sites were categorized according to functional regions of the FLT3 receptor: juxtamembrane domain (JMD), n = 148; JMD hinge region, n = 48; beta1-sheet of the tyrosine kinase domain-1 (TKD1), n = 73; remaining TKD1 region, n = 13. ITD length was strongly correlated with functional regions (P < .001). In multivariable analyses, ITD integration site in the beta1-sheet was identified as an unfavorable prognostic factor for achievement of a complete remission (odds ratio, 0.22; P = .01), relapse-free survival (hazard ratio, 1.86; P < .001), and overall survival (hazard ratio, 1.59; P = .008). ITD insertion site in the beta1-sheet appears to be an important unfavorable prognostic factor in young adult patients with FLT3-ITD-positive AML. The clinical trials described herein have been registered as follows: AML HD93 (already published in 2003), AML HD98A (NCT00146120; http://www.ClinicalTrials.gov), and AMLSG 07-04 (NCT00151242; http://www.ClinicalTrials.gov).