Natural history of PF4 antibodies in vaccine-induced immune thrombocytopenia and thrombosis.

The COVID-19 pandemic has resulted in the rapid development of a range of vaccines against SARS-CoV-2. Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare but life-threatening complication of primarily adenoviral-based vaccines associated with the presence of antibodies to a PF4/polyanion neoepitope and measured by using enzyme-linked immunosorbent assays. Presented are serial anti-PF4/polyanion antibody, platelet, and D-dimer measurements in a large cohort of patients and their relation to relapse. Overall, 51% of patients using the Stago assay had persistently positive anti-PF4/polyanion levels 100 days' postdiagnosis, whereas 94% of patients monitored by using the Immucor assay remain positive. The median duration of positivity of the PF4 assay is 87 days, with 72% of patients remaining positive after a median follow-up of 105 days. The use of plasma exchange seemed to reduce anti-PF4/polyanion levels and increase platelet counts in the acute setting more rapidly than other therapies. The rate of relapse in this study was 12.6%, with all relapsed cases exhibiting persistently positive PF4 antibodies and falling platelet counts. Only one patient had extension of their thrombosis. Overall, despite the persistence of PF4 antibodies in 72% of patients, the rate of relapse was low and did not seem to result in recrudescence of the aggressive clinical picture seen at index presentation. Monitoring of these patients in the UK cohort is ongoing and will aid in definition of the natural history of this novel condition.

Presenting Symptoms in Newly Diagnosed Myeloma, Relation to Organ Damage, and Implications for Symptom-Directed Screening: A Secondary Analysis from the Tackling Early Morbidity and Mortality in Myeloma (TEAMM) Trial.

Multiple myeloma (MM) patients risk diagnostic delays and irreversible organ damage. In those with newly diagnosed myeloma, we explored the presenting symptoms to identify early signals of MM and their relationships to organ damage. The symptoms were recorded in patients' own words at diagnosis and included diagnostic time intervals. Those seen by a haematologist >6 months prior to MM diagnosis were classified as precursor disease (PD). Most (962/977) patients provided data. Back pain (38%), other pain (31%) and systemic symptoms (28%) predominated. Patients rarely complain of 'bone pain', simply 'pain'. Vertebral fractures are under-recognised as pathological and are the predominant irreversible organ damage (27% of patients), impacting the performance status (PS) and associated with back pain (odds ratio (OR) 6.14 [CI 4.47-8.44]), bone disease (OR 3.71 [CI 1.88-7.32]) and age >65 years (OR 1.58 [CI 1.15-2.17]). Renal failure is less frequent and associated with gastrointestinal symptoms (OR 2.23 [CI1.28-3.91]), age >65 years (OR 2.14 [CI1.28-3.91]) and absence of back pain (OR 0.44 [CI 0.29-0.67]). Patients with known PD (n = 149) had fewer vertebral fractures (p = 0.001), fewer adverse features (p = 0.001), less decline in PS (p = 0.001) and a lower stage (p = 0.04) than 813 with de novo MM. Our data suggest subgroups suitable for trials of 'symptom-directed' screening: those with back pain, unexplained pain, a general decline in health or low-impact vertebral compression fractures.

Morphologic predictors of a microbiological yield in patients with a tree-in-bud pattern on computed tomography.

PURPOSE: To evaluate the computed tomographic (CT) predictors of a clinically significant yield from microbiological tests in patients with a tree-in-bud pattern. MATERIALS AND METHODS: CT examinations in 53 patients (male=34; mean age=52.9 ± 17.3 y) with a tree-in-bud pattern in whom a diagnostic test (sputum analysis, bronchoalveolar lavage or nasopharyngeal aspirates) had been performed within 2 weeks were identified. The following CT patterns were independently quantified by 2 thoracic radiologists: tree-in-bud, bronchiectasis, bronchial wall thickening, consolidation, ground-glass opacification, and nodules. The presence of cavitation (in nodules and/or consolidation) was recorded. Patient charts were reviewed for the presence of a clinically significant positive microbiological result. RESULTS: A clinically significant causal organism was present in 25/53 (47%) patients. The median extent of a tree-in-bud pattern was 5 [range=1 to 16 (maximum range=0 to 18)], and cavitation was present in 14/53 (26%) patients (cavitating nodules=8, cavitation in consolidation=3, and cavitation in consolidation and nodules=3). There was no independent linkage between the extent of a tree-in-bud pattern and the identification of a clinically significant organism. The microbiological yield was significantly higher if there was coexistent cavitation in nodules or consolidation [11/14 (79%) vs. 14/39 (39%); P=0.005]. On stepwise logistic regression, the only CT predictor of a clinically significant microbiological yield was cavitation on CT (odds ratio=9.7; 95% confidence interval=1.9, 49.9; P<0.01); the extent of a tree-in-bud pattern, concurrent use of antibiotics, age, and sex were not independently linked to a significant microbiological yield. CONCLUSIONS: A specific clinically significant microbiological diagnosis was obtained in approximately 50% of patients with a tree-in-bud pattern. The microbiological yield rises strikingly when a tree-in-bud pattern coexists with cavitation (in nodules or consolidation) but is not predicted by ancillary CT signs or clinical parameters.