Genome-wide association study between SARS-CoV-2 single nucleotide polymorphisms and virus copies during infections.

Significant variations have been observed in viral copies generated during SARS-CoV-2 infections. However, the factors that impact viral copies and infection dynamics are not fully understood, and may be inherently dependent upon different viral and host factors. Here, we conducted virus whole genome sequencing and measured viral copies using RT-qPCR from 9,902 SARS-CoV-2 infections over a 2-year period to examine the impact of virus genetic variation on changes in viral copies adjusted for host age and vaccination status. Using a genome-wide association study (GWAS) approach, we identified multiple single-nucleotide polymorphisms (SNPs) corresponding to amino acid changes in the SARS-CoV-2 genome associated with variations in viral copies. We further applied a marginal epistasis test to detect interactions among SNPs and identified multiple pairs of substitutions located in the spike gene that have non-linear effects on viral copies. We also analyzed the temporal patterns and found that SNPs associated with increased viral copies were predominantly observed in Delta and Omicron BA.2/BA.4/BA.5/XBB infections, whereas those associated with decreased viral copies were only observed in infections with Omicron BA.1 variants. Our work showcases how GWAS can be a useful tool for probing phenotypes related to SNPs in viral genomes that are worth further exploration. We argue that this approach can be used more broadly across pathogens to characterize emerging variants and monitor therapeutic interventions.

Minimal Pain Tumescent Local Anesthesia Injection for Wide Awake Modified Radical Mastectomy.

The advent of minimal pain tumescent local anesthesia injection has improved patient safety by eliminating the need for sedation for many wide awake operations, especially in patients with significant medical comorbidities. Modified radical mastectomy (MRM) for breast cancer is commonly performed under general anesthesia as it requires the dissection of the entire breast and an ipsilateral axillary lymph node dissection (ALND). General anesthesia has been shown to have a high risk in patients with severe medical comorbidities. We present a case of a 78-year-old male patient who was diagnosed with invasive ductal breast carcinoma, cardiac failure, and other metabolic abnormalities. Taking his comorbidities into account, we performed a wide awake MRM and ALND after tumescent minimal pain local anesthesia injection. The patient experienced the successful procedure safely with minimal discomfort.

L'anesthésie locale par tumescence associée à une douleur minimale a amélioré la sécurité des patients en éliminant la sédation lors de nombreuses opérations éveillées, particulièrement chez les patients qui ont des affections concomitantes importantes. La mastectomie radicale modifiée (MRM) du cancer du sein est souvent effectuée sous anesthésie générale, car elle exige la dissection du sein entier et la dissection des ganglions lymphatiques axillaires (DGLA) ipsilatéraux. Il a été démontré que l'anesthésie générale comporte un risque élevé chez les patients atteints d'affections connexes graves. Les auteurs présentent le cas d'un patient de 78 ans qui a reçu un diagnostic de carcinome canalaire invasif, d'insuffisance cardiaque et d'autres anomalies métaboliques. Compte tenu de ses affections connexes, les médecins ont effectué une MRM et une DGLA après une anesthésie locale par tumescence associée à une douleur minimale. Le patient a subi avec accès une intervention sécuritaire et a éprouvé très peu d'inconfort.

Computational phenotypes for patients with opioid-related disorders presenting to the emergency department.

OBJECTIVE: We aimed to discover computationally-derived phenotypes of opioid-related patient presentations to the ED via clinical notes and structured electronic health record (EHR) data. METHODS: This was a retrospective study of ED visits from 2013-2020 across ten sites within a regional healthcare network. We derived phenotypes from visits for patients ≥18 years of age with at least one prior or current documentation of an opioid-related diagnosis. Natural language processing was used to extract clinical entities from notes, which were combined with structured data within the EHR to create a set of features. We performed latent dirichlet allocation to identify topics within these features. Groups of patient presentations with similar attributes were identified by cluster analysis. RESULTS: In total 82,577 ED visits met inclusion criteria. The 30 topics were discovered ranging from those related to substance use disorder, chronic conditions, mental health, and medical management. Clustering on these topics identified nine unique cohorts with one-year survivals ranging from 84.2-96.8%, rates of one-year ED returns from 9-34%, rates of one-year opioid event 10-17%, rates of medications for opioid use disorder from 17-43%, and a median Carlson comorbidity index of 2-8. Two cohorts of phenotypes were identified related to chronic substance use disorder, or acute overdose. CONCLUSIONS: Our results indicate distinct phenotypic clusters with varying patient-oriented outcomes which provide future targets better allocation of resources and therapeutics. This highlights the heterogeneity of the overall population, and the need to develop targeted interventions for each population.