Tracking SARS-CoV-2 Spike Protein Mutations in the United States (January 2020—March 2021) Using a Statistical Learning Strategy

The emergence and establishment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of interest (VOIs) and variants of concern (VOCs) highlight the importance of genomic surveillance. We propose a statistical learning strategy (SLS) for identifying and spatiotemporally tracking potentially relevant Spike protein mutations. We analyzed 167,893 Spike protein sequences from coronavirus disease 2019 (COVID-19) cases in the United States (excluding 21,391 sequences from VOI/VOC strains) deposited at GISAID from 19 January 2020 to 15 March 2021. Alignment against the reference Spike protein sequence led to the identification of viral residue variants (VRVs), i.e., residues harboring a substitution compared to the reference strain. Next, generalized additive models were applied to model VRV temporal dynamics and to identify VRVs with significant and substantial dynamics (false discovery rate q-value < 0.01; maximum VRV proportion >10% on at least one day). Unsupervised learning was then applied to hierarchically organize VRVs by spatiotemporal patterns and identify VRV-haplotypes. Finally, homology modeling was performed to gain insight into the potential impact of VRVs on Spike protein structure. We identified 90 VRVs, 71 of which had not previously been observed in a VOI/VOC, and 35 of which have emerged recently and are durably present. Our analysis identified 17 VRVs ~91 days earlier than their first corresponding VOI/VOC publication. Unsupervised learning revealed eight VRV-haplotypes of four VRVs or more, suggesting two emerging strains (B1.1.222 and B.1.234). Structural modeling supported a potential functional impact of the D1118H and L452R mutations. The SLS approach equally monitors all Spike residues over time, independently of existing phylogenic classifications, and is complementary to existing genomic surveillance methods.     

Type II endoleak after endovascular abdominal aortic aneurysm repair: a conservative approach with selective intervention is safe and cost-effective

OBJECTIVES: The conservative versus therapeutic approach to type II endoleak after endovascular repair of abdominal aortic aneurysm (EVAR) has been controversial. The purpose of this study was to evaluate the safety and cost-effectiveness of the conservative approach of embolizing type II endoleak only when persistent for more than 6 months and associated with aneurysm sac growth of 5 mm or more. METHODS: Data for 486 consecutive patients who underwent EVAR were analyzed for incidence and outcome of type II endoleaks. Spiral computed tomography (CT) scans were reviewed, and patient outcome was evaluated at either office visit or telephone contact. Patients with new or late-appearing type II endoleak were evaluated with spiral CT at 6-month intervals to evaluate both persistence of the endoleak and size of the aneurysm sac. Persistent (>or=6 months) type II endoleak and aneurysm sac growth of 5 mm or greater were treated with either translumbar glue or coil embolization of the lumbar source, or transarterial coil embolization of the inferior mesenteric artery. RESULTS: Type II endoleaks were detected in 90 (18.5%) patients. With a mean follow-up of 21.7 +/- 16 months, only 35 (7.2%) patients had type II endoleak that persisted for 6 months or longer. Aneurysm sac enlargement was noted in 5 patients, representing 1% of the total series. All 5 patients underwent successful translumbar sac embolization (n = 4) or transarterial inferior mesenteric artery embolization (n = 4) at a mean follow-up of 18.2 +/- 8.0 months, with no recurrence or aneurysm sac growth. No patient with treated or untreated type II endoleak has had rupture of the aneurysm. The mean global cost for treatment of persistent type II endoleak associated with aneurysm sac growth was US dollars 6695.50 (hospital cost plus physician reimbursement). Treatment in the 30 patients with persistent type II endoleak but no aneurysm sac growth would have represented an additional cost of US dollars 200000 or more. The presence or absence of a type II endoleak did not affect survival (78% vs 73%) at 48 months. CONCLUSIONS: Selective intervention to treat type II endoleak that persists for 6 months and is associated with aneurysm enlargement seems to be both safe and cost-effective. Longer follow-up will determine whether this conservative approach to management of type II endoleak is the standard of care.     

Effects of positive and negative pressure ventilation on cerebral blood volume of newborn infants

The effects of intermittent positive airway and continuous negative extrathoracic pressure ventilation on cerebral blood volume in preterm infants were studied using near infrared spectroscopy. In 12 infants continuous negative extrathoracic pressure caused a median decrease in cerebral blood volume of 0.14ml/100ml brain (95% confidence intervals (CI) 0.035–0.280) compared with no respiratory support. Oxygenated and deoxygenated haemoglobin also decreased, implying increased venous drainage as the main effect. In 17 infants intermittent positive pressure ventilation also caused a median reduction in cerebral blood volume of 0.06 ml/100 ml brain (95% CI 0.010–0.115) compared with endotracheal positive airway pressure. Deoxygenated haemoglobin increased by 0.07 ml/100 ml brain (95% CI 0.010–0.100) while oxygenated haemoglobin decreased by O.lOml/lOOml brain (95% CI 0.005–0.175). The increase in deoxygenated haemoglobin implies decreased venous drainage and the decrease in oxygenated haemoglobin implies that other factors may also be significant. Heart rate, blood pressure and oxygen saturation were monitored continuously and remained stable.     

Tachykinin receptor (NK(1), NK(2), NK(3)) binding sites in the rat caudal brainstem following neonatal capsaicin administration

Binding of [125I]-Bolton-Hunter substance P ([125I]-BHSP), [125I]-neurokinin A and [3H]-senktide to tachykinin NK(1), NK(2) and NK(3) receptors, respectively, was examined in caudal brainstem sections of 10-week-old rats pretreated as neonates (P2) with capsaicin (50 mg/kg, s.c.) or vehicle. [125I]-BHSP binding was localised to the nucleus of the solitary tract (NTS), hypoglossal nucleus and inferior olivary complex, whereas [125I]-neurokinin A and [3H]-senktide binding were confined to the NTS. The distribution and density of binding sites were similar in vehicle- and capsaicin-pretreated rats, suggesting that sensory neuron ablation by neonatal capsaicin does not affect tachykinin receptor numbers in the rat caudal brainstem.