Severe SARS-CoV-2 Breakthrough Reinfection With Delta Variant After Recovery From Breakthrough Infection by Alpha Variant in a Fully Vaccinated Health Worker.

Background: Post infection immunity and post vaccination immunity both confer protection against COVID-19. However, there have been many whole genome sequencing proven reinfections and breakthrough infections. Both are most often mild and caused by Variants of Concern (VOC). Methods: The patient in our study underwent serial COVID-19 RT-PCR, blood tests for serology, acute phase reactants, and chest imaging as part of clinical care. We interviewed the patient for clinical history and retrieved reports and case papers. We retrieved stored RT-PCR positive samples for whole genome sequencing (WGS) of SARS-CoV-2 from the patient's breakthrough infections and the presumed index case. Findings: The patient had three RT-PCR confirmed SARS-CoV-2 infections. Two breakthrough infections occurred in quick succession with the first over 3 weeks after complete vaccination with COVISHIELD and despite post-vaccination seroconversion. The first breakthrough infection was due to the Alpha variant and the second due to the Delta variant. The Delta variant infection resulted in hypoxia, hospitalization, and illness lasting seven weeks. Serial serology, acute phase reactants, and chest imaging supported WGS in establishing distinct episodes of infection. WGS established a fully vaccinated family member as the index case. Interpretation: The patient had an Alpha variant breakthrough infection despite past infection, complete vaccination, and seroconversion. Despite boosting after this infection, the patient subsequently had a severe Delta variant breakthrough infection. This was also a WGS proven reinfection and, therefore, a case of breakthrough reinfection. The patient acquired the infection from a fully vaccinated family member.

Opportunistic diagnosis of osteoporosis, fragile bone strength and vertebral fractures from routine CT scans; a review of approved technology systems and pathways to implementation.

Osteoporosis causes bones to become weak, porous and fracture more easily. While a vertebral fracture is the archetypal fracture of osteoporosis, it is also the most difficult to diagnose clinically. Patients often suffer further spine or other fractures, deformity, height loss and pain before diagnosis. There were an estimated 520,000 fragility fractures in the United Kingdom (UK) in 2017 (costing £4.5 billion), a figure set to increase 30% by 2030. One way to improve both vertebral fracture identification and the diagnosis of osteoporosis is to assess a patient's spine or hips during routine computed tomography (CT) scans. Patients attend routine CT for diagnosis and monitoring of various medical conditions, but the skeleton can be overlooked as radiologists concentrate on the primary reason for scanning. More than half a million CT scans done each year in the National Health Service (NHS) could potentially be screened for osteoporosis (increasing 5% annually). If CT-based screening became embedded in practice, then the technique could have a positive clinical impact in the identification of fragility fracture and/or low bone density. Several companies have developed software methods to diagnose osteoporosis/fragile bone strength and/or identify vertebral fractures in CT datasets, using various methods that include image processing, computational modelling, artificial intelligence and biomechanical engineering concepts. Technology to evaluate Hounsfield units is used to calculate bone density, but not necessarily bone strength. In this rapid evidence review, we summarise the current literature underpinning approved technologies for opportunistic screening of routine CT images to identify fractures, bone density or strength information. We highlight how other new software technologies have become embedded in NHS clinical practice (having overcome barriers to implementation) and highlight how the novel osteoporosis technologies could follow suit. We define the key unanswered questions where further research is needed to enable the adoption of these technologies for maximal patient benefit.

Comprehensive multi-modality assessment of regional and global arterial structure and function in adults born preterm.

Preterm birth is associated with higher blood pressure, which could be because preterm birth alters early aortic elastin and collagen development to cause increased arterial stiffness. We measured central and conduit artery size and multiple indices of arterial stiffness to define the extent and severity of macrovascular changes in individuals born preterm. A total of 102 young adults born preterm and 102 controls who were born after an uncomplicated pregnancy underwent cardiovascular magnetic resonance on a Siemens 1.5 T scanner to measure the aortic cross-sectional area in multiple locations. Ultrasound imaging with a Philips CX50 and linear array probe was used to measure carotid and brachial artery diameters. Carotid-femoral pulse wave velocity and the augmentation index were measured by SphygmoCor, brachial-femoral pulse wave velocity by Vicorder and aortic pulse wave velocity by cardiovascular magnetic resonance. The cardio-ankle vascular index (CAVI) was used as a measurement of global stiffness, and ultrasound was used to assess peripheral vessel distensibility. Adults born preterm had 20% smaller thoracic and abdominal aortic lumens (2.19 ± 0.44 vs. 2.69 ± 0.60 cm(2), P<0.001; 1.25 ± 0.36 vs. 1.94 ± 0.45 cm(2), P<0.001, respectively) but similar carotid and brachial diameters to adults born at term. Pulse wave velocity was increased (5.82 ± 0.80 vs. 5.47 ± 0.59 m s(-1), P<0.01, 9.06 ± 1.25 vs. 8.33 ± 1.28 m s(-1), P=0.01, 5.23 ± 1.19 vs. 4.75 ± 0.91 m s(-1), P<0.01) and carotid distensibility was decreased (4.75 ± 1.31 vs. 5.60 ± 1.48 mm Hg(-1)10(3), P<0.001) in this group compared with the group born at term. However, the global and peripheral arterial stiffness measured by CAVI and brachial ultrasound did not differ (5.95 ± 0.72 vs. 5.98 ± 0.60, P=0.80 and 1.07 ± 0.48 vs. 1.19 ± 0.54 mm Hg(-1)10(3), P=0.12, respectively). Adults who are born preterm have significant differences in their aortic structure from adults born at term, but they have relatively small differences in central arterial stiffness that may be partially explained by blood pressure variations.

MLL Rearrangment and EVI1 Deletion in BCR/ABL1 Positive Chronic Myeloid Leukemia.

We present unusual cytogenetic findings in a 65-year-old female with blast phase (BC) of Philadelphia chromosome positive chronic myeloid leukemia (CML). Chromosome analysis revealed two related abnormal clones, one characterized by a t(9;22)(q34;q11.2), and the other showing a t(11;19)(q23;p13.1) in addition to the t(9;22)(q34;q11). Fluorescence in situ hybridization (FISH) testing confirmed that the t(11;19) involved the MLL gene on 11q23. High-density whole-genome SNP array analysis of leukemia cells showed a number of submicroscopic copy number abnormalities, including a deletion of the MECOM (MDS1 and EVI1 complex locus protein EVI1) gene at 3q26. Clinical course was aggressive, and the patient failed to respond to both imatinib and dasatinib despite the absence of resistance-associated mutations in the BCR/ABL1 gene. To our knowledge, the combination of a t(9;22) with t(11;19)(q23;p13.1) has only been reported in one case, while a deletion of the EVI1 gene has never been reported in CML.