The rapid spread of the highly contagious Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) along with its high number of mutations in the spike gene has raised alarms ...about the effectiveness of current medical countermeasures. To address this concern, we measured the neutralization of the Omicron BA.1 variant pseudovirus by postvaccination serum samples after two and three immunizations with the Pfizer/BioNTech162b2 SARS-CoV-2 mRNA (Pfizer/BNT162b2) vaccine, convalescent serum samples from unvaccinated individuals infected by different variants, and clinical-stage therapeutic antibodies. We found that titers against the Omicron variant were low or undetectable after two immunizations and in many convalescent serum samples, regardless of the infecting variant. A booster vaccination increased titers more than 30-fold against Omicron to values comparable to those seen against the D614G variant after two immunizations. Neither age nor sex was associated with the differences in postvaccination antibody responses. We also evaluated 18 clinical-stage therapeutic antibody products and an antibody mimetic protein product obtained directly from the manufacturers. Five monoclonal antibodies, the antibody mimetic protein, three antibody cocktails, and two polyclonal antibody preparations retained measurable neutralization activity against Omicron with a varying degree of potency. Of these, only three retained potencies comparable to the D614G variant. Two therapeutic antibody cocktails in the tested panel that are authorized for emergency use in the United States did not neutralize Omicron. These findings underscore the potential benefit of mRNA vaccine boosters for protection against Omicron and the need for rapid development of antibody therapeutics that maintain potency against emerging variants.
A significant minority of people living with HIV (PLWH) achieve viral suppression (VS) on antiretroviral therapy (ART) but do not regain healthy CD4 counts. Clinical factors affecting this immune ...non-response (INR) and its effect on incident serious non-AIDS events (SNAEs) have been challenging to understand due to confounders that are difficult to control in many study settings. The U.S. Military HIV Natural History Study (NHS) and African Cohort Study (AFRICOS). PLWH with sustained VS (< 400 copies/ml for at least two years) were evaluated for INR (CD4 < 350 cells/µl at the time of sustained VS). Logistic regression estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for factors associated with INR. Cox proportional hazards regression produced adjusted hazard ratios (aHRs) for factors associated with incident SNAE after sustained VS. INR prevalence was 10.8% and 25.8% in NHS and AFRICOS, respectively. Higher CD4 nadir was associated with decreased odds of INR (aOR = 0.34 95% CI 0.29, 0.40 and aOR = 0.48 95% CI 0.40, 0.57 per 100 cells/µl in NHS and AFRICOS, respectively). After adjustment, INR was associated with a 61% increase in relative risk of SNAE 95% CI 1.12, 2.33. Probability of "SNAE-free" survival at 15 years since sustained VS was approximately 20% lower comparing those with and without INR; nearly equal to the differences observed by 15-year age groups. CD4 monitoring before and after VS is achieved can help identify PLWH at risk for INR. INR may be a useful clinical indicator of future risk for SNAEs.
Purpose of Review
This review highlights research from the past 5 years on combat trauma-related invasive fungal wound infections (IFIs) with a focus on risk stratification to aid patient management, ...microbiology, and diagnostics.
Recent Findings
A revised classification scheme stratifies wounds into three risk groups: IFI, high suspicion of IFI, and low suspicion of IFI. This stratification is based on persistence of wound necrosis and laboratory fungal evidence, presence of signs/symptoms of deep soft-tissue infections, and the need for antifungals. Use of this classification could allow for prioritization of antifungal therapy. Further, IFIs delay wound healing, particularly when caused by fungi of the order Mucorales. Lastly, molecular sequencing offers promising and complimentary results to the gold standard histopathology.
Summary
Optimal management of combat-related IFIs depends on early tissue-based diagnosis with aggressive surgical debridement and concomitant dual antifungal therapy. Further research on clinical decision support tools and rapid diagnostics is needed.
The prevalence and factors associated with overweight/obesity among human immunodeficiency virus (HIV)-infected persons are unknown.
We evaluated prospective data from a U.S. Military HIV Natural ...History Study (1985-2004) consisting of early diagnosed patients. Statistics included multivariate linear regression and longitudinal linear mixed effects models.
Of 1682 patients, 2% were underweight, 37% were overweight, and 9% were obese at HIV diagnosis. Multivariate predictors of a higher body mass index (BMI) at diagnosis included more recent year of HIV diagnosis, older age, African American race, and earlier HIV stage (all p<0.05). The majority of patients (62%) gained weight during HIV infection. Multivariate factors associated with a greater increase in BMI during HIV infection included more recent year of diagnosis, lower BMI at diagnosis, higher CD4 count, lower HIV RNA level, lack of AIDS diagnosis, and longer HIV duration (all p<0.05). Nucleoside agents were associated with less weight gain; other drug classes had no significant impact on weight change in the HAART era.
HIV-infected patients are increasingly overweight/obese at diagnosis and during HIV infection. Weight gain appears to reflect improved health status and mirror trends in the general population. Weight management programs may be important components of HIV care.
Durable control of human immunodeficiency virus (HIV) replication and lack of disease progression in the absence of antiretroviral therapy were studied in a military cohort of 4586 subjects. We ...examined groups of elite controllers (ie, subjects with plasma HIV RNA levels of <50 copies/mL; prevalence, 0.55% 95% confidence interval {CI}, 0.35%–0.80%), viremic controllers (ie, subjects with plasma HIV RNA levels of 50–2000 copies/mL; prevalence, 3.34% 95% CI, 2.83%–3.91%), and subjects with a lack of disease progression (ie, long-term nonprogressors LTNPs) through 7 years of follow-up (LTNP7s; prevalence, 3.32% 95% CI, 2.70%–4.01%) or 10 years of follow-up (LTNP10s; prevalence, 2.04% 95% CI, 1.52%–2.68%). For elite and viremic controllers, spontaneous virologic control was established early and was typically observed when the initial viral load measurement was obtained within 1 year of estimated seroconversion. Elite controllers had favorable time to development of AIDS (P=.048), a CD4 cell count of 350 cells/μL (P=.009), and more-stable CD4 cell trends, compared with viremic controllers. LTNPs defined by 10-year versus 7-year criteria had a longer survival time (P=.001), even after adjustment for differing periods of invulnerability (P=.042). Definitions of controllers and LTNPs describe distinct populations whose differing clinical outcomes improve with the stringency of criteria, underscoring the need for comparability between study populations
Abstract Objectives The study is aimed to perform magnetic resonance (MR) cartigram of the articular disc in patients with asymptomatic and symptomatic temporomandibular disorders (TMD). Methods ...Thirty-nine volunteers were divided into three groups: 16 symptomatic TMD, 16 asymptomatic TMD, and 7 controls. The articular disc was divided into three segments (anterior, middle, and posterior) and analyzed using morphological magnetic resonance imaging (MRI) and T2 mapping sequences. T2 relaxation values were measured and assessed by an experienced radiologist and two observers. The T2 values in the discs were compared between the control, asymptomatic, and symptomatic groups using the Kruskal–Wallis test. The right and left discs were compared using the Wilcoxon signed rank test. Inter-examiner reliability among different examiners was evaluated. Results The controls had the highest T2 values compared with the other groups. The comparison among the right and left sides of all the groups revealed statistically significant results in the anterior portion in the asymptomatic group and the middle portion in the symptomatic group (p < 0.05). The inter-examiner reliability coefficients among the three examiners were consistently high, with values of 0.921, 0.920, and 0.930. Conclusion Our study found the T2 relaxation time span was shorter than that reported in previous studies, which could be attributed to the early stage of cartilage deterioration in the individuals with TMD inferring treatment at this phase may be eventually effective with a good prognosis.
To describe trends in incidence rates of AIDS-defining cancers (ADCs) and non-AIDS-defining cancers (NADCs) during the HIV epidemic and to evaluate predictors, including the impact of antiretroviral ...therapy, of cancer development.
Retrospective analysis of a multicenter, prospective natural history study including 4498 HIV-infected US military beneficiaries with 33 486 person-years of follow-up.
Predictors evaluated included demographics, clinical data, time-updated CD4 cell counts, HIV viral loads, and antiretroviral history. Time periods were classified as early pre (1984-1990), late pre (1991-1995), early post (1996-2000), and late post (2001-2006) HAART eras. Cox proportional hazard models were used to evaluate the association of specific factors with cancer.
Ten percent of HIV-infected persons developed cancer. ADC rates increased between the early and late pre-HAART eras (7.6 and 14.2 cases per 1000 person-years) and have since declined from 5.4 to 2.7 in the early and late HAART eras, respectively (P < 0.001). Rates of NADCs have risen over the four periods (2.9, 2.8, 4.2, 6.7, P = 0.0004). During the late HAART era, 71% of cancers were NADCs. Predictors for ADCs included low CD4 cell count, noncancer AIDS diagnosis, and lack of HAART. NADCs were predicted by increasing age and white race (due to skin cancers).
Although the rate of ADCs continues to fall, the rate of NADCs is rising and now accounts for the majority of cancers in HIV-infected persons. The development of NADCs is associated with increasing age among HIV patients. HAART use is protective for ADCs, but did not significantly impact NADCs.
To evaluate a classification system to support clinical decisions for treatment of contaminated deep wounds at risk for an invasive fungal infection (IFI), we studied 246 US service members (413 ...wounds) injured in Afghanistan (2009-2014) who had laboratory evidence of fungal infection. A total of 143 wounds with persistent necrosis and laboratory evidence were classified as IFI; 120 wounds not meeting IFI criteria were classified as high suspicion (patients had localized infection signs/symptoms and had received antifungal medication for >10 days), and 150 were classified as low suspicion (failed to meet these criteria). IFI patients received more blood than other patients and had more severe injuries than patients in the low-suspicion group. Fungi of the order Mucorales were more frequently isolated from IFI (39%) and high-suspicion (21%) wounds than from low-suspicion (9%) wounds. Wounds that did not require immediate antifungal therapy lacked necrosis and localized signs/symptoms of infection and contained fungi from orders other than Mucorales.
Variation in the 3′ untranslated region (3′UTR) of the HLA-C locus determines binding of the microRNA Hsa-miR-148a, resulting in lower cell surface expression of alleles that bind miR-148a relative ...to those alleles that escape its binding. The HLA-C 3′UTR variant was shown to associate with HIV control, but like the vast majority of disease associations in a region dense with causal candidates, a direct effect of HLA-C expression level on HIV control was not proven. We demonstrate that a MIR148A insertion/deletion polymorphism associates with its own expression levels, affecting the extent to which HLA-C is down-regulated, the level of HIV control, and the risk of Crohn disease only among those carrying an intact miR-148a binding site in the HLA-C 3′UTR. These data illustrate a direct effect of HLA-C expression level on HIV control that cannot be attributed to other HLA loci in linkage disequilibrium with HLA-C and highlight the rich complexity of genetic interactions in human disease.
Context: Frequent monitoring of glucose is important in the management of diabetes. A noninvasive painless technique was used to detect glucose levels with the use of saliva as a diagnostic fluid. ...Aims: The aim of our study was to correlate the blood glucose levels with stimulated and unstimulated salivary samples and also to assess the reliability of using salivary glucose in diagnosing and monitoring the blood glucose levels in gestational diabetic patients. Settings and Design: The study was conducted among 100 clinically healthy nondiabetic individuals and 99 individuals suffering from gestational diabetes mellitus (GDM). Subjects and Methods: Fasting blood glucose estimation and postprandial salivary glucose estimation were done in stimulated and unstimulated salivary samples using glucose oxidase/peroxidase method. Statistical Analysis Used: Data obtained were subjected to normality test, and P ≤ 0.05 was considered to be statistically significant. The correlation between blood and salivary glucose levels was evaluated using Pearson's correlation test. Results: A positive correlation was obtained for stimulated and unstimulated salivary samples in fasting and postprandial conditions. Linear regression analysis and receiver operating characteristic curve were plotted, and the optimal cutoff value for unstimulated and stimulated salivary glucose under fasting conditions was 5.1 mg/dl and 5.4 mg/dl, respectively. The optimal cutoff value for unstimulated and stimulated salivary glucose was 8.8 mg/dl and 9.3 mg/dl, respectively, in postprandial conditions. Conclusions: Saliva appears to be a reliable biofluid to assess the blood glucose levels and can definitely be a reliable alternative to blood glucose in GDM patients.
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