Cardiac fibrosis is a major driver of heart failure, a leading cause of morbidity and mortality worldwide. Advances in single-cell transcriptomics have revealed the pivotal role of SPP1+ macrophages in the pathogenesis of cardiac fibrosis, positioning them as critical mediators and promising therapeutic targets. SPP1+ macrophages, characterized by elevated expression of secreted phosphoprotein 1 (SPP1) and often co-expressing Triggering Receptor Expressed on Myeloid Cells 2 (TREM2), localize to fibrotic niches in the heart and other organs. These cells interact with activated fibroblasts and myofibroblasts, driving extracellular matrix remodeling and fibrosis progression. Their differentiation is orchestrated by signals such as CXCL4, GM-CSF, and IL-17A, further emphasizing their regulatory complexity. Therapeutic strategies targeting SPP1+ macrophages have shown encouraging preclinical results. Approaches include silencing Spp1 using antibody–siRNA conjugates and modulating key pathways involved in macrophage differentiation. These interventions have effectively reduced fibrosis and improved cardiac function in animal models. The mechanisms underlying SPP1+ macrophage function in cardiac fibrosis provide a foundation for innovative therapies aimed at mitigating pathological remodeling and improving outcomes in patients with heart failure. This emerging field has significant potential to transform the treatment of fibrotic heart disease.

BACKGROUND: During the surge in coronavirus disease 2019 (COVID-19) infections in early 2020, many medical organisations began developing strategies for implementing teleconsultation to maintain medical services during lockdown and to limit physical contact. Therefore, we developed a teleconsultation preoperative evaluation platform to replace on-site preoperative meetings. OBJECTIVE: This study assessed the feasibility of a teleconsultation for preoperative evaluation and procedure-associated adverse events. DESIGN: Implementation study. SETTING: A tertiary care university hospital in Germany from April 2020 to October 2020. PATIENTS: One hundred and eleven patients scheduled for elective surgery. INTERVENTION: Patients were assigned to receive teleconsultation for preoperative evaluation and to complete a subsequent survey. MAIN OUTCOME MEASURES: Primary endpoints were medical and technical feasibility, user satisfaction and time savings. RESULTS: For 100 out of 111 patients, telepreoperative consultations allowed for adequate perioperative risk assessment, patient education and also for effective collection of legal signatures. For six patients (5.4%), consultations could not be started because of technical issues, whereas for five patients (4.8%), clearance for surgery could not be granted because of medical reasons. A clear majority of anaesthetists (93.7%) rated the telepreoperative evaluations as equivalent to on-site meetings. The majority of the patients considered teleconsultation for preoperative evaluation as convenient as an on-site meeting (98.2%) and would choose a teleconsultation again (97.9%). Median travel time saved by patients was 60 min (Q1 40, Q3 80). We registered one adverse event: we detected atrial fibrillation in one patient only immediately prior to surgery. CONCLUSION: Telepreoperative evaluations are medically and technically feasible, yielding high satisfaction rates on both sides. However, regarding patient safety, not every patient is equally well suited. Overall, implementation of teleconsultation for preoperative evaluation into clinical routine could help maintain medical care during the COVID-19 pandemic. TRIAL REGISTRATION: NCT04518514, ClinicalTrials.gov

Background: Andexanet alfa is a specific antidote for factor Xa (FXa) inhibitors. It is licensed to treat patients under FXa inhibitor therapy with life-threatening bleeding. Concomitantly, volume expanders are used to compensate for blood loss and maintain circulation. The competitive binding of andexanet to FXa inhibitors may be disrupted due to hemodilution, as shown by laboratory assays with high sample dilution. This study investigated the efficacy of andexanet for the reversal of FXa inhibitors under hemodilution. Methods: Blood from 10 healthy volunteers was anticoagulated with rivaroxaban and subsequently treated with four different volume expanders (Ringer’s solution, 4% gelatine, 5% and 20% human albumin (HA)) at two dilution levels (20% and 50%). After anticoagulation and hemodilution, andexanet was added according to the high-dose protocol. Blood samples were analyzed using a Russell’s viper venom (RVV) test on a Clot Pro^® device, a thrombin generation assay, a fully automated coagulation analyzer and a chromogenic anti-FXa activity assay. Results: After anticoagulation, the median rivaroxaban concentration was 272 ng/mL (IQR 254–353). Anticoagulation with rivaroxaban caused a significant impairment of all coagulation parameters, which was further aggravated by hemodilution. After the administration of andexanet, coagulation parameters in anticoagulated samples were reversed to near baseline in all groups. Andexanet administration decreased the rivaroxaban plasma concentration in all groups to a median of <10 ng/mL. In the anticoagulated, non-hemodiluted samples, anti-FXa activity was reduced by 98%. The anti-FXa activity in the anticoagulated, hemodiluted samples was reduced by approximately 96% in the 20% diluted samples and by about 93% in the 50% diluted samples. Conclusions: Our data indicate that FXa inhibitor reversal with andexanet is about 5% less effective with 50% hemodilution than in non-hemodiluted samples.