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.

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.

Due to our ageing population, the number of elderly patients who are treated in the emergency department due to low-energy trauma (e.g., tripping) continues to rise. These minor accidents often result in fragility fractures classically located in the proximal humerus, distal radius, spine, pelvis, and near the hip joint. Pre-existing conditions, polypharmacy, and general frailty increase the risk of fragility fractures in this patient population.

Geriatric trauma fractures and especially insufficiency fractures of the posterior pelvic ring are often difficult to diagnose by plain X‑ray. Therefore, in geriatric trauma patients, cross-sectional imaging, e.g., computed tomography (CT), dual-energy CT (DECT), or magnetic resonance imaging (MRI), should be considered early for reliable evaluation of a suspected fracture. This also allows for the identification of older fractures. Particularly in cognitively impaired elderly patients, difficult examination conditions or an unclear fall event, cross-sectional imaging is often indicated. However, this may also involve risks, e.g., use of contrast medium in patients with impaired renal function, so that each case must be considered individually. Furthermore, the diagnosis and treatment of osteoporosis, which is an underlying disease that leads to fragility fractures, is of particular importance. In the diagnostic workup, measurement of bone density using dual energy X‑ray absorptiometry (DXA) is the standard method according to guidelines. In specific situations, high-resolution peripheral quantitative CT (HR-pQCT) may also be used.

Due to the special challenges of correctly detecting fragility fractures and being able to quickly initiate adequate therapy, good cooperation between radiologists and trauma surgeons is necessary.