Bayesian Molecular Dating Analyses Combined with Mutational Profiling Suggest an Independent Origin and Evolution of SARS-CoV-2 Omicron BA.1 and BA.2 Sub-Lineages

The ongoing evolution of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has resulted in the recent emergence of a highly divergent variant of concern (VOC) defined as Omicron or B.1.1.529. This VOC is of particular concern because it has the potential to evade most therapeutic antibodies and has undergone a sustained genetic evolution, resulting in the emergence of five distinct sub-lineages. However, the evolutionary dynamics of the initially identified Omicron BA.1 and BA.2 sub-lineages remain poorly understood. Herein, we combined Bayesian phylogenetic analysis, mutational profiling, and selection pressure analysis to track the virus’s genetic changes that drive the early evolutionary dynamics of the Omicron. Based on the Omicron dataset chosen for the improved temporal signals and sampled globally between November 2021 and January 2022, the most recent common ancestor (tMRCA) and substitution rates for BA.1 were estimated to be that of 18 September 2021 (95% highest posterior density (HPD), 4 August–22 October 2021) and 1.435 × 10⁻³ (95% HPD  =  1.021 × 10⁻³ − 1.869 × 10⁻³) substitution/site/year, respectively, whereas 3 November 2021 (95% highest posterior density (HPD) 26 September–28 November 2021) and 1.074 × 10⁻³ (95% HPD  =  6.444 × 10⁻⁴ − 1.586 × 10⁻³) substitution/site/year were estimated for the BA.2 sub-lineage. The findings of this study suggest that the Omicron BA.1 and BA.2 sub-lineages originated independently and evolved over time. Furthermore, we identified multiple sites in the spike protein undergoing continued diversifying selection that may alter the neutralization profile of BA.1. This study sheds light on the ongoing global genomic surveillance and Bayesian molecular dating analyses to better understand the evolutionary dynamics of the virus and, as a result, mitigate the impact of emerging variants on public health.     

Long-term real-world outcomes in retinal vein occlusions: How close are we to the trials?

Purpose:To assess and analyze the visual outcomes of patients with retinal vein occlusions in a real-world setting with a long-term follow-up of more than 5 years.Methods:Retrospective analysis of 56 patients having retinal vein occlusions from a tertiary eye center, with a mean follow-up of 7 years was performed. Primary outcome measures were mean change in best-corrected visual acuity (BCVA) from baseline at 6 months, 1 year, 2 years, 3 years, and final visit (≥5 years), proportion of patients having BCVA better than 20/40 and worse than 20/200, and mean number of injections. Secondary outcome measures were change in central macular thickness (CMT), development of subsequent retinal vein occlusion (RVO) in same eye or the other eye, and development of neovascular complications.Results:The mean change in letter score was + 11.84 in branch RVO (BRVO), +7.14 in non-ischemic central RVO (CRVO), and −9.5 in ischemic CRVO at 1 year, which changed to + 8.57, −5 and − 24, respectively, at the end of follow-up. CMT had improved from 506 ± 98.8 µm, 576.44 ± 149 µm, and 618 ± 178.27 µm, respectively, at baseline to 267 ± 94 µm, 345.20 ± 122.61 µm, and 265.50 ± 107.75 µm, respectively, in BRVO, non-ischemic, and ischemic hemi RVO (HRVO)/CRVO groups. The total mean number of injections given in BRVO, non-ischemic CRVO, and ischemic CRVO groups were 4.6, 6.6, and 4.1, respectively. None of the patients with BRVO developed neovascular glaucoma (NVG). Non-ischemic to ischemic HRVO/CRVO conversion was noted in 4/11 eyes at a mean duration of 12.6 months. NVG was noted in 7/9 eyes (77.8%) in initial ischemic CRVO/HRVO group and 3/4 (75%) converted eyes.Conclusion:Patients with BRVO have good visual outcomes with anti-VEGF, while in CRVO results may vary considerably owing to patient compliance and treatment burden on long-term follow-up in a real-world setting.     

Quantifying the Changes in the Tumour Vascular Micro-environment in Spinal Metastases Treated with Stereotactic Body Radiotherapy - A Single Arm Prospective Study

BackgroundThe primary objective was to quantify changes in vascular micro-environment in spinal metastases (SM) patients treated with stereotactic body radiotherapy (SBRT) with multi-parametric dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI). The secondary objective was to study plasma biomarkers related to endothelial apoptosis.Patients and methodsPatients were imaged with DCE-MRI at baseline/1-week/12-weeks post-SBRT. Metrics including normalised time-dependent leakage (Ktrans), permeability surface product (PS), fractional plasma volume (Vp), extracellular volume (Ve) and perfusion (F) were estimated using distributed parameter model. Serum acid sphingomyelinase (ASM) and sphingosine-1-phosphate (S1P) were quantified using ELISA. Clinical outcomes including physician-scored and patient-reported toxicity were collected.ResultsTwelve patients (with varying primary histology) were recruited, of whom 10 underwent SBRT. Nine patients (with 10 lesions) completed all 3 imaging assessment timepoints. One patient died due to pneumonia (unrelated) before follow-up scans were performed. Median SBRT dose was 27 Gy (range: 24–27) over 3 fractions (range: 2–3). Median follow-up for alive patients was 42-months (range: 22.3–54.3), with local control rate of 90% and one grade 2 or higher toxicity (vertebral compression fracture). In general, we found an overall trend of reduction at 12-weeks in all parameters (Ktrans/PS/Vp/Ve/F). Ktrans and PS showed a reduction as early as 1-week. Ve/Vp/F exhibited a slight rise 1-week post-SBRT before reducing below the baseline value. There were no significant changes, post-SBRT, in plasma biomarkers (ASM/S1P).ConclusionsTumour vascular micro-environment (measured by various metrics) showed a general trend towards downregulation post-SBRT. It is likely that vascular-mediated cell killing contributes to excellent local control rates seen with SBRT. Future studies should evaluate the effect of SBRT on primary-specific spinal metastases (e.g., renal cell carcinoma).Key words: spine metastases, stereotactic body radiotherapy, DCE-MRI, endothelial apoptosis     

Retinal detachment in eyes treated with Aurolab aqueous drainage implant for refractory glaucoma - Incidence and outcomes

Purpose:To analyze the incidence of rhegmatogenous retinal detachment (RRD) in patients who have undergone prior Aurolab aqueous drainage implant (AADI) surgery and report outcomes in terms of anatomic, visual acuity, and intraocular pressure (IOP) findings.Methods:Case records of all patients who underwent RRD repair after AADI surgery from 2013 to 2019 were retrospectively analyzed. Data collected included patient demographics, ocular examination findings at all visits including IOP and best-corrected visual acuity (BCVA) and clinical findings related to RRD both at baseline and postoperatively.Results:Ten eyes of nine patients were included in study. The mean age of patients was 28.2 years (median: 15 years, range: 6–83 years). Mean duration between AADI and RRD was 14 months (median 2.5 months; range 2 days-72 months). All eyes underwent pars plana vitrectomy with silicon oil injection. The preoperative LogMAR BCVA (logarithm of the minimum angle of resolution) was 2.52 ± 0.15 which improved to 2.29 ± 0.58 at final follow-up; however, only one eye had vision ≥ 20/400 largely due to recurrent RRD and advanced glaucomatous disc damage. Postoperatively retina was attached in 6 eyes (60%) and IOP was ≤ 21 mmHg in 5 out of 6 eyes with anatomic successConclusion:The incidence of RRD following AADI was found to be 0.86% in our study. Pars plana vitrectomy (PPV) with silicon oil tamponade was the preferred approach in the management of these eyes with IOP being well controlled post PPV. However, visual acuity outcomes were largely unsatisfactory due to recurrent RRD and preexisting advanced glaucoma.     

Age at menopause in India: A systematic review

Background and aimsMenopause is a physiological process in nature and hence, variations in the age of menopause are not expected. Hence, the study was conducted with an objective to calculate the reliable estimates of age at menopause for India, and understand the differentials in women’s age at menopause throughout the country.MethodsA total of 202 studies of age at menopause, covering the period 2009–2020, were accessed from PubMed database and Google. Of these only ten studies met the selection criteria for this paper, which is that the data for these studies must be collected from house-to-house surveys.ResultsThe average age at menopause in India, with minimal publication bias, is 46.6 years (95% CI: 44.83, 48.44). In one study slightly above 1.96 Standard Deviation, was observed, as ascertained by Funnel Plot and Egger’s test. The mean age ranged from a minimum of 44.69 years (95% CI: 35.01, 54.37) to a maximum of 48.95 (95% CI: 42.29, 55.61) years. Furthermore, the age at menopause did not exhibit any significant variation by age at menarche, although the association was positive.ConclusionsThe age at menopause showed positive association with age at menarche. In India, during the period 2009–2020, it was 46.6 years, which significantly lower than the age in some developed countries. The differences may be methodological since no information was found regarding the distribution of age at menopause in the studies that were considered for meta-analysis.     

☆Comparison of transcutaneous laryngeal ultrasound with video laryngoscope for assessing the vocal cord mobility in patients undergoing thyroid surgery

ObjectiveWe evaluated the accuracy and feasibility of transcutaneous laryngeal ultrasonography as an alternative to videolaryngoscopy for assessing vocal cord mobility to rule out recurrent laryngeal nerve injury following thyroidectomy.MethodsForty-five adult patients scheduled to undergo elective thyroidectomy under general anesthesia were included. Preoperatively, indirect laryngoscopy and transcutaneous laryngeal ultrasonography was done for assessing vocal cord mobility. Intraoperatively, following induction, patients were intubated using videolaryngoscope. On completion of the surgical procedure, one anesthetist performed videolaryngoscopy so as to record vocal cord mobility while the patients were being extubated in deep plane of anesthesia. Simultaneously another anesthesiologist performed transcutaneous laryngeal ultrasonography.Vocal cord mobility, changes in hemodynamics and total time duration for the two procedures was recorded. Indirect laryngoscopic assessment and flexible fiberoptic laryngoscopy was done on postoperative day 1 and 7 respectively.ResultsPostoperative videolaryngoscopy picked up bilaterally mobile vocal cords in 88.8% cases. Transcutaneous laryngeal ultrasonography could correctly identify 39(86.6%) of these patients, with 1(2.5%) patient being misdiagnosed as having bilaterally immobile vocal cords. Further, videolaryngoscopy identified 5 patients of vocal cord palsy, of which transcutaneous laryngeal ultrasonography correctly identified 3 (60%) patients. Hence, in comparison to videolaryngoscopy, the sensitivity, specificity, positive predictive value, and negative predictive value of transcutaneous laryngeal ultrasonography for assessment of vocal cords was 75%, 95.1%, 60%, and 97.5% respectively.ConclusionIn patients undergoing thyroidectomy, transcutaneous laryngeal ultrasonography can serve as a non-invasive, bedside screening tool for assessing vocal cord palsy postoperatively.