Left ventricular pseudoaneurysm: an inadvertent consequence of COVID-19-a case report.

BACKGROUND: Left ventricular pseudoaneurysm (LVP) is an uncommon but serious mechanical complication of acute myocardial infarction (AMI). The immediate medical complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are well recognized, but its indirect effect on patients and healthcare systems is potentially less perceivable. CASE SUMMARY: In this report, a 72-year-old man who was anxious about attending hospital during the SARS-CoV-2 pandemic was eventually found to have a total right coronary artery occlusion after a delayed emergency department presentation. He ultimately developed severe symptomatic heart failure and cardiac magnetic resonance imaging (CMR) revealed that a large LVP with concomitant severe ischaemic mitral regurgitation had evolved from his infarct. The patient was successfully discharged home after the surgical replacement of his mitral valve and repair of his LVP. DISCUSSION: This case highlights a salient downstream effect of Coronavirus disease 2019 (COVID-19): the delay in presentation, diagnosis, and management of common treatable conditions such as AMI. It also underscores the importance of non-invasive multimodal imaging on the timely identification of the mechanical complications of AMI. In particular, CMR can play a crucial role in the characterization and management of LVP.

Hb Tacoma: G>T or G>C, and Does It Matter?

Hb Tacoma [ß30(B12)Arg→Ser] is a missense variant that is caused by either an AGG>AGT or AGG>AGC substitution at codon 30 of the HBB gene. Currently, the latter is classified as a rare cause of ß0-thalassemia (ß0-thal). We propose that HBB: c.93G>C has been incorrectly assigned as ß0-thal and discuss whether HBB: c.93G>T or HBB: c.93G>C should be classified as ß+-thal instead, or as ß-globin variants without thalassemic effect. We present several subjects who are heterozygous for Hb Tacoma, one with HBB: c.93G>T and two with HBB: c.93G>C, to support our conclusions.

Hb Waikato [α127(H10)Lys→Gln; HBA1: c.382A>C]: A Novel High Oxygen Affinity Variant.

We report the identification of a novel, high oxygen affinity hemoglobin (Hb) variant [α127(H10)Lys→Gln; HBA1: c.382A>C]. The variant was detected in an adolescent male (proband) of Syrian descent by cation exchange high performance liquid chromatography (HPLC), during Hb A1c analysis. A complete blood count (CBC) showed elevated red blood cells (RBCs) (6.08 × 1012/L), Hb (16.1 g/dL) and packed cell volume (PCV) (0.48 L/L). Capillary electrophoresis (CE) revealed the variant was more negatively charged and represented 18.2% of total Hb. Isopropanol stability was normal. Cyanosis in the subject prompted investigation of oxygen affinity, with a reduced p50 of 20.8 mm Hg and a left shifted oxygen dissociation curve demonstrating increased oxygen affinity. We propose the novel variant be named Hb Waikato, which reflects the Hospital Laboratory where the variant was discovered and region where the proband was born and herein describe characterization.

Novel α0-Thalassemia Deletion Identified in an Indian Infant with Hb H Disease.

We report the identification of a large deletion of the α-globin gene cluster, which removed both HBA2 and HBA1 and included the region from HBZ to HBQ1 on chromosome 16 (16p13.3). The α0-thalassemia (α0-thal) deletion was discovered in an Indian family residing in New Zealand. The proband was a 3-month-old female, who presented with a Hb H disease of unknown molecular origin. Routine hematology showed marked hypochromic microcytic anemia, with numerous Hb H inclusion bodies. In the absence of iron deficiency, there was a strong clinical suspicion of α-thal. On initial screening using a multiplex gap polymerase chain reaction (gap-PCR), only the common rightward deletion (-α3.7) was detected. Investigation of the proband's mother and father revealed the mother was heterozygous for the -α3.7 deletion, while none of the seven most common pathogenic α-thal deletions were detected in the father. Multiplex ligation-dependent probe amplification (MLPA) was employed to detect the presence of a novel α0-thal deletion in both the proband and her father. For the proband, the α0-thal deletion in combination with the -α3.7 deletion, eliminated three copies of HBA consistent with a clinical diagnosis of Hb H disease.

An intact C-terminal end of albumin is required for its long half-life in humans.

Albumin has an average plasma half-life of three weeks and is thus an attractive carrier to improve the pharmacokinetics of fused therapeutics. The half-life is regulated by FcRn, a cellular receptor that protects against intracellular degradation. To tailor-design the therapeutic use of albumin, it is crucial to understand how structural alterations in albumin affect FcRn binding and transport properties. In the blood, the last C-terminal residue (L585) of albumin may be enzymatically cleaved. Here we demonstrate that removal of the L585 residue causes structural stabilization in regions of the principal FcRn binding domain and reduces receptor binding. In line with this, a short half-life of only 3.5 days was measured for cleaved albumin lacking L585 in a patient with acute pancreatitis. Thus, we reveal the structural requirement of an intact C-terminal end of albumin for a long plasma half-life, which has implications for design of albumin-based therapeutics.

Small mammal responses to long-term large-scale woodland creation: the influence of local and landscape-level attributes.

Habitat loss and fragmentation greatly affect biological diversity. Actions to counteract their negative effects include increasing the quality, amount and connectivity of seminatural habitats at the landscape scale. However, much of the scientific evidence underpinning landscape restoration comes from studies of habitat loss and fragmentation, and it is unclear whether the ecological principles derived from habitat removal investigations are applicable to habitat creation. In addition, the relative importance of local- (e.g., improving habitat quality) vs. landscape-level (e.g., increasing habitat connectivity) actions to restore species is largely unknown, partly because studying species responses over sufficiently large spatial and temporal scales is challenging. We studied small mammal responses to large-scale woodland creation spanning 150 yr, and assessed the influence of local- and landscape-level characteristics on three small mammal species of varying woodland affinity. Woodland specialists, generalists, and grassland specialists were present in woodlands across a range of ages from 10 to 160 yr, demonstrating that these species can quickly colonize newly created woodlands. However, we found evidence that woodlands become gradually better over time for some species. The responses of individual species corresponded to their habitat specificity. A grassland specialist (Microtus agrestis) was influenced only by landscape attributes; a woodland generalist (Apodemus sylvaticus) and specialist (Myodes glareolus) were primarily influenced by local habitat attributes, and partially by landscape characteristics. At the local scale, high structural heterogeneity, large amounts of deadwood, and a relatively open understory positively influenced woodland species (both generalists and specialists); livestock grazing had strong negative effects on woodland species abundance. Actions to enhance habitat quality at the patch scale focusing on these attributes would benefit these species. Woodland creation in agricultural landscapes is also likely to benefit larger mammals and birds of prey feeding on small mammals and increase ecosystem processes such as seed dispersal.

Standardized traction versus side-bending radiographs in adolescent idiopathic scoliosis: a preliminary study.

The aim of this study was to develop a new type of preoperative flexibility test for adolescent idiopathic scoliosis. The objective was to develop a test that was standardized and allow for the measurement of in-vivo forces required for curve correction. It was undertaken to compare the results of this new test with side-bending radiographs. Various preoperative radiographic techniques have been used to assess flexibility in patients awaiting scoliosis correction surgery. The major limitation of these investigations is a lack of standardization. The side-bending radiograph is the current gold standard, against which this new test was compared. A prospective clinical study was conducted. An axial traction force of 1.5 times body weight was applied through the spine of patients using a traction jig. Posteroanterior, side-bending and traction radiographs were taken. Cobb angle and apical vertebra axial rotation measurements were obtained. Flexibility indices in the coronal and axial planes were calculated. Cobb angle reduction and axial derotation were compared between the two methods. A total of 15 (12 female and three male) patients, with a mean age of 15.1 years, were assessed. The mean force imparted on traction films was 800 N. The major curve Cobb angle measurements were 60.4° on standing posteroanterior radiograph, 52.7° on side-bend film and 44.5° on traction at 1.5 times body weight. The corresponding apical vertebrae axial rotations were 23.9°, 22.2° and 16.5°, respectively. The mean Cobb angle reduction was 15.9 for traction and 7.7 for side-bend radiographs (P<0.0001). The mean apical vertebra derotation was 7.4 for traction and 1.7° for side-bend radiographs (P=0.0083). The mean flexibility index in the coronal plane was 0.479. The mean flexibility index in the axial plane was 0.240. Our novel method of traction radiographs at 1.5 times body weight is a safe and reproducible method of assessing curve flexibility in patients with scoliosis. This method achieves a larger Cobb angle and axial derotation when compared with side-bending radiographs.

Conjugation of urate-derived electrophiles to proteins during normal metabolism and inflammation.

Urate is often viewed as an antioxidant. Here, we present an alternative perspective by showing that, when oxidized, urate propagates oxidative stress. Oxidation converts urate to the urate radical and the electrophilic products dehydrourate, 5-hydroxyisourate, and urate hydroperoxide, which eventually break down to allantoin. We investigated whether urate-derived electrophiles are intercepted by nucleophilic amino acid residues to form stable adducts on proteins. When urate was oxidized in the presence of various peptides and proteins, two adducts derived from urate (Mr 167 Da) were detected and had mass additions of 140 and 166 Da, occurring mainly on lysine residues and N-terminal amines. The adduct with a 140-Da mass addition was detected more frequently and was stable. Dehydrourate (Mr 166 Da) also formed transient adducts with cysteine residues. Urate-derived adducts were detected on human serum albumin in plasma of healthy donors. Basal adduct levels increased when neutrophils were added to plasma and stimulated, and relied on the NADPH oxidase, myeloperoxidase, hydrogen peroxide, and superoxide. Adducts of oxidized urate on serum albumin were elevated in plasma and synovial fluid from individuals with gout and rheumatoid arthritis. We propose that rather than acting as an antioxidant, urate's conversion to electrophiles contributes to oxidative stress. The addition of urate-derived electrophiles to nucleophilic amino acid residues, a process we call oxidative uratylation, will leave a footprint on proteins that could alter their function when critical sites are modified.

Acetabular Revision Using Trabecular Metal Augments for Paprosky Type 3 Defects.

BACKGROUND: Trabecular Metal (TM) augments are one option when reconstructing bone loss during acetabular side revision surgery. METHODS: We studied 38 consecutive patients with Paprosky type 3 defects that were revised using a TM shell and one or more augments over a 6-year period. There were 29 Paprosky type 3A defects and 9 Paprosky type 3B defects. The mean age of the patients at the time of surgery was 68.2 years (range 48-84). The mean length of follow-up was 36 months (range 18-74). RESULTS: The mean preoperative short form 12 health survey improved from 27.7 before operation to 30.1 at the time of final follow-up (P = .001). The mean Western Ontario and McMaster Universities Osteoarthritis Index score improved from 53 preoperatively to a mean of 78.8 at final follow-up (P < .0001). There was evidence of radiographic loosening in 7 of the cup-augment constructs. One patient developed a deep infection requiring re-revision. Two patients required revision for aseptic loosening. CONCLUSION: The use of TM in complex acetabular reconstruction is associated with good outcome in the short to medium term.

Hb Amsterdam-A1 [α32(B13)Met→Ile; HBA1: c.99G>A]: A Hyperunstable Variant Due to a New Mutation on the α1 Gene.

Patients with hyperunstable α chain variants usually present with a thalassemic, rather than hemolytic, phenotype. Electrophoretic, ion exchange and reverse phase separations usually fail to detect the variant and when DNA sequencing identifies a 'silent' substitution it is usually presumed to be hyperunstable. We report the identification of such a variant, α32(B13)Met→Ile; HBA1: c.99G>A, arising from a new mutation on the α1 gene. The hemoglobin (Hb) was unequivocally detected by the isopropanol stability test and confirmed as hyperunstable by mass spectrometry (MS) of the precipitate and lysate, which showed proportions of 55% and 2.5% of α chains, respectively. The instability appears to be driven by perturbation of globin-heme, and possibly α1ß1 subunit, interactions.

The impact of trabecular metal on hip centre of rotation in revision and complex primary hip arthroplasty, a radiological review.

INTRODUCTION: Total hip arthroplasty (THA) is a very successful procedure. Revision THA is becoming increasingly common. Recent developments to improve outcomes include the development of large trabecular metal (TM) acetabular cups and augments. There is a paucity of data on the benefit of these new techniques. METHODS: A single-centre retrospective review consisting of a radiological review of post-op revision THA anteroposterior pelvis. Data collection was performed using the Irish National Orthopaedic Register (INOR) and from a previous project. We used a technique developed by Fessy et al in 1999 to measure the centre of rotation (COR) of the hip. We then compared our study to that of a study measuring the COR of healthy native hips. RESULTS: 127 revision THA analysed. Native COR calculated by Fessy et al showed a mean horizontal (x) axis 33.6 mm (standard deviation [SD] 5.74) and a vertical (y) axis 16.4 mm (SD 4.67). Non-TM revisions showed a mean x axis of 29 mm (SD 3.9) and y axis 17.9 (SD 5.9). TM Augments had a mean x axis 29.2 mm (SD 7.9) and y axis of 21.5 (SD 8.4). TM Cups alone had a mean x axis 27 mm (SD 6.9) and y axis 22 mm (SD 10.18). CONCLUSIONS: COR of TM implants showed considerable deviation from the norm. Non-TM implants showed a COR within acceptable physiological range. TM components consistently failed to restore a natural COR in our cohort. The implications of this remain uncertain but must be considered in any decision to use TM.

Direct analysis of VLDL by TOF-MS allows rapid definition of Apo E genotypes and facilitates characterisation of post translational changes.

BACKGROUND: Apolipoprotein E (Apo E) is a glycoprotein which acts as a ligand facilitating the uptake of lipids. Three common isoforms of Apo E are recognised, E2, E3 and E4. E2 and E4 are associated with altered lipid metabolism and increased cardiovascular risk. We report a novel variant of Apo E (c.382G>A) predicting 110Asp→Asn identified by genotyping, we were prompted to investigate this further as the amino acid substitution produced a prospective N-glycosylation site in this novel variant. METHODS: We present a new rapid approach to genotyping Apo E performed by electrospray TOF-MS, on the same sample analysed by ultracentrifugation. The analysis can be performed in <10min and requires minimal sample volume. Control samples were used to verify the analysis. RESULTS: Spectra showed the expected mass for the E3 isoform at 34,237Da, E2 and E4 isoforms were identifiable by peaks at -53Da and +53Da respectively. Post translational glycosylation of the protein can also be identified. The novel isoform had a mass of 34,237Da without evidence of N-glycosylation. No significant effect on lipid metabolism was identified. CONCLUSION: The electrospray TOF-MS approach potentially provides a rapid alternative method for genotyping Apo E and for the investigation of novel isoforms.