High-pitch CT pulmonary angiography (CTPA) with ultra-low contrast medium volume for the detection of pulmonary embolism: a comparison with standard CTPA.

OBJECTIVE: To investigate the feasibility and image quality of high-pitch CT pulmonary angiography (CTPA) with reduced iodine volume in normal weight patients. METHODS: In total, 81 normal weight patients undergoing CTPA for suspected pulmonary arterial embolism were retrospectively included: 41 in high-pitch mode with 20 mL of contrast medium (CM); and 40 with normal pitch and 50 mL of CM. Subjective image quality was assessed and rated on a 3-point scale. For objective image quality, attenuation and noise values were measured in all pulmonary arteries from the trunk to segmental level. Contrast-to-noise ratio (CNR) was calculated. Radiation dose estimations were recorded. RESULTS: There were no statistically significant differences in patient and scan demographics between high-pitch and standard CTPA. Subjective image quality was rated good to excellent in over 90% of all exams with no significant group differences (p = 0.32). Median contrast opacification was lower in high-pitch CTPA (283.18 [216.06-368.67] HU, 386.81 [320.57-526.12] HU; p = 0.0001). CNR reached a minimum of eight in all segmented arteries, but was lower in high-pitch CTPA (8.79 [5.82-12.42], 11.01 [9.19-17.90]; p = 0.005). Median effective dose of high-pitch CTPA was lower (1.04 [0.72-1.27] mSv/mGy·cm; 1.49 [1.07-2.05] mSv/mGy·cm; p < 0.0001). CONCLUSION: High-pitch CTPA using ultra-low contrast volume (20 mL) rendered diagnostic images for the detection of pulmonary arterial embolism in most instances. Compared to standard CTPA, the high-pitch CTPA exams with drastically reduced contrast medium volume had also concomitantly reduced radiation exposure. However, objective image quality of high-pitch CTPA was worse, though likely still within acceptable limits for confident diagnosis. CLINICAL RELEVANCE: This study provides valuable insights on the performance of a high-pitch dual-source CTPA protocol, offering potential benefits in reducing contrast medium and radiation dose while maintaining sufficient image quality for accurate diagnosis in patients suspected of pulmonary embolism. KEY POINTS: • High-pitch CT pulmonary angiography (CTPA) with ultra-low volume of contrast medium and reduced radiation dose renders diagnostic examinations with comparable subjective image quality to standard CTPA in most patients. • Objective image quality of high-pitch CTPA is reduced compared to standard CTPA, but contrast opacification and contrast-to-noise ratio remain above diagnostic thresholds. • Challenges of high-pitch CTPA may potentially be encountered in patients with severe heart failure or when performing a Valsalva maneuver during the examination.

A multicenter real-world evidence study in the Swiss treatment landscape of chronic myeloid leukemia.

BACKGROUND: The real-world experience of Swiss chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs) is largely unknown, in particular with regard to achievement of response per European Leukemia Net (ELN) criteria and adherence to ELN recommendations. METHODS: This was a retrospective, non-interventional, multicenter chart review of patients with newly diagnosed CML who had received first-line TKI and were solely treated with TKIs between 2010 and 2015, with a minimum follow-up of 18 months, at six Swiss hospitals. Effectiveness was evaluated according to ELN 2013 milestone achievements at 3, 6, 12 and 18 months, and at last follow-up. RESULTS: Data from 63 patients (56% men; median age at diagnosis 55 years) were collected (first-line imatinib [n = 27], nilotinib [n = 27], dasatinib [n = 8], or ponatinib [n = 1]). TKI switches (49 times) and dosing changes (165 times) due to intolerance or insufficient response were frequent. Compared with patients receiving first-line imatinib, a higher proportion of patients receiving first-line nilotinib or dasatinib achieved optimal response at all timepoints, irrespective of subsequent TKI therapy, and a higher proportion of patients treated with first-line nilotinib and dasatinib reached deep molecular response (BCR-ABL1IS ≤ 0.01%) at 18 months (42 and 38%, respectively, versus 27%). Patients who received nilotinib or dasatinib switched therapies less frequently than patients treated with imatinib, irrespective of subsequent TKI therapy. CONCLUSIONS: Although patient numbers were small, this real-world evidence study with patients with CML confirms that ELN guidelines are generally implemented in Swiss clinical practice, with a large proportion of patients achieving ELN 2013 milestones. While TKI use involved all inhibitors approved at the time of the study, an unexpectedly high number of TKI therapy switches suggests a clear difference in TKI use between registration trials and clinical practice.

Segmentation and characterization of visceral and abdominal subcutaneous adipose tissue on CT with and without contrast medium: influence of 2D- and 3D-segmentation.

BACKGROUND: Adipose tissue is a valuable biomarker. Although validation and correlation to clinical data have mostly been performed on non-enhanced scans (NES), a previous study has shown conversion of values of contrast enhanced scan (CES) into those of NES to be feasible with segmentation of the entire abdomen (3D-segmentation). In this study we analyzed if density and area of abdominal adipose tissue segmented in a single slice (2D-segmentation) of CES may be converted into that of NES. Furthermore, we compared the precision of conversion between 2D- and 3D-segmentation. METHODS: Thirty-one multi-phasic abdominal CT examinations at identical scan settings were retrospectively included. Exams included NES (n=31), arterial (ART) (n=23), portal-venous (PVN) (n=10), and/or venous scan (VEN) (n=31). Density and area of visceral (VAT) and subcutaneous adipose tissue (SAT) were quantified semi-automatically with fixed thresholds. For conversion of values from CES into those of NES regression analyses were performed and tested. 2D- and 3D-segmentation were compared with respect to conversion accuracy (normalized deviations of converted NES values from original measurements). RESULTS: After the application of contrast medium 2D-segmented adipose tissue increased in density (max. +5.6±2.4 HU) and decreased in area (max. -10.91%) (10.47%), with few exceptions (P<0.05). This was more pronounced in later scans (VEN ≈ PVN > ART) and more marked in VAT than SAT. Density and area in CES correlated very well with NES, allowing for conversion with only small error. While converted density is slightly more precise applying 3D-segmentation, conversion error of quantity was occasionally smaller with 2D-segmentation. CONCLUSIONS: Contrast medium changes density and quantity of segmented adipose tissue in differing degrees between compartments, contrast phases and 2D- and 3D-segmentation. However, changes are fairly constant for a given compartment, contrast phase and mode of segmentation. Therefore, conversion of values into those of NES may be achieved with comparable precision for 2D- and 3D-segmentation.

Cost-Effectiveness of Tisagenlecleucel in Paediatric Acute Lymphoblastic Leukaemia (pALL) and Adult Diffuse Large B-Cell Lymphoma (DLBCL) in Switzerland.

INTRODUCTION: The purpose of the present analysis was to explore the cost-effectiveness of tisagenlecleucel in relapsed or refractory (r/r) paediatric acute lymphoblastic leukaemia (pALL) and r/r adult diffuse large B-cell lymphoma (DLBCL) in Switzerland against a range of historical standard-of-care treatments. METHODS: Two cost-utility models were constructed for the two licensed indications using similar methodologies but indication-specific data. Clinical efficacy data were based on pooled analyses of clinical trials for tisagenlecleucel (pALL: ELIANA, ENSIGN, B2101J; DLBCL: JULIET, NCT02030834) and published data for comparator treatments. Treatment effects were compared based on matching-adjusted indirect comparison (MAIC) analyses. Four clinical lymphoma and leukaemia experts provided Switzerland-specific input regarding comparators, diagnostic and therapeutic procedures, clinical evidence and costs, which were used to inform the models. The base case analysis reflected the perspective of the Swiss mandatory health insurance system. Deterministic, probabilistic and scenario analyses were carried out to explore the robustness of results. RESULTS: The base case analysis resulted in incremental costs of CHF 31,961-CHF 36,419 per quality-adjusted life year (QALY) gained for pALL across the different comparators and CHF 113,179 for DLBCL (1 CHF = 1.09 USD). Incremental costs per life-year gained ranged between CHF 33,906-CHF 97,399 across the two indications. Including productivity gains, tisagenlecleucel was shown to be dominant (more effective and less costly) over all the comparators for pALL and to result in incremental costs per life-year gained of CHF 57,324 for DLBCL. CONCLUSION: Using hypothetical willingness-to-pay thresholds of CHF 100,000-150,000 per QALY gained, the present analysis has shown tisagenlecleucel to be a cost-effective treatment option in pALL and DLBCL.

3D-segmentation and characterization of visceral and abdominal subcutaneous adipose tissue on CT: influence of contrast medium and contrast phase.

BACKGROUND: Adipose tissue as part of body composition analysis may serve as a powerful biomarker. Validation of segmented adipose tissue and correlation to clinical data has been performed on non-enhanced scans (NES). As many patients require a contrast enhanced scan (CES) for other aspects of clinical decision making, the utility of CES for body composition analysis would be most useful. Therefore, we analyzed the influence of iodinated contrast medium (ICM) and contrast phase on the characterization and segmentation of adipose tissue. METHODS: Exams of 31 patients undergoing multi-phasic CT at identical scan settings containing an NES were retrospectively included. In addition to NES, patients received an arterial (ART) (n=23), portal-venous (PVN) (n=10), and/or venous scan (VEN) (n=31) after intravenous injection of 90 mL ICM. Density and volume of adipose tissue were quantified semi-automatically with thresholds between -190 HU and -30 HU and recorded separately for visceral (VAT) and subcutaneous adipose tissue (SAT). Density and volume of total adipose tissue (TAT) were computed. For conversion of values from CES into those of NES regression analyses were performed and tested. RESULTS: Density of adipose tissue increased after application of ICM more on later scans (VEN ≈ PVN > ART) and more markedly in VAT than SAT (VAT > TAT > SAT). Except in SAT on ART, all changes were significant (P<0.001). Measured volume of adipose tissue decreased on all CES (VEN ≈ PVN > ART) (P<0.001), but only reached statistical significance for VAT and TAT (VAT > TAT) on all CES (P<0.05). Density and volume in CES correlate extremely well with NES and may be calculated from one another [root-mean-square error (RMSE): <6 HU; <0.85 dm3]. CONCLUSIONS: Density and volume of segmented adipose tissue are altered by the injection of ICM in differing degrees between compartments and contrast phases. However, as the effect of ICM is fairly constant for a given compartment and contrast phase, values may be converted into those of NES with relative precession. This conversion allows body composition analysis to be carried out also in contrast enhanced CT examinations, e.g., for risk stratification and the comparison of the obtained results to previous studies.

Myasthenia Gravis Induced by Nivolumab: A Case Report.

Nivolumab is a programmed cell death receptor (PD-1) inhibitor therapy for aggressive cancers; however, it poses a risk of immune-related adverse side effects. We present a 73-year-old male with renal cell carcinoma who developed myasthenia gravis (MG) after being treated with nivolumab, proven by acetylcholine receptor antibodies. Our patient presented with symptoms of fatigue and upper and lower extremity weakness, eventually resulting in respiratory failure as a result of MG. Nivolumab is an emerging therapy for advanced cancers but poses severe immune-related adverse events. Clinicians using PD-1 inhibitors should have a high index of suspicion of autoimmune diseases so that early discontinuation and treatment can be established to limit long-term morbidity and mortality.

Spiroindolones, a potent compound class for the treatment of malaria.

Recent reports of increased tolerance to artemisinin derivatives--the most recently adopted class of antimalarials--have prompted a need for new treatments. The spirotetrahydro-beta-carbolines, or spiroindolones, are potent drugs that kill the blood stages of Plasmodium falciparum and Plasmodium vivax clinical isolates at low nanomolar concentration. Spiroindolones rapidly inhibit protein synthesis in P. falciparum, an effect that is ablated in parasites bearing nonsynonymous mutations in the gene encoding the P-type cation-transporter ATPase4 (PfATP4). The optimized spiroindolone NITD609 shows pharmacokinetic properties compatible with once-daily oral dosing and has single-dose efficacy in a rodent malaria model.