Abnormal bone architecture in mice expressing MyD88 in cells of the osteoclast lineage.

The adapter protein myeloid differentiation primary response gene 88 (MyD88) links the intracellular domains of interleukin receptors 1 and 18, and most Toll-like receptors (TLRs) to interleukin 1 receptor associated kinase (IRAK) signaling and subsequent NF-κB-mediated transcription. Previous work showed that mice with global deficiency of MyD88 (MyD88-/-) have osteopenic cancellous bone along with a reduction in osteoblastic but also osteoclastic surfaces. To further elucidate the role of MyD88 in bone, we utilized mice with osteoclast-restricted MyD88 expression in bone (MyD88OC). Bones of MyD88OC and wild type (wt) mice were examined by microCT analysis. Mechanical properties of bones were tested by three-point bending, and gene expression measured using quantitative real-time polymerase chain reaction. In MyD88OC mice, no osteopenic traits were observed, however, a drastic reduction in geometric parameters was detected. In trabecular bone a loss of connectivity density (-44%, p less than 0.0001) was measured and in cortical bone Imax (-31%, p less than 0.0001), Imin (-20%, p less than 0.001), J (-26%, p less than 0.0001) were reduced. Mechanical testing showed increased load to failure (77%, p less than 0.01) and decreased deflection at failure (-68%, p less than 0.01) of the femur. On the molecular level, relative gene expression analysis showed a (-29%, p less than 0.01) reduction in receptor activator of nuclear factor κ B ligand (RANKL) and no difference in osteoprotegerin (OPG) or RANK. Further, the bone resorption markers cathepsin K (CTSK) and tartrate-resistant acid phosphatase 5 (TRAP) were unchanged. In contrast, the bone formation markers collagen type 1 (COL1A1) and osteocalcin (OC) were decreased by -72% (p less than 0.0001) and -82% (p less than 0.0001), respectively. Together, our data suggests that the function of MyD88 in osteoclasts is sufficient to maintain bone mass, while it fails to preserve bone geometry, likely through dysfunctions in osteoblasts.

Basilar artery occlusion: drip-and-ship versus direct-to-center for mechanical thrombectomy within the Neurovascular Network of Southwest Bavaria (NEVAS).

BACKGROUND: Recent clinical trials revealed a substantial clinical benefit for mechanical thrombectomy (MT) in patients with basilar artery occlusion (BAO). While urban areas are sufficiently covered with comprehensive stroke centers and MT expertise, rural areas lack such resources. Structured telemedical stroke networks offer rural hospitals instant consultation by stroke experts, enabling swift administration of intravenous thrombolysis (IVT) on-site and transportation for MT. For BAO patients, data on performance and clinical outcomes in telemedical stroke networks are lacking. METHODS: We retrospectively analyzed data from patients with acute BAO eligible for MT: those treated directly in our comprehensive stroke center (direct-to-center/DC) and those treated in rural hospitals that were telemedically consulted by the Neurovascular Network of Southwest Bavaria (NEVAS) and transferred to our center for MT (drip-and-ship, DS). Key time intervals, stroke management performance and functional outcome after 90 days were compared. RESULTS: Baseline characteristics, including premorbid status and stroke severity, were comparable. Time from symptom onset to IVT was identical in both groups (118 min). There was a delay of 180 min until recanalization in DS patients, mainly due to patient transport for MT. Procedural treatment time intervals, success of recanalization and complications were comparable. Clinical outcome at 3 months follow-up of DS patients was not inferior to DC patients. CONCLUSION: We show for the first time that patients with BAO in rural areas benefit from a structured telemedicine network such as NEVAS, regarding both on-site processing and drip-and-ship for MT. Clinical outcomes are comparable among DS and DC patients.