HLA‐A SNPs and amino acid variants are associated with nasopharyngeal carcinoma in Malaysian Chinese

Nasopharyngeal carcinoma (NPC) arises from the mucosal epithelium of the nasopharynx and is constantly associated with Epstein–Barr virus type 1 (EBV‐1) infection. We carried out a genome‐wide association study (GWAS) of 575,247 autosomal SNPs in 184 NPC patients and 236 healthy controls of Malaysian Chinese ethnicity. Potential association signals were replicated in a separate cohort of 260 NPC patients and 245 healthy controls. We confirmed the association of HLA‐A to NPC with the strongest signal detected in rs3869062 (p = 1.73 × 10^?9). HLA‐A fine mapping revealed associations in the amino acid variants as well as its corresponding SNPs in the antigen peptide binding groove (p_{HLA‐A‐aa‐site‐99} = 3.79 × 10^?8, p_rs1136697 = 3.79 × 10^?8) and T‐cell receptor binding site (p_{HLA‐A‐aa‐site‐145} = 1.41 × 10^?4, p_rs1059520 = 1.41 × 10^?4) of the HLA‐A. We also detected strong association signals in the 5′‐UTR region with predicted active promoter states (p_rs41545520 = 7.91 × 10^?8). SNP rs41545520 is a potential binding site for repressor ATF3, with increased binding affinity for rs41545520‐G correlated with reduced HLA‐A expression. Multivariate logistic regression diminished the effects of HLA‐A amino acid variants and SNPs, indicating a correlation with the effects of HLA‐A*11:01, and to a lesser extent HLA‐A*02:07. We report the strong genetic influence of HLA‐A on NPC susceptibility in the Malaysian Chinese.     

SARS-CoV-2 Genetic Diversity and Lineage Dynamics in Egypt during the First 18 Months of the Pandemic

COVID-19 was first diagnosed in Egypt on 14 February 2020. By the end of November 2021, over 333,840 cases and 18,832 deaths had been reported. As part of the national genomic surveillance, 1027 SARS-CoV-2 near whole-genomes were generated and published by the end of July 2021. Here we describe the genomic epidemiology of SARS-CoV-2 in Egypt over this period using a subset of 976 high-quality Egyptian genomes analyzed together with a representative set of global sequences within a phylogenetic framework. A single lineage, C.36, introduced early in the pandemic was responsible for most of the cases in Egypt. Furthermore, to remain dominant in the face of mounting immunity from previous infections and vaccinations, this lineage acquired several mutations known to confer an adaptive advantage. These results highlight the value of continuous genomic surveillance in regions where VOCs are not predominant and the need for enforcement of public health measures to prevent expansion of the existing lineages.     

Endocyclophotocoagulation combined with phacoemulsification in surgically naive primary open-angle glaucoma: three-year results

ObjectiveTo assess the safety and efficacy of endocyclophotocoagulation with phacoemulsification (phaco-ECP) in surgically naive, primary open-angle glaucoma (POAG).MethodsA retrospective case series of patients undergoing phaco-ECP between 2007 and 2017 at a single centre in London, UK. The primary outcome was intraocular pressure (IOP). Secondary outcomes were visual acuity, visual field global indices, topical medications and surgical complications. Failure criteria were: (1) IOP > 21 mmHg or <20% reduction at two consecutive visits, (2) IOP <5 mmHg and (3) further IOP-lowering surgery.ResultsEighty-three eyes from 83 patients were eligible. Pre-operatively, mean IOP (±SD) was 18.4 ± 5.2 mmHg. The mean number of topical agents (±SD) was 2.7 ± 0.9. Mean IOP (±SD) significantly reduced to 14.3 ± 4.7 at 1 year, 14.1 ± 4.0 at 2 years and 13.6 ± 3.7 at 3 years (p < 0.0001). Topical medications were significantly reduced to 1.3 ± 1.2 at 1 year, 1.7 ± 1.2 at 2 years and 1.8 ± 1.3 at 3 years (p < 0.0001). Annual IOP ‘survival’ was 70%, 54% and 45% at year 1, 2 and 3, respectively. Complications included uveitis (6%), macular oedema (2%), IOP spikes (1%) and corneal decompensation (1%) with no episodes of hypotony or retinal detachment. One patient underwent filtration surgery within 3 years (1%).ConclusionPhaco-ECP facilitates significant IOP lowering and reduction of medication burden in surgically naive POAG requiring cataract extraction. The procedure is relatively safe and without the use of implants and their associated risks.Subject terms: Optic nerve diseases, Surgery     

Visually significant opacification of hydrophilic acrylic intraocular lenses--a clinico-pathological analysis

PURPOSE: To describe the clinic-pathological analysis of the visually significant opacification of the Cirrus International Hydroflex foldable hydrophilic acrylic intraocular lens (IOL) (model SC600-2, Medical Developmental Research Inc., Clearwater, Florida) and to highlight that this IOL is the same model as the Acryflex SC600-2 IOL, by the same manufacturer. METHODS: Retrospective review of five eyes of four patients with opacification of their Cirrus International Hydroflex foldable hydrophilic acrylic IOLs (model SC600-2) after uncomplicated phacoemulsification and IOL implantation. Two IOLs were explanted from two patients 14 to 24 months after initial implantation. Each explanted lens was divided into equal halves, one half for scanning electron microscopy (SEM) study and the other half for transmission electron microscopy (TEM) examination. SEM and TEM samples were also subjected to energy dispersive X-ray analysis (EDX). RESULTS: The IOL opacification was detected 14 to 24 months after uncomplicated phacoemulsification and IOL implantation. EDX analysis showed that the crystals contained calcium and phosphorus, presumably calcium phosphate. CONCLUSIONS: The Cirrus International Hydroflex foldable hydrophilic acrylic IOL (model SC600-2) is associated with opacification, that appeared worse centrally than peripherally. This is the same model as the Acryflex SC600-2 IOL, made by the same manufacturer. The opacification consists of calcium and phosphate.     

Obstructive sleep apnea and the incidence and mortality of gastrointestinal cancers: a systematic review and meta-analysis of 5,120,837 participants

BackgroundEmerging evidence has shown higher overall cancer incidence in patients with obstructive sleep apnea. Gastrointestinal cancers, including esophageal, stomach, liver, pancreas, and colorectal cancers account for 26% of incident cancers. However, the link between gastrointestinal cancers and obstructive sleep apnea is still unclear. We performed a systematic review and meta-analysis (registered PROSPERO CRD42021220836) to investigate the association between obstructive sleep apnea and incidence of gastrointestinal cancer.MethodsWe searched four electronic databases (PubMed, Embase, Cochrane Library, Scopus) and included studies published from inception till 15th November 2020 reporting the association of obstructive sleep apnea with gastrointestinal cancer incidence. Extracted data was meta-analyzed in a random-effects model.ResultsA total of seven studies were included, forming a combined cohort of 5,120,837 patients. Studies which adjusted for demographics and comorbidities were included in meta-analysis. Among four studies with 7–11 years of median follow-up, patients with obstructive sleep apnea experienced increased incidence of colorectal cancer (HR 1.70, 95% CI: 1.48–1.96, I²=22%). Pancreatic cancer incidence was nominally increased in three studies (HR 1.36, 95% CI: 0.88–2.09, I²=96), though this was not statistically significant. There was no association between obstructive sleep apnea and liver cancer incidence among three studies (HR 0.99, 95% CI: 0.81–1.22, I²=84). However, the lack of a statistically significant relationship between obstructive sleep apnea and pancreatic cancer in our meta-analysis does not necessarily imply the true absence of an association.ConclusionsAn increased risk of colorectal cancer was seen in patients with obstructive sleep apnea among studies with long-term follow-up. Further research is required to explore the utility of incorporating obstructive sleep apnea screening into colorectal cancer screening guidelines to identify high-risk individuals and to confirm a possible association of obstructive sleep apnea with pancreatic cancer.PROSPERO RegistrationCRD42021220836