Incidence, risk factors, and outcomes of venous and arterial thromboembolism in immune checkpoint inhibitor therapy.

The risk of venous thromboembolism (VTE) and arterial thromboembolism (ATE) associated with immune checkpoint inhibitors is currently unclear. Our aim was to quantify the risk of VTE/ATE in patients with cancer treated with immune checkpoint inhibitors, explore clinical impact, and investigate potential clinical risk factors. Patients treated with immune checkpoint inhibitors at the Medical University of Vienna from 2015 to 2018 were identified using in-house pharmacy records (n = 672; most frequent entities: 30.4% melanoma, 24.1% non-small cell lung cancer; 86% stage IV disease). A retrospective chart review was performed to screen for VTE and/or ATE. Cumulative incidences and between-group differences were estimated in competing-risk analysis. The impact of VTE/ATE on mortality was studied by multistate modelling. Over a median follow-up of 8.5 months, 47 VTEs and 9 ATEs were observed. Cumulative incidences of VTE and ATE were 12.9% (95% confidence interval [CI], 8.2-18.5) and 1.8% (95% CI, 0.7-3.6). Occurrence of VTE was associated with increased mortality (transition hazard ratio, 3.09; 95% CI, 2.07-4.60). History of VTE predicted VTE occurrence (subdistribution hazard ratio [SHR], 3.69; 95% CI, 2.00-6.81), and distant metastasis was nonsignificantly associated with VTE risk (SHR, 1.71; 95% CI, 0.62-4.73). No association of VTE with Eastern Cooperative Oncology Group performance status, Charlson comorbidity index, or Khorana score was observed, and rates of VTE were comparable between tumor types and checkpoint-inhibitory agents. In conclusion, patients with cancer under immune checkpoint inhibitor therapy are at high risk of thromboembolism, especially VTE. Furthermore, VTE occurrence was associated with increased mortality.

Obesity due to melanocortin 4 receptor (MC4R) deficiency is associated with delayed gastric emptying.

OBJECTIVE: People who are severely obese due to melanocortin-4 receptor (MC4R) deficiency experience hyperphagia and impaired fullness after a meal (satiety). Meal-induced satiety is influenced by hormones, such as peptide-YY (PYY), which are released by enteroendocrine cells upon nutrient delivery to the small intestine. DESIGN: We investigated whether gastric emptying and PYY levels are altered in MC4R deficiency. METHODS: Gastric emptying was measured with a gastric scintigraphy protocol using technetium-99m (99 Tcm )-Tin Colloid for 3.5 h in individuals with loss of function MC4R variants and a control group of similar age and weight. In a separate study, we measured plasma PYY levels before and at multiple time points after three standardised meals given to individuals with MC4R deficiency and controls. Fasting PYY (basal secretion) and postprandial PYY levels were measured and the area under the curve and inter-meal peak were calculated. RESULTS: We found that gastric emptying time was significantly delayed and percentage meal retention increased in individuals with MC4R deficiency compared to obese controls. In addition, fasting and mean PYY secretion throughout the day were decreased in MC4R deficiency, whereas postprandial PYY secretion was unaltered. CONCLUSION: Delayed gastric emptying and reduced basal PYY secretion may contribute to impaired satiety in people with obesity due to MC4R deficiency.

Cranial Nerve Enhancement in Multiple Sclerosis Is Associated With Younger Age at Onset and More Severe Disease.

Background: The overall frequency of cranial nerve pathology, including cranial nerves other than the trigeminal nerve, as well as its relation to brainstem lesion formation on magnetic resonance imaging (MRI) and clinical correlates in multiple sclerosis (MS) is unknown. Objective: We aimed to determine the frequency of cranial nerve enhancement on MRI, and its association with brainstem lesion formation and clinical outcomes. Methods: We retrospectively analyzed, in 183 patients, (RRMS: 156, SPMS: 15, PPMS: 6, CIS: 6) 651 MRIs (76.5% on the identical scanner Siemens Trio Tim, 3T with identical MRI protocols). Frequencies of cranial nerve enhancement on post contrast T1-weighted MRIs were compared to lesion counts and the MS-severity-score. Results: Cranial nerve enhancement was present in 8.2% of the analyzed MS patients (oculomotor-nerve: 1.1%, trigeminal-nerve: 2.7%, abducens-nerve: 2.2%, facial-/vestibulocochlear nerve: 1.6%, vagal-nerve: 0.5%). Of those, 13% suffered from repeated episodes and 27% exhibited a cranial nerve enhancement duration of >12 months. Age at MS onset was lower in patients with cranial nerve enhancement, 23 vs. 28 years, p = 0.049. The MS-severity-score, 5.15 vs. 0.88 (p = 0.019), the T2 brainstem-, 1 vs. 0 (p = 0.041), and the total intracranial contrast-enhancing lesion counts, 2 vs. 0 (p = 0.000), were higher in patients with cranial nerve enhancement, compared to age-, disease duration-, and gender- matched MS patients. Conclusions: Cranial nerve enhancement, present in 8.2% of our patients, was associated with a younger age at MS onset, brainstem lesions, and a more severe disease course.

Improved visualization of perfusion defects by respiratory-gated SPECT: a phantom simulation study.

OBJECTIVES: Single-photon emission computed tomography ventilation/perfusion (SPECT V/Q) imaging is recommended both by the Society of Nuclear Medicine and by the European Association of Nuclear Medicine for the diagnosis of pulmonary embolism. However, respiratory motion produces image blurring and degradation of detail in the lungs. We have investigated respiratory gating of SPECT images, correcting for motion to reduce blur and improve image definition. MATERIALS AND METHODS: Wedge-shaped defects of different sizes ranging from 15 to 4 mm were fixed in the lung cavities of an anthropomorphic lung phantom to simulate perfusion defects. Gated and nongated SPECT images were obtained using a double-headed SPECT system. Three-dimensional movement was introduced using a purpose-built moving platform with two motion frequencies of 10 and 20 cycles/min. Motion was tracked with a respiratory-gating system. Gated SPECT data were acquired in 16 discrete data bins in synchronization with the breathing cycle. The images were reconstructed using ordered-subset expectation maximization algorithms and corrected for rigid motion. Contrast and contrast-to-noise ratios (CNRs) were measured to quantify any improvement in the gated motion-corrected images. Visualization of defects in the reconstructed images was performed by seven observers and analyzed using alternative free-response receiver operating characteristic analysis. RESULTS: Assessment of gated and nongated SPECT phantom images demonstrated that motion adversely affected the detectability of defects. Quantification of data demonstrated that, in the controlled simulation, image quality, defect definition, observer confidence, contrast, and CNR were increased after applying motion correction. Improvement in CNRs was found to be significant using alternative free-response receiver operating characteristic analysis (P=0.0002). CONCLUSION: Respiratory-gated motion-corrected SPECT images enhanced the visualization of defects compared with matched moving/nongated images in a realistic moving phantom. This approach may be particularly valuable for SPECT V/Q imaging and may improve the diagnosis of pulmonary embolism.