Patterns of pseudoprogression across different cancer entities treated with immune checkpoint inhibitors.

BACKGROUND: Pseudoprogression (PsPD) is a rare response pattern to immune checkpoint inhibitor (ICI) therapy in oncology. This study aims to reveal imaging features of PsPD, and their association to other relevant findings. METHODS: Patients with PsPD who had at least three consecutive cross-sectional imaging studies at our comprehensive cancer center were retrospectively analyzed. Treatment response was assessed according to immune Response Evaluation Criteria in Solid Tumors (iRECIST). PsPD was defined as the occurrence of immune unconfirmed progressive disease (iUPD) without follow-up confirmation. Target lesions (TL), non-target lesions (NTL), new lesions (NL) were analyzed over time. Tumor markers and immune-related adverse events (irAE) were correlated. RESULTS: Thirty-two patients were included (mean age: 66.7 ± 13.6 years, 21.9% female) with mean baseline STL of 69.7 mm ± 55.6 mm. PsPD was observed in twenty-six patients (81.3%) at FU1, and no cases occurred after FU4. Patients with iUPD exhibited the following: TL increase in twelve patients, (37.5%), NTL increase in seven patients (21.9%), NL appearance in six patients (18.8%), and combinations thereof in four patients (12.5%). The mean and maximum increase for first iUPD in sum of TL was 19.8 and 96.8 mm (+ 700.8%). The mean and maximum decrease in sum of TL between iUPD and consecutive follow-up was - 19.1 mm and - 114.8 mm (-60.9%) respectively. The mean and maximum sum of new TL at first iUPD timepoint were 7.6 and 82.0 mm respectively. In two patients (10.5%), tumor-specific serologic markers were elevated at first iUPD, while the rest were stable or decreased among the other PsPD cases (89.5%). In fourteen patients (43.8%), irAE were observed. CONCLUSIONS: PsPD occurred most frequently at FU1 after initiation of ICI treatment. The two most prevalent reasons for PsPD were TL und NTL progression, with an increase in TL diameter commonly below + 100%. In few cases, PsPD was observed even if tumor markers were rising compared to baseline. Our findings also suggest a correlation between PsPD and irAE. These findings may guide decision-making of ICI continuation in suspected PsPD.

Imaging of the degenerative spine using a sagittal T2-weighted DIXON turbo spin-echo sequence.

PURPOSE: To evaluate the diagnostic performance of a sagittal T2-weighted DIXON turbo spin-echo (TSE) sequence and to assess whether fat-only images could replace dedicated sagittal T1-weighted sequences for magnetic resonance imaging (MRI) of the degenerative spine. METHOD: 35 patients (56.5 ± 19.8 years, 62.9 % males) with lumbar back pain (LBP) who underwent MRI of the lumbar spine including a sagittal T2-weighted DIXON sequence (acquisition time: 3:25 min) and T1-weighted sequence (acquisition time: 3:03 min) were included. Two image layouts (layout 1: fat-only AND water-only AND in-phase images of the DIXON sequence; layout 2: water-only AND in-phase images of the DIXON sequence AND T1-weighted images) were evaluated by two readers (R1 and R2) concerning degenerative changes including diagnostic confidence (1 - low, 2 - intermediate, and 3 - high) and signal changes of vertebral bone marrow (BM). Results were compared between readers and layouts. RESULTS: No differences were observed in the number of detected pathologies on a segment-wise level, nor in the number of segments affected by degenerative changes when comparing evaluations of layout 1 and layout 2 for each reader. Diagnostic confidence was high without a statistically significant difference between the readings of both layouts (R1: layout 1: 2.79 ± 0.41, layout 2: 2.81 ± 0.39, p = 0.53; R2: layout 1: 2.99 ± 0.07, layout 2: 2.99 ± 0.07, p = 0.99). CONCLUSIONS: In patients with LBP, MRI using a sagittal T2-weighted DIXON sequence and no separate T1-weighted sequence might be sufficient to accurately detect common degenerative changes with high diagnostic confidence. Sparing dedicated T1-weighted sequences can considerably reduce overall scan time.

Endovascular Stroke Treatment on Single-Plane vs. Bi-Plane Angiography Suites : Technical Considerations and Evaluation of Treatment Success.

INTRODUCTION: Endovascular stroke therapy is mostly available in comprehensive stroke centers with state of the art bi-plane angiography suites. The aim of the present study was to analyze if it is justifiable to treat patients with alternative x­ray machines in the case of capacity constraints, or if it is mandatory to refer patients in such cases. Secondly, we wanted to draw conclusions for the feasibility of different logistic approaches in stroke treatment, such as a "helistroke" concept. METHODS: This was a retrospective dual center analysis of all patients treated on a single-plane angiography suite between 2009 and 2017. A propensity scored matching analysis at a 1:3 ratio was performed with patients treated on a bi-plane angiography suite to receive homogeneous groups. RESULTS: A total of 42 patients were treated on a single-plane angiography suite and were compared to 126 patients treated on a bi-plane angiography suite. No significant differences in technical parameters, procedure times, recanalization success and complications could be detected. Also, there was no difference in the clinical outcome between the two groups. The only significant difference was the higher amount of radiation dose used on the bi-plane angiography machines to achieve the final results (205,660 mGy × cm2 vs. 114,565 mGy × cm2; p < 0.001). DISCUSSION: In an era of an ever-changing stroke infrastructure and an increasing demand in thrombectomy procedures, it is feasible and safe for experienced neurointerventionalists to perform endovascular stroke procedures on single-plane angiography units.

PROTECT: PRoximal balloon Occlusion TogEther with direCt Thrombus aspiration during stent retriever thrombectomy - evaluation of a double embolic protection approach in endovascular stroke treatment.

PURPOSE: Stent retriever-based mechanical thrombectomy (MT) for emergent large vessel occlusions (ELVO) is often complicated by thrombus fragmentation causing distal embolization and embolization to new vascular territories. Well-established embolic protection approaches include proximal flow arrest and distal aspiration techniques during stent retriever maneuvers. Aiming at the reduction of thrombus fragmentation during MT we evaluated a technical approach combining proximal balloon occlusion together with direct thrombus aspiration during MT: the PROTECT technique. METHODS: We performed a case-control study comparing the PROTECT technique with sole distal aspiration during MT regarding technical and procedural parameters, n=200 patients with ELVO of either the terminus of the internal carotid artery or the proximal middle artery were included. RESULTS: PROTECT resulted in a shorter procedure time (29 vs 40 min; P=0.002), in a higher rate of successful recanalizations (100% vs 78%; P=0.001) and a higher rate of complete reperfusions (70% vs 39%; P<0.001) compared with sole distal aspiration during MT. CONCLUSION: The PROTECT technique is a promising new approach to significantly reduce thrombus fragmentation and, hence distal embolization during MT. This safe and efficient technique needs to be validated in larger trials to confirm our results.

JAGN1 deficiency causes aberrant myeloid cell homeostasis and congenital neutropenia.

The analysis of individuals with severe congenital neutropenia (SCN) may shed light on the delicate balance of factors controlling the differentiation, maintenance and decay of neutrophils. We identify 9 distinct homozygous mutations in the JAGN1 gene encoding Jagunal homolog 1 in 14 individuals with SCN. JAGN1-mutant granulocytes are characterized by ultrastructural defects, a paucity of granules, aberrant N-glycosylation of multiple proteins and increased incidence of apoptosis. JAGN1 participates in the secretory pathway and is required for granulocyte colony-stimulating factor receptor-mediated signaling. JAGN1 emerges as a factor that is necessary in the differentiation and survival of neutrophils.