Klinikum Hochsauerland GmbH

Effective longitudinal biomarkers that track disease progression are needed to characterize the presymptomatic phase of genetic frontotemporal dementia (FTD). We investigate the utility of cerebral perfusion as one such biomarker in presymptomatic FTD mutation carriers.

We investigated longitudinal profiles of cerebral perfusion using arterial spin labeling magnetic resonance imaging in 42 C9orf72, 70 GRN, and 31 MAPT presymptomatic carriers and 158 non‐carrier controls. Linear mixed effects models assessed perfusion up to 5 years after baseline assessment.

Perfusion decline was evident in all three presymptomatic groups in global gray matter. Each group also featured its own regional pattern of hypoperfusion over time, with the left thalamus common to all groups. Frontal lobe regions featured lower perfusion in those who symptomatically converted versus asymptomatic carriers past their expected age of disease onset.

Cerebral perfusion is a potential biomarker for assessing genetic FTD and its genetic subgroups prior to symptom onset.

Gray matter perfusion declines in at‐risk genetic frontotemporal dementia (FTD).Regional perfusion decline differs between at‐risk genetic FTD subgroups .Hypoperfusion in the left thalamus is common across all presymptomatic groups.Converters exhibit greater right frontal hypoperfusion than non‐converters past their expected conversion date.Cerebral hypoperfusion is a potential early biomarker of genetic FTD.

Summary: Background: Intravascular ultrasound (IVUS)-guided percutaneous transluminal angioplasty (PTA) might offer clinical benefits compared to angiography-guided PTA in patients with peripheral artery disease (PAD). A cost-effectiveness model was developed to examine the benefits and costs of IVUS-guided PTA versus angiography-guided PTA in PAD patients with femoropopliteal (FP) occlusive disease. Methods: A two-step model (a one-year decision tree followed by a lifetime semi-Markov model) was developed from a German healthcare payer perspective to estimate the costs and outcomes over a one-year and lifetime horizon. Clinical events included target lesion revascularization (TLR), amputation, and death. Transition probabilities and utility values were derived from published literature. Healthcare costs were based on German Diagnosis Related Groups (DRG) codes. Costs and outcomes were discounted at a rate of 3% per year. The incremental cost-effectiveness ratio (ICER) was calculated, and sensitivity analyses were performed to assess the robustness of the results. Results: In the one-year horizon, IVUS-guided PTA resulted in incremental quality-adjusted life-years (QALY) and costs of 0.02 and €919 per patient respectively, with a corresponding ICER of €45,195/QALY gained versus angiography-guided PTA. In the lifetime horizon, IVUS-guided PTA outperforms angiography-guided PTA; it was associated with a cost saving of €46 per patient and incremental QALY of 0.22. Utility value for post-TLR, as well as probabilities of death and TLR had the greatest impact on the one-year ICER, while cost of TLR and probabilities of TLR and amputation influenced the lifetime ICER most. The probability of IVUS-guided PTA being cost-effective at a willingness-to-pay (WTP) threshold of €50,000/QALY was 50.4% in the one-year horizon and increased to 85.9% in the lifetime horizon. Conclusions: In this analysis IVUS-guided PTA among patients with symptomatic FP atherosclerosis was cost-saving in a lifetime horizon from the German healthcare payer perspective.

The von Willebrand factor-directed nanobody caplacizumab has greatly changed the treatment of immune thrombotic thrombocytopenic purpura (iTTP) in recent years. Data from randomized controlled trials established efficacy and safety.

This study aims to address open questions regarding patient selection, tailoring of therapy duration, obstacles in prescribing caplacizumab in iTTP, effect on adjunct treatment, and outcomes in the real-world setting.

We report retrospective, observational cohorts of 113 iTTP episodes treated with caplacizumab and 119 historical control episodes treated without caplacizumab. We aggregated data from the caplacizumab phase II/III trials and real-world data from France, the United Kingdom, Germany, and Austria (846 episodes, 396 treated with caplacizumab, and 450 historical controls).

Caplacizumab was efficacious in iTTP, independent of the timing of therapy initiation, but curtailed the time of active iTTP only when used in the first-line therapy within 72 hours after diagnosis and until at least partial ADAMTS13-activity remission. Aggregated data from multiple study populations showed that caplacizumab use resulted in significant absolute risk reduction of 2.87% for iTTP-related mortality (number needed to treat 35) and a relative risk reduction of 59%.

Caplacizumab should be used in first line and until ADAMTS13-remission, lowers iTTP-related mortality and refractoriness, and decreases the number of daily plasma exchange and hospital stay. This trial is registered at www.

gov as #NCT04985318.