Is frontal EEG gamma power a neural correlate of language in toddlerhood? An examination of late talking and expressive language ability.

Few studies have examined neural correlates of late talking in toddlers, which could aid in understanding etiology and improving diagnosis of developmental language disorder (DLD). Greater frontal gamma activity has been linked to better language skills, but findings vary by risk for developmental disorders, and this has not been investigated in late talkers. This study examined whether frontal gamma power (30-50 Hz), from baseline-state electroencephalography (EEG), was related to DLD risk (categorical late talking status) and a continuous measure of expressive language in n = 124 toddlers. Frontal gamma power was significantly associated with late talker status when controlling for demographic factors and concurrent receptive language (ß = 1.96, McFadden's Pseudo R2 = 0.21). Demographic factors and receptive language did not significantly moderate the association between frontal gamma power and late talker status. A continuous measure of expressive language ability was not significantly associated with gamma (r = -0.07). Findings suggest that frontal gamma power may be useful in discriminating between groups of children that differ in DLD risk, but not for expressive language along a continuous spectrum of ability.

The development and structure of the HEALthy Brain and Child Development (HBCD) Study EEG protocol.

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. Electroencephalography (EEG) is one of two brain imaging modalities central to the HBCD Study. EEG records electrical signals from the scalp that reflect electrical brain activity. In addition, the EEG signal can be synchronized to the presentation of discrete stimuli (auditory or visual) to measure specific cognitive processes with excellent temporal precision (e.g., event-related potentials; ERPs). EEG is particularly helpful for the HBCD Study as it can be used with awake, alert infants, and can be acquired continuously across development. The current paper reviews the HBCD Study's EEG/ERP protocol: (a) the selection and development of the tasks (Video Resting State, Visual Evoked Potential, Auditory Oddball, Face Processing); (b) the implementation of common cross-site acquisition parameters and hardware, site setup, training, and initial piloting; (c) the development of the preprocessing pipelines and creation of derivatives; and (d) the incorporation of equity and inclusion considerations. The paper also provides an overview of the functioning of the EEG Workgroup and the input from members across all steps of protocol development and piloting.

Respiratory-swallow patterning and oropharyngeal swallowing impairment in patients undergoing evaluation for lung transplant.

BACKGROUND: Although swallowing impairment is prevalent following lung transplantation, baseline respiratory and swallowing characteristics are often overlooked. Respiratory disease processes may predispose lung transplant candidates to altered respiratory-swallow patterning and swallowing impairment. METHODS: This cross-sectional study included patients referred for a Modified Barium Swallow Study during lung transplant evaluation. Swallowing impairment was measured using the Modified Barium Swallow Impairment Profile and Penetration-Aspiration Scale. Respiratory plethysmographic signals synchronized with videofluoroscopy were analyzed to determine phase patterning, pause duration, and rate. Mixed-effects logistic regression was used to identify linkages between respiratory and swallowing measures. KEY RESULTS: Fifty patients were included and demonstrated delayed swallow initiation (49/50), oral residue (37/50), incomplete pharyngoesophageal segment opening (35/50), and esophageal retention (43/50). Airway invasion occurred infrequently (10/50). Atypical respiratory patterning was significantly associated with impairment in pharyngeal swallow initiation (OR [95% CI] = 1.76 [1.16, 2.68], p = 0.009), laryngeal elevation (OR [95% CI] = 1.45 [1.01, 2.07], p = 0.044), and laryngeal vestibular closure (OR [95% CI] = 2.57 [1.48, 4.46], p < 0.001). Increased pause duration was associated with impaired initiation (OR [95% CI] = 2.24 [1.20, 4.16], p = 0.011), laryngeal elevation (OR [95% CI] = 1.18 [1.03, 1.36], p = 0.018), laryngeal closure (OR [95% CI] = 1.28 [1.9, 1.50], p = 0.003), and tongue base retraction (OR [95% CI] = 1.33 [1.13, 1.56], p < 0.001). CONCLUSIONS & INFERENCES: Patients undergoing evaluation for lung transplant demonstrated impaired swallowing and phase patterning. Preliminary findings implicate the need for further evaluation of respiratory-swallow coordination and its potential role in swallowing impairment before and after lung transplantation.

Risk of healthcare visits from influenza in subjects with diabetes and impacts of early vaccination.

INTRODUCTION: The objective of this study was to determine the burden of influenza disease in patients with or without diabetes in a population of American adults to understand the benefits of seasonal vaccination. RESEARCH DESIGN AND METHODS: We performed a retrospective cohort study using electronic medical records totaling 1,117,263 from two Louisiana healthcare providers spanning January 2012 through December 2017. Adults 18 years or older with two or more records within the study period were included. The primary outcome quantified was influenza-related diagnosis during inpatient (IP) or emergency room (ER) visits and risk reduction with the timing of immunization. RESULTS: Influenza-related IP or ER visits totaled 0.0122-0.0169 events per person within the 2013-2016 influenza seasons. Subjects with diabetes had a 5.6-fold more frequent influenza diagnosis for IP or ER visits than in subjects without diabetes or 3.7-fold more frequent when adjusted for demographics. Early immunization reduced the risk of influenza healthcare utilization by 66% for subjects with diabetes or 67% for subjects without diabetes when compared with later vaccination for the 2013-2016 influenza seasons. Older age and female sex were associated with a higher incidence of influenza, but not a significant change in risk reduction from vaccination. CONCLUSIONS: The risk for influenza-related healthcare utilization was 3.7-fold higher if patients had diabetes during 2013-2016 influenza seasons. Early immunization provides a significant benefit to adults irrespective of a diabetes diagnosis. All adults, but particularly patients with diabetes, should be encouraged to get the influenza vaccine at the start of the influenza season.

Is there a role for vaccines in combatting the opioid epidemic?

Fentanyl is at the center of the opioid crisis in the USA, causing an increasing number of overdoses and deaths. Casey Nevins, Assistant Editor, Vaccine Insights, speaks with Elizabeth Norton, Associate Professor, Tulane School of Medicine, about her work in developing a mucosal vaccination tailored to protect the brain from the effects of fentanyl.

Incidence, risk factors, and long-term outcomes associated with permanent pacemaker implantation after aortic root replacement.

OBJECTIVE: Permanent pacemaker implantation (PPI) after aortic valve replacement is associated with long-term mortality. However, data regarding PPI after aortic root replacement (ARR) is lacking. Herein we describe the incidence, risk factors, and long-term outcomes of PPI after ARR. METHODS: Consecutive patients undergoing ARR from 2005 to 2020 were selected after excluding those with endocarditis, type A dissection, or preoperative PPI. Patients requiring PPI after ARR were identified, along with the indication and timing. Independent factors associated with PPI after ARR were identified and long-term survival was assessed. RESULTS: The incidence of PPI was 3.8% (n = 85) among 2240 patients undergoing ARR. PPI was performed a median of 7 days (interquartile range, 5-12 days) after ARR most commonly for complete heart block (73%). Bicuspid aortic valve (odds ratio [OR], 1.89; P = .02), female sex (OR, 1.74; P = .04), preoperative heart block (OR, 2.70; P = .02), and prior aortic valve replacement (OR, 2.18; P = .01) were independently associated with PPI while preoperative aortic insufficiency (OR, 0.52; P = .01) and valve-sparing root replacement procedure compared with bio-Bentall (OR, 0.40; P = .01) were protective. Patients requiring PPI after ARR were not at increased risk of operative or long-term mortality compared with patients not requiring PPI (P = .26); however, those undergoing PPI experienced significantly longer hospital length of stay (13 vs 7 days; P < .001). CONCLUSIONS: The incidence of PPI after ARR remains low, particularly after VSRR. Preoperative conduction disturbance, prior AVR, and bicuspid aortic valve are all associated with increased risk of PPI. Although PPI is associated with longer length of stay, it is not associated with early or late mortality.

Continuous Glucose Monitoring-Derived Differences in Pregnancies With and Without Adverse Perinatal Outcomes.

OBJECTIVE: To evaluate whether continuous glucose monitoring (CGM)-derived glycemic patterns observed throughout pregnancy were associated with adverse perinatal outcomes, specifically fetal growth disorders and hypertensive disorders of pregnancy (HDP). METHODS: We conducted a prospective observational study of individuals with viable singleton pregnancies and screening hemoglobin A1c levels less than 6.5%. Those with preexisting diabetes were excluded. Enrollment occurred at the earliest gestational age before 17 weeks. Participants wore blinded continuous glucose monitors consecutively as willing until delivery. Those with at least 14 days of CGM data were included in analysis. Rates of large-for-gestational-age (LGA) neonates, small-for-gestational age (SGA) neonates, and HDP were assessed. Continuous glucose monitoring-derived glycemic metrics were calculated, including mean glucose level and percent time above and below thresholds. Two-sample t tests were used to compare glycemic metrics between participants with and without adverse perinatal outcomes. RESULTS: Of 937 participants enrolled, 760 met inclusion criteria. Those delivering LGA neonates or who were diagnosed with HDP had higher mean glucose levels (102±9 vs 100±8, P=.01 and 103±8 vs 99±8, P<.001) and spent more time above 120 mg/dL (median 16% vs 12%, P=.006, and 16% vs 12%, P<.001, respectively) and above 140 mg/dL (median 3.9% vs 2.8%, P=.006, and 3.5% vs 2.8%, P<.001, respectively) throughout gestation than those without these outcomes. These findings were present regardless of gestational diabetes mellitus status. Participants with SGA neonates had lower mean glucose levels (97±7 vs 101±8, P=.01) and spent less time above 140 mg/dL (median 1.6% vs 2.3%, P=.01) and more time below 63 mg/dL (median 3.0% vs 2.3%, P=.02) than those without SGA neonates. CONCLUSION: Individuals with LGA neonates or HDP exhibit a slightly higher mean glucose levels and spend more time hyperglycemic in early pregnancy than those who do not experience these outcomes.

Continuous Glucose Monitoring Prediction of Gestational Diabetes Mellitus and Perinatal Complications.

Objective: To assess the performance of continuous glucose monitoring (CGM)-measured glycemic metrics in predicting development of gestational diabetes mellitus (GDM) and select perinatal complications. Research Methods: In a prospective observational study, CGM data were collected from 760 pregnant females throughout gestation after study enrollment. GDM was diagnosed using the oral glucose tolerance test (OGTT) at 24-34 weeks of gestation. Predictive models were built using logistic and elastic net regression. Predictive performance was assessed by the area under the receiver-operating characteristic (AUROC) curve. Results: The AUROCs of using second trimester percent time >140 mg/dL (TA140) and week 13-14 TA140 in predicting GDM were 0.81 and 0.74, respectively. The AUROCs for predicting large-for-gestational-age (LGA) births and hypertensive disorders of pregnancy (HDP) using second trimester TA140 were both 0.58. When matching the specificity of OGTT, a model using TA140 in weeks 13-14 achieved similar sensitivity to OGTT in predicting HDP (13% vs. 10%, respectively) and LGA (6% for both methods). Elastic net also demonstrated similar AUROC and diagnostic performance with no meaningful improvement by using multiple predictors. Conclusion: CGM-measured hyperglycemic metrics such as TA140 predicted GDM with high AUROCs as early as 13-14 weeks of gestation. These metrics were also similar statistically to the OGTT at 24-34 weeks in predicting perinatal complications, although sensitivity was low for both. CGM could potentially be used as an early screening tool for elevated hyperglycemia during gestation, which could be used in addition to or instead of the OGTT.

Long-term outcomes after aortic root replacement for bicuspid aortic valve-associated aneurysm.

OBJECTIVE: Patients with congenital bicuspid aortic valve often require root replacement. This study aims to describe their long-term rates of mortality and reoperation. METHODS: This is a multicenter retrospective study of 747 patients with bicuspid aortic valve who underwent aortic root replacement for aortic aneurysm between 2004 and 2020. Cumulative incidence curves for aortic valve and aortic reoperations were graphed. A Kaplan-Meier survival curve for the patient cohort was created alongside an age- and sex-matched curve for the US population. Multivariable Cox regression was used to determine characteristics associated with long-term mortality. RESULTS: The median age of our cohort was 54 [43-64] years old, and 101 (13.5%) patients were female. In patients with bicuspid aortic valve dysfunction, 274 (36.7%) had aortic insufficiency, 187 (25.0%) had aortic stenosis, and 142 (19.0%) had both. In-hospital mortality occurred in 10 (1.3%) patients. There were 56 aortic valve reoperations and 19 aortic reoperations, with a combined cumulative incidence of 35% (95% confidence interval [CI], 23%-46%) at 15 years. In addition, there was comparable survival between the patient cohort and the age- and sex-matched US population. Age (hazard ratio [HR], 1.04; 95% CI, 1.01-1.06), concomitant CABG (HR, 2.28; 95% CI, 1.29-4.04), and bypass time (HR, 1.01; 95% CI, 1.00-1.01) were associated with increased mortality. CONCLUSIONS: Patients who undergo aortic root replacement with bicuspid aortic valve have an increased rate of aortic reoperation (35%; 95% CI, 23%-46%) while their survival appears to be comparable to the general US population (79%; 95% CI, 73%-87%) at 15 years.

Glucose levels measured with continuous glucose monitoring in uncomplicated pregnancies.

INTRODUCTION: To characterize glucose levels during uncomplicated pregnancies, defined as pregnancy with a hemoglobin A1c <5.7% (<39 mmol/mol) in early pregnancy, and without a large-for-gestational-age birth, hypertensive disorders of pregnancy, or gestational diabetes mellitus (ie, abnormal oral glucose tolerance test). RESEARCH DESIGN AND METHODS: Two sites enrolled 937 pregnant individuals aged 18 years and older prior to reaching 17 gestational weeks; 413 had an uncomplicated pregnancy (mean±SD body mass index (BMI) of 25.3±5.0 kg/m2) and wore Dexcom G6 continuous glucose monitoring (CGM) devices throughout the observed gestational period. Mealtimes were voluntarily recorded. Glycemic levels during gestation were characterized using CGM-measured glycemic metrics. RESULTS: Participants wore CGM for a median of 123 days each. Glucose levels were nearly stable throughout all three trimesters in uncomplicated pregnancies. Overall mean±SD glucose during gestation was 98±7 mg/dL (5.4±0.4 mmol/L), median per cent time 63-120 mg/dL (3.5-6.7 mmol/L) was 86% (IQR: 82-89%), median per cent time <63 mg/dL (3.5 mmol/L) was 1.8%, median per cent time >120 mg/dL (6.7 mmol/L) was 11%, and median per cent time >140 mg/dL (7.8 mmol/L) was 2.5%. Mean post-prandial peak glucose was 126±22 mg/dL (7.0±1.2 mmol/L), and mean post-prandial glycemic excursion was 36±22 mg/dL (2.0±1.2 mmol/L). Higher mean glucose levels were low to moderately associated with pregnant individuals with higher BMIs (103±6 mg/dL (5.7±0.3 mmol/L) for BMI ≥30.0 kg/m2 vs 96±7 mg/dL (5.3±0.4 mmol/L) for BMI 18.5-<25 kg/m2, r=0.35). CONCLUSIONS: Mean glucose levels and time 63-120 mg/dL (3.5-6.7 mmol/L) remained nearly stable throughout pregnancy and values above 140 mg/dL (7.8 mmol/L) were rare. Mean glucose levels in pregnancy trend higher as BMI increases into the overweight/obesity range. The glycemic metrics reported during uncomplicated pregnancies represent treatment targets for pregnant individuals.

Continuous Glucose Monitoring Profiles in Pregnancies With and Without Gestational Diabetes Mellitus.

OBJECTIVE: To determine whether continuous glucose monitoring (CGM)-derived glycemic patterns can characterize pregnancies with gestational diabetes mellitus (GDM) as diagnosed by standard oral glucose tolerance test at 24-28 weeks' gestation compared with those without GDM. RESEARCH DESIGN AND METHODS: The analysis includes 768 individuals enrolled from two sites prior to 17 weeks' gestation between June 2020 and December 2021 in a prospective observational study. Participants wore blinded Dexcom G6 CGMs throughout gestation. Main outcome of interest was a diagnosis of GDM by oral glucose tolerance test (OGTT). Glycemic levels in participants with GDM versus without GDM were characterized using CGM-measured glycemic metrics. RESULTS: Participants with GDM (n = 58 [8%]) had higher mean glucose (109 ± 13 vs. 100 ± 8 mg/dL [6.0 ± 0.7 vs. 5.6 ± 0.4 mmol/L], P < 0.001), greater glucose SD (23 ± 4 vs. 19 ± 3 mg/dL [1.3 ± 0.2 vs. 1.1 ± 0.2 mmol/L], P < 0.001), less time in range 63-120 mg/dL (3.5-6.7 mmol/L) (70% ± 17% vs. 84% ± 8%, P < 0.001), greater percent time >120 mg/dL (>6.7 mmol/L) (median 23% vs. 12%, P < 0.001), and greater percent time >140 mg/dL (>7.8 mmol/L) (median 7.4% vs. 2.7%, P < 0.001) than those without GDM throughout gestation prior to OGTT. Median percent time >120 mg/dL (>6.7 mmol/L) and time >140 mg/dL (>7.8 mmol/L) were higher as early as 13-14 weeks of gestation (32% vs. 14%, P < 0.001, and 5.2% vs. 2.0%, P < 0.001, respectively) and persisted during the entire study period prior to OGTT. CONCLUSIONS: Prior to OGTT at 24-34 weeks' gestation, pregnant individuals who develop GDM have higher CGM-measured glucose levels and more hyperglycemia compared with those who do not develop GDM.

Vaccine-elicited IL-1R signaling results in Th17 TRM-mediated immunity.

Lung tissue resident memory (TRM) cells are thought to play crucial roles in lung host defense. We have recently shown that immunization with the adjuvant LTA1 (derived from the A1 domain of E. coli heat labile toxin) admixed with OmpX from K. pneumoniae can elicit antigen specific lung Th17 TRM cells that provide serotype independent immunity to members of the Enterobacteriaceae family. However, the upstream requirements to generate these cells are unclear. Single-cell RNA-seq showed that vaccine-elicited Th17 TRM cells expressed high levels of IL-1R1, suggesting that IL-1 family members may be critical to generate these cells. Using a combination of genetic and antibody neutralization approaches, we show that Th17 TRM cells can be generated independent of caspase-1 but are compromised when IL-1α is neutralized. Moreover IL-1α could serve as a molecular adjuvant to generate lung Th17 TRM cells independent of LTA1. Taken together, these data suggest that IL-1α plays a major role in vaccine-mediated lung Th17 TRM generation.

Altered COVID-19 immunity in children with asthma by atopic status.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes a spectrum of clinical outcomes that may be complicated by severe asthma. Antiviral immunity is often compromised in patients with asthma; however, whether this is true for SARS-CoV-2 immunity and children is unknown. Objective: We aimed to evaluate SARS-CoV-2 immunity in children with asthma on the basis of infection or vaccination history and compared to respiratory syncytial viral or allergen (eg, cockroach, dust mite)-specific immunity. Methods: Fifty-three children from an urban asthma study were evaluated for medical history, lung function, and virus- or allergen-specific immunity using antibody or T-cell assays. Results: Polyclonal antibody responses to spike were observed in most children from infection and/or vaccination history. Children with atopic asthma or high allergen-specific IgE, particularly to dust mites, exhibited reduced seroconversion, antibody magnitude, and SARS-CoV-2 virus neutralization after SARS-CoV-2 infection or vaccination. TH1 responses to SARS-CoV-2 and respiratory syncytial virus correlated with antigen-respective IgG. Cockroach-specific T-cell activation as well as IL-17A and IL-21 cytokines negatively correlated with SARS-CoV-2 antibodies and effector functions, distinct from total and dust mite IgE. Allergen-specific IgE and lack of vaccination were associated with recent health care utilization. Reduced lung function (forced expiratory volume in 1 second ≤ 80%) was independently associated with (SARS-CoV-2) peptide-induced cytokines, including IL-31, whereas poor asthma control was associated with cockroach-specific cytokine responses. Conclusion: Mechanisms underpinning atopic and nonatopic asthma may complicate the development of memory to SARS-CoV-2 infection or vaccination and lead to a higher risk of repeated infection in these children.

Intranasal SARS-CoV-2 RBD decorated nanoparticle vaccine enhances viral clearance in the Syrian hamster model.

Multiple vaccines have been developed and licensed for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). While these vaccines reduce disease severity, they do not prevent infection. To prevent infection and limit transmission, vaccines must be developed that induce immunity in the respiratory tract. Therefore, we performed proof-of-principle studies with an intranasal nanoparticle vaccine against SARS-CoV-2. The vaccine candidate consisted of the self-assembling 60-subunit I3-01 protein scaffold covalently decorated with the SARS-CoV-2 receptor-binding domain (RBD) using the SpyCatcher-SpyTag system. We verified the intended antigen display features by reconstructing the I3-01 scaffold to 3.4 A using cryogenicelectron microscopy. Using this RBD-grafted SpyCage scaffold (RBD + SpyCage), we performed two intranasal vaccination studies in the "gold-standard" pre-clinical Syrian hamster model. The initial study focused on assessing the immunogenicity of RBD + SpyCage combined with the LTA1 intranasal adjuvant. These studies showed RBD + SpyCage vaccination induced an antibody response that promoted viral clearance but did not prevent infection. Inclusion of the LTA1 adjuvant enhanced the magnitude of the antibody response but did not enhance protection. Thus, in an expanded study, in the absence of an intranasal adjuvant, we evaluated if covalent bonding of RBD to the scaffold was required to induce an antibody response. Covalent grafting of RBD was required for the vaccine to be immunogenic, and animals vaccinated with RBD + SpyCage more rapidly cleared SARS-CoV-2 from both the upper and lower respiratory tract. These findings demonstrate the intranasal SpyCage vaccine platform can induce protection against SARS-CoV-2 and, with additional modifications to improve immunogenicity, is a versatile platform for the development of intranasal vaccines targeting respiratory pathogens.IMPORTANCEDespite the availability of efficacious COVID vaccines that reduce disease severity, SARS-CoV-2 continues to spread. To limit SARS-CoV-2 transmission, the next generation of vaccines must induce immunity in the mucosa of the upper respiratory tract. Therefore, we performed proof-of-principle, intranasal vaccination studies with a recombinant protein nanoparticle scaffold, SpyCage, decorated with the RBD of the S protein (SpyCage + RBD). We show that SpyCage + RBD was immunogenic and enhanced SARS-CoV-2 clearance from the nose and lungs of Syrian hamsters. Moreover, covalent grafting of the RBD to the scaffold was required to induce an immune response when given via the intranasal route. These proof-of-concept findings indicate that with further enhancements to immunogenicity (e.g., adjuvant incorporation and antigen optimization), the SpyCage scaffold has potential as a versatile, intranasal vaccine platform for respiratory pathogens.

Renal Dysfunction at Discharge and Long-Term Survival in Acute Type A Aortic Dissection.

INTRODUCTION: We aimed to investigate the association between renal dysfunction at discharge and long-term survival in acute type A aortic dissection (ATAAD) patients following surgery. METHODS: From 2000 to 2021, 784 patients underwent aortic repair for an ATAAD. Patients were stratified based on creatinine (Cr) level at discharge alive or dead: normal Cr (n = 582) and elevated Cr defined as >1.3 mg/dL for males and >1.0 mg/dL for females or on dialysis at discharge (n = 202). RESULTS: Preoperatively, both groups had similar rates of comorbidities except for the elevated-Cr group which had more diabetes, chronic obstructive pulmonary disease, and chronic and acute renal insufficiency. Both groups had similar open ATAAD repair procedures. Postoperative outcomes in the elevated-Cr group were significantly worse, including six times higher operative mortality (20% versus 3.4%, P < 0.0001). The landmark long-term survival after discharge alive was significantly worse in the elevated-Cr group than the normal-Cr group (10-y survival: 48% versus 69%, P = 0.0009). The elevated Cr on dialysis at discharge group had significantly worse five-year survival (40%) than the elevated Cr not on dialysis at discharge group (80%, P = 0.02) and the normal-Cr group (87%, P < 0.0001). Additionally, the elevated Cr not on dialysis had a worse five-year survival than the normal-Cr group (80% versus 87%, P = 0.02). Elevated Cr at discharge on dialysis was a significant risk factor for late mortality (hazard ratio = 4.22, 95% confidence interval: [2.07, 8.61], P < 0.0001). CONCLUSIONS: Renal dysfunction at discharge was associated with significantly decreased short-term and long-term survival following open ATAAD repair. Surgeons should aggressively prevent renal dysfunction, especially new-onset dialysis, at discharge as it is correlated with significantly worse short-term and long-term outcomes.

A Systematic Review of Mortality Associations in Patients who Develop Tracheoinnominate Artery Fistula Following Tracheostomy.

OBJECTIVE: Tracheoinnominate artery fistulas (TIFs) are a rare but deadly complication of tracheostomy. Tracheoinnominate artery fistula cases in the literature were summarized in order to understand mortality associations. METHODS: MEDLINE was searched for studies reporting individual characteristics of patients with TIFs after tracheostomy, excluding cases without tracheostomy or with additional procedures at the tracheostomy site. This study followed PRISMA guidelines. RESULTS: 121 TIF patients from 18 case series and 46 case reports were included. The median age was 40 years, and 52.9% were male. The overall mortality rate was 64.5%. There were differences in mortality between cases that presented initially with vs without sentinel bleeding (odds ratio [OR] .34; CI [confidence interval] .16-.73; P = .006). The mortality rate also differed in whether or not the tracheostomy cuff was over-inflated for temporary hemostasis during resuscitation (OR 3.57 (CI 1.57-8.09); P = .002). Treatment compared to no treatment had lower mortality rates (OR .11 (CI 0.04-.32); P < .001); no differences were found if treatment was endovascular vs open surgical. CONCLUSIONS: Mortality is a major concern after detection of a TIF and resuscitation paired with endovascular or open surgical intervention is imperative. Rapidly investigating sentinel bleeds and intervening upon hemorrhage with temporary cuff over inflation may lead to improved outcomes.

Intermittent cytomegalovirus infection alters neurobiological metabolism and induces cognitive deficits in mice.

Risk factors contributing to dementia are multifactorial. Accumulating evidence suggests a role for pathogens as risk factors, but data is largely correlative with few causal relationships. Here, we demonstrate that intermittent murine cytomegalovirus (MCMV) infection of mice, alters blood brain barrier (BBB) permeability and metabolic pathways. Increased basal mitochondrial function is observed in brain microvessels cells (BMV) exposed to intermittent MCMV infection and is accompanied by elevated levels of superoxide. Further, mice score lower in cognitive assays compared to age-matched controls who were never administered MCMV. Our data show that repeated systemic infection with MCMV, increases markers of neuroinflammation, alters mitochondrial function, increases markers of oxidative stress and impacts cognition. Together, this suggests that viral burden may be a risk factor for dementia. These observations provide possible mechanistic insights through which pathogens may contribute to the progression or exacerbation of dementia.

Passive antibody transfer from pregnant women to their fetus are maximized after SARS-CoV-2 vaccination irrespective of prior infection.

Background: Pregnancy is associated with a higher risk of adverse symptoms and outcomes for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection for both mother and neonate. Antibodies can provide protection against SARS-CoV-2 infection and are induced in pregnant women after vaccination or infection. Passive transfer of these antibodies from mother to fetus in utero may provide protection to the neonate against infection. However, it is unclear whether the magnitude or quality and kinetics of maternally derived fetal antibodies differs in the context of maternal infection or vaccination. Objective: We aimed to determine whether antibodies transferred from maternal to fetus differed in quality or quantity between infection- or vaccination-induced humoral immune responses. Methods: We evaluated 93 paired maternal and neonatal umbilical cord blood plasma samples collected between October 2020 and February 2022 from a birth cohort of pregnant women from New Orleans, Louisiana, with histories of SARS-CoV-2 infection and/or vaccination. Plasma was profiled for the levels of spike-specific antibodies and induction of antiviral humoral immune functions, including neutralization and Fc-mediated innate immune effector functions. Responses were compared between 4 groups according to maternal infection and vaccination. Results: We found that SARS-CoV-2 vaccination or infection during pregnancy increased the levels of antiviral antibodies compared to naive subjects. Vaccinated mothers and cord samples had the highest anti-spike antibody levels and antiviral function independent of the time of vaccination during pregnancy. Conclusions: These results show that the most effective passive transfer of functional antibodies against SARS-CoV-2 in utero is achieved through vaccination, highlighting the importance of vaccination in pregnant women.