Wednesday, February 1, 2023

Emerging Omicron subvariants evade neutralizing immunity elicited by vaccine or BA.1/BA.2 infection

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Abstract

The newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2.75 and BA.2.76 subvariants contained 35 and 29 additional mutations in its spike (S) protein compared to the reference SARS-CoV-2 genome, respectively. Here, we measured the evasion degree of the BA.1, BA.2, BA.4, BA.5, BA.2.75, and BA.2.76 subvariants from neutralizing immunity in people previously infected with the Omicron BA.1 and BA.2, determined the effect of vaccination on immune evasion, and compared the titers of neutralizing antibodies in serums between acute infection and convalescence. Results showed that the neutralization effect of serums from patients with different vaccination statuses and BA.1/BA.2 breakthrough infection decreased with the Omicron evolution from BA.1 to BA.2, BA.4, BA.5, BA.2.75, and BA.2.76. This study also indicated that the existing vaccines could no longer provide effective protection, especially for the emerging BA.2.75 and BA.2.76 subvariants. Therefo re, vaccines against emerging epidemic strains should be designed specifically. In the future, we can not only focus on the current strains, but also predict and design new vaccines against potential mutant strains. At the same time, we can combine the virus strains' infection characteristics to develop protective measures for virus colonization areas, such as nasal protection spray. Besides, further studies on the Y248N mutation of BA.2.76 subvariant were also necessary to explore its contribution to the enhanced immune evasion ability.

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Severe Mpox Infections in People with Uncontrolled Human Immunodeficiency Virus (HIV)

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Abstract
In the current mpox outbreak, infections are usually self-limited. We describe three patients with uncontrolled HIV and mpox infections lasting months, causing debilitating lesions, complications, and death, despite initiating anti-mpox and antiretroviral therapy. Delayed treatment of mpox with antiviral agents may contribute to poor outcomes in severely immunocompromised patients.
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Clostridioides difficile near patient testing versus centralized testing: A pragmatic cluster randomized cross-over trial

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Abstract
Background
Management of suspected C. difficile infections (CDI) in the hospital setting typically results in patient isolation, laboratory testing, infection control, and presumptive treatment. We investigated whether implementation of rapid near patient testing (NPT) reduced patient isolation time, hospital length of stay, antibiotic usage, and cost.
Methods
A two-period pragmatic cluster randomized crossover trial was conducted. 39 wards were randomized into two study arms. The primary outcome measure was effect of NPT on patient isolation time using a mixed effect generalized linear regression model. Secondary outcomes examined included hospital length of stay and antibiotic therapy based on a negative binomial regression model. Natural experiment (NE), intention-to-treat (ITT), and per protocol (PP) analyses was conducted.
Results
During the entire study period, a total of 656 patients received NPT for CDI and 166 7 received SOC testing. For the primary outcome, a significant decrease of patient isolation time with NPT was observed (NE 9.4 hours [p<0.01], ITT 2.3 [p<0.05], PP 6.7[p<0.1]). A significant reduction in hospital length of stay was observed with NPT for short stay (NE 47.4% [p<0.01], ITT 18.4% [p<0.01] and ITT 34.2% [p<0.01]). Each additional hour delay for a negative result increased metronidazole use (24 DDD per 1000 patients, p<0.05) and non-CDI treating antibiotics by 70.13 mg (p<0.01). NPT testing was found to save USD25.48 per patient when including test cost and patient isolation.
Conclusions
The cluster randomized cross-over trial demonstrated that implementation of CDI NPT can contribute to significant reductions in isolation time, hospital length of stay, antibiotic usage, and health care cost.
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A lifestyle pattern characterized by high consumption of sweet and salty snacks, sugar sweetened beverages and sedentary time is associated with blood pressure in families at risk for type 2 diabetes mellitus in Europe. The Feel4Diabetes Study.

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Abstract

Objective

Individuals from families at high-risk for type 2 diabetes mellitus (T2DM) are also in high risk for hypertension and cardiovascular disease. Studies identifying lifestyle patterns combining dietary, physical activity or sedentary variables and examining their possible role to developing blood pressure (BP) are limited. This study aimed to examine the association of different lifestyle patterns (LPs) with BP levels in families at high risk for T2DM in Europe.

Research Methods & Procedures

1844 adults (31.6% males) at high-risk for T2DM across 6 European countries were included in this cross-sectional study using data from the baseline assessment of the Feel4Diabetes Study. BP measurements, dietary and physical activity assessments were conducted, and screen times was surveyed. Lifestyle patterns were revealed with Principal Component Analysis (PCA) of various data regarding diet, physical activity, screen time and smoking.

Results

3 LPs were identified, LP3 (high consumption of sweet & salty snacks, sugar sweetened soft drinks and juices and high amount of screen time) was positively associated with diastolic BP [B, 0.52 95%CI (0.05-0.99)] and existence of hypertension [OR,1.12 95%CI (1.00-1.25)]. Participants in the highest tertile of LP3 spent mean 3 hours of screen time, consumed 1.5 portions of sweet and/or salty snacks and 1 liter of soft drinks on a daily basis, were associated with 12% higher risk of hypertension.

Conclusion

Focusing on the combination of eating and lifestyle behaviors may more accurately identify, and therefore guide preventive measures tailored to the specific needs of high-risk populations.

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Functional consequence and therapeutic targeting of cryptic ALK fusions in monosomy 7 acute myeloid leukemia

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Abstract

Acute myeloid leukemia (AML) patients have a wide array of cytogenetic and molecular aberrations, which can influence response to therapy. Monosomy 7 is a rare subset within pediatric AML (prevalence of <2%) that is highly associated with poor outcomes. Fusions involving the anaplastic tyrosine kinase (ALK) gene were exclusively identified in 14.3% of this high-risk cohort, while absent across all other AML. Given the dismal outcomes of monosomy 7, we evaluated the use of crizotinib, an FDA-approved tyrosine kinase inhibitor, used to treat patients with ALK fusions. Our findings suggest that crizotinib may serve as a novel therapy for these patients.
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A Micro‐Computed Tomography Analysis of Internal and Marginal Fit of Fixed Partial Dentures: Effect of Preparation Finish Line Designs on Monolithic Zirconia and Heat‐Pressed Zirconia Reinforced Lithium Disilicate

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Abstract

Purpose

: To evaluate the effect of finish line design (chamfer and feather-edge) and ceramic type on the internal and marginal fit of fixed partial dentures on abutment teeth.

Materials and Methods

: Two typodont mandibular casts, missing right first premolar tooth, received tooth preparation on canine and second premolar abutments (one cast with chamfer finish line and the other cast with feather-edge finish line). The preparation segment of each typodont model was scanned, 3D printed in resin, then invested and casted in metal to obtain two metal models. Polyvinyl siloxane impressions were made for the metal models and poured in type IV stone. The stone models (n = 40) were randomly assigned into four groups (n = 10): chamfer finish line with heat-pressed zirconia re-inforced lithium disilicate fixed partial denture (CL), chamfer finish line with monolithic zirconia fixed partial denture (CZ), feather-edge finish line with heat-pressed zirconia re-inforced lithium disilicate fixed partial denture (FL), and feather-edge finish line with monolithic zirconia fixed partial denture (FZ). After the fabrication of ceramic restoration, micro-computed tomography was used to evaluat e the internal and marginal fit of each fixed partial denture. Data were statistically analyzed with three-way ANOVA (α = 0.05).

Results

: There were no significant interactions between preparation type, material type, and tooth type at any of the areas assessed. There was significant difference (p = 0.01) between CZ (59.15 ±4.6 μm) and FZ (73.6 ±17.1 μm) groups at the finish line area. Regarding the horizontal marginal discrepancy area, there were significant differences between CZ (62.65 ±10.5 μm) and FZ (90.05 ±5.6 μm) groups (p ˂0.001), CL (77.45 ±8.1 μm) and CZ (62.65 ±10.5 μm) groups (p ˂0.001), and FZ (90.05 ±5.6 μm) and CL (77.45 ±8.1 μm) groups (p˂0.001). At finish line area, there was a significant difference (p = 0.018) between feather-edge with canine (72.75 ±13.3 μm) and chamfer with canine (59.05 ±5.8 μm), however there was no significant difference (p = 0.774) between feather-edge with premolar (69.45 ±12 μm) and chamfer with premolar (65.1 ±7.4 μm). Also, there was no significant difference (p = 0.886) between feather-edge with canine and feather-edge with premolar.

Conclusions

: The internal and marginal fit of the ceramic fixed partial dentures can be affected by the finish line design and ceramic type. The feather-edge finish line had a negative impact on the marginal and internal fit of ceramic fixed partial dentures at certain measurement points. Regarding the effect of finish line design on abutment teeth, the difference in fit was only detected at the finish line area of the anterior abutment (canine) with the feather-edge finish line

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Effect of finish line location and saliva contamination on the accuracy of crown finish line scanning

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Abstract

Purpose

Intraoral scanners are used widely as an alternative to conventional impressions, but studies on the influence of finish line location and saliva contamination on scanning trueness are lacking. The purpose of this in vitro study was to evaluate the influence of finish line location and saliva contamination on the scanning trueness of crown finish lines.

Materials and Methods

Three ivorine teeth were prepared for all-ceramic crowns with finish lines placed equigingivally, 0.5 mm subgingivally, and 1.0 mm subgingivally. A single-cord technique was used for gingival retraction and a total of 180 intraoral scans were made using two intraoral scanners (Emerald; Planmeca USA Inc., Hoffman Estates, IL & Trios3; 3Shape A/S, Copenhagen, Denmark). The prepared teeth were separated from the dentoform and scanned using the same intraoral scanners to create reference scans. All scans were imported to the design software (Dental System 2019; 3Shape A/S, Copenhagen, Denmark). After marking the finish lines of prepared teeth, intraoral scans were aligned to the reference scans for comparisons. Vertical and horizontal marginal discrepancies were measured at 4 different measuring points (buccal, lingual, mesial, and distal) and analyzed. Two-way ANOVA and Tukey HSD tests were used for statistical analysis (α = 0.05).

Results

The average vertical and horizontal discrepancies from various groups ranged from -33μm to 440μm. For both intraoral scanners, subgingival finish line groups showed greater vertical and horizontal discrepancies compared with equigingival finish line groups. Saliva contamination significantly increased both vertical and horizontal discrepancies for all finish line locations. The discrepancy increases due to saliva contamination were greater for the subgingival groups.

Conclusions

Subgingival finish lines were not accurately captured using the intraoral scanners. The presence of saliva significantly reduced scanning trueness and this was amplified when the finish lines were located subgingivally.

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Application of radiomics to meningiomas: a systematic review

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Abstract
Background
Quantitative imaging analysis through radiomics is a powerful technology to non-invasively assess molecular correlates and guide clinical decision-making. There has been growing interest in image-based phenotyping for meningiomas given complexities in management.
Methods
We systematically reviewed meningioma radiomics analyses published in PubMed, Embase, and Web of Science until 12/20/2021. We compiled performance data and assessed publication quality using the Radiomics Quality Score (RQS).
Results
170 publications were grouped into five categories of radiomics applications to meningiomas: tumor detection and segmentation (21%), classification across neurologic diseases (54%), grading (14%), feature correlation (3%), and prognostication (8%). A majority focused on technical model development (73%) versus clinical applications (27%), with increasing adoption of deep learning. Studies utilized either private institutional (50%) or public (49%) datasets, with only 68% using a validation dataset. For detection and segmentation, radiomic models had a mean accuracy of 93.1±8.1% and a dice coefficient of 88.8±7.9%. Meningioma classification had a mean accuracy of 95.2±4.0%. Tumor grading had a mean AUC of 0.85±0.08. Correlation with meningioma biological features had a mean AUC of 0.89±0.07.Prognostication of clinical course had a mean AUC of 0.83±0.08. While clinical studies had a higher mean RQS compared to technical studies, quality was low overall with a mean RQS of 6.7±5.9 (possible range -8 to 36).
Conclusion
There has been global growth in meningioma radiomics, driven by data accessibility and novel computational methodology. Translatability toward complex tasks such as prognostication requires studies that improve quality, develop comprehensive patient datasets, and engage in prospective trials.
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Short-term Air Pollution Levels and Blood Pressure in Older Women

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imageBackground: Evidence of associations between daily variation in air pollution and blood pressure (BP) is varied and few prior longitudinal studies adjusted for calendar time. Methods: We studied 143,658 postmenopausal women 50 to 79 years of age from the Women's Health Initiative (1993–2005). We estimated daily atmospheric particulate matter (PM) (in three size fractions: PM2.5, PM2.5-10, and PM10) and nitrogen dioxide (NO2) concentrations at participants' residential addresses using validated lognormal kriging models. We used linear mixed-effects models to estimate the association between air pollution concentrations and repeated measures of systolic and diastolic BP (SBP, DBP) adjusting for confounders and calendar time. Results: Short-term PM2.5 and NO2 were each positively associated with DBP {0.10 mmHg [95% confidence interval (CI): 0.04, 0.15]; 0.13 mmHg (95% CI: 0.09, 0.18), respectively} for interquartile range changes in lag 3-5 day PM2.5 and NO2. Short-term NO2 was negatively associated with SBP [−0.21 mmHg (95%CI: −0.30, −0.13)]. In two-pollutant models, the NO2–DBP association was slightly stronger, but for PM2.5 was attenuated to null, compared with single-pollutant models. Associations between short-term NO2 and DBP were more pronounced among those with higher body mass index, lower neighborhood socioeconomic position, and diabetes. When long-term (annual) and lag 3-5 day PM2.5 were in the same model, associations with long-term PM2.5 were stronger than for lag 3-5 day. Conclusions: We observed that short-term PM2.5 and NO2 levels were associated with increased DBP, although two-pollutant model results suggest NO2 was more likely responsible for observed associations. Long-term PM2.5 effects were larger than short-term.
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