Aortic Dissection During Pregnancy and Puerperium: Contemporary Incidence and Outcomes in the United States.

Background Aortic dissection (AD) during pregnancy and puerperium is a rare catastrophe with devastating consequences for both parent and fetus. Population-level incidence trends and outcomes remain relatively undetermined. Methods and Results We queried a US population-based health care database, the National Inpatient Sample, and identified all patients with a pregnancy-related AD hospitalization from 2002 to 2017. In total, 472 pregnancy-related AD hospitalizations (mean age, 30.9±0.6 years) were identified from 68 514 000 pregnancy-related hospitalizations (0.69 per 100 000 pregnancy-related hospitalizations), with 107 (22.7%) being type A and 365 (77.3%) being type B. The incidence of AD appeared to increase over the 16-year study period but was not statistically significant (P for trend >0.05). Marfan syndrome, primary hypertension, and preeclampsia/eclampsia were found in 21.9%, 14.4%, and 11.5%, respectively. On multivariable logistic regression analysis, Marfan syndrome was associated with the highest risk of developing AD during pregnancy and puerperium (adjusted odds ratio, 3469.36 [95% CI, 1767.84-6831.75]; P<0.001). The in-hospital mortalities of AD, type A AD, and type B AD were 7.3%, 4.3%, and 8.1%, respectively. Length of hospital stay for the AD, type A AD, and type B AD groups were 7.7±0.8, 10.4±1.9, and 6.9±0.9 days, respectively. Conclusions We quantified population-level incidence and in-hospital mortality in the United States and observed an increase in the incidence of pregnancy-related AD. In contrast, its in-hospital mortality appears lower than that of non-pregnancy-related AD.

Association of Intravenous Drug Use and Length of Stay Following Infective Endocarditis.

INTRODUCTION: Intravenous drug use (IVDU) and associated infective endocarditis (IE) has been on the rise in the US since the beginning of the opioid epidemic. IVDU-IE has high morbidity and mortality, and treatment can be lengthy. We aim to quantify the association between IVDU and length of stay (LOS) in IE patients. METHODS: The National Inpatient Sample database was used to identify IE patients, which was then stratified into IVDU-IE and non-IVDU-IE groups. Weighted values of hospitalizations were used to generate national estimates. Multivariable linear and logistic regression analyses were applied to estimate the effects of IVDU on LOS. RESULTS: We identified 1,114,257 adult IE patients, among which 123,409 (11.1%) were IVDU-IE. Compared to non-IVDU-IE patients, IVDU-IE patients were younger, had fewer comorbidities, and had an overall longer LOS (median [interquartile range]: 10 [5-20] versus 7 [4-13] d, P < 0.001), with a greater percentage of patients with a LOS longer than 30 d (13.7% versus 5.7%, P < 0.001). After adjusting for multiple demographic and clinical factors, IVDU was independently associated with a 1.25-d increase in LOS (beta-coefficient = 1.25, 95% confidence interval [CI]: 0.95-1.54, P < 0.001) and 35% higher odds of being hospitalized for more than 30 d (odds ratio = 1.35, 95% CI: 1.27-1.44, P < 0.001). CONCLUSIONS: Among IE patients, being IVDU has associated with a longer LOS and a higher risk of prolonged hospital stay. Steps toward the prevention of IE in the IVDU population should be taken to avoid an undue burden on the healthcare system.

Estimating typhoid incidence from community-based serosurveys: a multicohort study.

BACKGROUND: The incidence of enteric fever, an invasive bacterial infection caused by typhoidal Salmonellae (Salmonella enterica serovars Typhi and Paratyphi), is largely unknown in regions without blood culture surveillance. The aim of this study was to evaluate whether new diagnostic serological markers for typhoidal Salmonella can reliably estimate population-level incidence. METHODS: We collected longitudinal blood samples from patients with blood culture-confirmed enteric fever enrolled from surveillance studies in Bangladesh, Nepal, Pakistan, and Ghana between 2016 and 2021 and conducted cross-sectional serosurveys in the catchment areas of each surveillance site. We used ELISAs to measure quantitative IgA and IgG antibody responses to hemolysin E and S Typhi lipopolysaccharide. We used Bayesian hierarchical models to fit two-phase power-function decay models to the longitudinal antibody responses among enteric fever cases and used the joint distributions of the peak antibody titres and decay rate to estimate population-level incidence rates from cross-sectional serosurveys. FINDINGS: The longitudinal antibody kinetics for all antigen-isotypes were similar across countries and did not vary by clinical severity. The seroincidence of typhoidal Salmonella infection among children younger than 5 years ranged between 58·5 per 100 person-years (95% CI 42·1-81·4) in Dhaka, Bangladesh, to 6·6 per 100 person-years (4·3-9·9) in Kavrepalanchok, Nepal, and followed the same rank order as clinical incidence estimates. INTERPRETATION: The approach described here has the potential to expand the geographical scope of typhoidal Salmonella surveillance and generate incidence estimates that are comparable across geographical regions and time. FUNDING: Bill & Melinda Gates Foundation. TRANSLATIONS: For the Nepali, Bengali and Urdu translations of the abstract see Supplementary Materials section.

The effect of a statewide prescription drug monitoring program on opioid prescribing patterns.

PURPOSE: Determine whether opioid prescribing patterns have changed as a result of implementation of a prescription drug monitoring program (PDMP) in the state of Massachusetts. MATERIALS AND METHODS: A multicentered retrospective study was performed including patients who received tonsillectomy, parotidectomy, thyroidectomy or direct laryngoscopy and biopsy with or without rigid esophagoscopy and/or rigid bronchoscopy at Lahey Hospital and Medical Center (Burlington, MA) or Boston Medical Center (Boston, MA). Opioid prescribing patterns were compared for the 12 months prior to implementation of the Massachusetts Prescription Awareness Tool (MassPAT) to 36 months of prescribing patterns post implementation. Quantity of opioids prescribed was based on morphine milligram equivalents (MME). Continuous variables were compared using analysis of variance (ANOVA) while categorical variables were compared using chi-squared test or Fisher's exact test. Multivariate analysis was performed using linear regression. RESULTS: A total of 2281 patients were included in the study. There was a significant association in mean overall MME prescribed comparing pre-MassPAT and post-MassPAT data [tonsillectomy: 635.9 ± 175.6 vs 463.3 ± 177.7 (p < 0.0001), parotidectomy: 250.4 ± 71.33 vs 169.8 ± 79.26 (p < 0.0001), thyroidectomy: 186.2 ± 81.14 vs 118.3 ± 88.79 (p < 0.0001), direct laryngoscopy with biopsy: 308.3 ± 246.9 vs 308.3 ± 246.9 (p = 0.0201)]. There was also a significant association between length of opioid prescription (days) and implementation of MassPAT, but there was no significant difference in the percent of patients requiring refills pre- MassPAT and post-MassPAT. CONCLUSION: This study demonstrates that prescribers have been able to significantly decrease the amount of opioids prescribed for tonsillectomy, parotidectomy, thyroidectomy, and direct laryngoscopy and biopsy and patients have not required additional opioid refills.

Reproducibility and Repeatability of Assessment of Myocardial Light Chain Amyloidosis Burden Using 18F-Florbetapir PET/CT.

BACKGROUND: 18F-florbetapir PET is emerging as an excellent quantitative tool to quantify cardiac light chain (AL) amyloidosis burden. The primary aim of this study was to determine interobserver reproducibility and intraobserver repeatability, defined per the recommendations of the Quantitative Imaging Biomarker Alliance technical performance group, of PET 18F-florbetapir retention index (RI) in patients with cardiac AL amyloidosis. METHODS: The study cohort comprised 37 subjects with systemic AL amyloidosis enrolled in the prospective study: Molecular Imaging of Primary Amyloid Cardiomyopathy (clinical trials.gov NCT: 02641145). Using 10 mCi of 18F-florbetapir, a 60-minute dynamic cardiac scan was acquired. Global and segmental left ventricular estimates of retention index (RI) of 18F-florbetapir were calculated (Carimas 2.9 software, Turku, Finland). RI was analyzed twice, at least 24 hours apart, by two independent observers. Intraobserver repeatability and interobserver reproducibility were evaluated using Bland-Altman plots and scatter plots with fitted linear regression curves. RESULTS: All reproducibility (interobserver, r = 0.98) and repeatability (intraobserver, R=0.99 for each observer) measures of 18F-florbetapir RI are excellent. On the Bland-Altman plots, the agreement limits for global 18F-florbetapir RI were high and ranged for reproducibility (interobserver) from - 9.3 to + 9.4% (Fig. 1), and for repeatability (observer 1 from - 10.8 to + 10.7% and from - 9.2 to + 11.4%, for observer 2). CONCLUSIONS: The present study showed excellent interobserver reproducibility and intraobserver repeatability of 18F-florbetapir PET retention index in patients with cardiac AL amyloidosis.

Persistence and decay of human antibody responses to the receptor binding domain of SARS-CoV-2 spike protein in COVID-19 patients.

We measured plasma and/or serum antibody responses to the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2 in 343 North American patients infected with SARS-CoV-2 (of which 93% required hospitalization) up to 122 days after symptom onset and compared them to responses in 1548 individuals whose blood samples were obtained prior to the pandemic. After setting seropositivity thresholds for perfect specificity (100%), we estimated sensitivities of 95% for IgG, 90% for IgA, and 81% for IgM for detecting infected individuals between 15 and 28 days after symptom onset. While the median time to seroconversion was nearly 12 days across all three isotypes tested, IgA and IgM antibodies against RBD were short-lived with median times to seroreversion of 71 and 49 days after symptom onset. In contrast, anti-RBD IgG responses decayed slowly through 90 days with only 3 seropositive individuals seroreverting within this time period. IgG antibodies to SARS-CoV-2 RBD were strongly correlated with anti-S neutralizing antibody titers, which demonstrated little to no decrease over 75 days since symptom onset. We observed no cross-reactivity of the SARS-CoV-2 RBD-targeted antibodies with other widely circulating coronaviruses (HKU1, 229 E, OC43, NL63). These data suggest that RBD-targeted antibodies are excellent markers of previous and recent infection, that differential isotype measurements can help distinguish between recent and older infections, and that IgG responses persist over the first few months after infection and are highly correlated with neutralizing antibodies.

Dynamics and significance of the antibody response to SARS-CoV-2 infection.

BACKGROUND: Characterizing the humoral immune response to SARS-CoV-2 and developing accurate serologic assays are needed for diagnostic purposes and estimating population-level seroprevalence. METHODS: We measured the kinetics of early antibody responses to the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2 in a cohort of 259 symptomatic North American patients infected with SARS-CoV-2 (up to 75 days after symptom onset) compared to antibody levels in 1548 individuals whose blood samples were obtained prior to the pandemic. RESULTS: Between 14-28 days from onset of symptoms, IgG, IgA, or IgM antibody responses to RBD were all accurate in identifying recently infected individuals, with 100% specificity and a sensitivity of 97%, 91%, and 81% respectively. Although the estimated median time to becoming seropositive was similar across isotypes, IgA and IgM antibodies against RBD were short-lived with most individuals estimated to become seronegative again by 51 and 47 days after symptom onset, respectively. IgG antibodies against RBD lasted longer and persisted through 75 days post-symptoms. IgG antibodies to SARS-CoV-2 RBD were highly correlated with neutralizing antibodies targeting the S protein. No cross-reactivity of the SARS-CoV-2 RBD-targeted antibodies was observed with several known circulating coronaviruses, HKU1, OC 229 E, OC43, and NL63. CONCLUSIONS: Among symptomatic SARS-CoV-2 cases, RBD-targeted antibodies can be indicative of previous and recent infection. IgG antibodies are correlated with neutralizing antibodies and are possibly a correlate of protective immunity.

Evaluation of a Rapid Point-of-Care Multiplex Immunochromatographic Assay for the Diagnosis of Enteric Fever.

There is a critical need for an improved rapid diagnostic for enteric fever. We have previously demonstrated that serum IgA responses targeting Salmonella enterica serovar Typhi hemolysin E (HlyE) and lipopolysaccharide (LPS) are able to discriminate patients with acute typhoid from healthy controls in areas where enteric fever is endemic (healthy endemic controls) and from patients with other bacterial infections. We now have data demonstrating that IgA antibody responses against these antigens also work well for identifying patients with acute S. Paratyphi A infection. To develop a test for acute enteric fever detection, we have adapted a point-of-care immunochromatographic dual-path platform technology (DPP), which improves on the traditional lateral flow technology by using separate sample and conjugate paths and a compact, portable reader, resulting in diagnostics with higher sensitivity and multiplexing abilities. In this analysis, we have compared our standard enzyme-linked immunosorbent assay (ELISA) method to the DPP method in detecting acute phase plasma/serum anti-HlyE and anti-LPS IgA antibodies in a cohort of patients with culture-confirmed S. Typhi (n = 30) and Paratyphi A infection (n = 20), healthy endemic controls (n = 25), and febrile endemic controls (n = 25). We found that the DPP measurements highly correlated with ELISA results, and both antigens had an area under the curve (AUC) of 0.98 (sensitivity of 92%, specificity of 94%) with all controls and an AUC of 0.98 (sensitivity of 90%, specificity of 96%) with febrile endemic controls. Our results suggest that the point-of-care DPP Typhoid System has high diagnostic accuracy for the rapid detection of enteric fever and warrants further evaluation.IMPORTANCE Enteric fever remains a significant global problem, and control programs are significantly limited by the lack of an optimal assay for identifying individuals with acute infection. This is especially critical considering the recently released World Health Organization (WHO) position paper endorsing the role of the typhoid conjugate vaccine in communities where enteric fever is endemic. A reliable diagnostic test is needed to assess and evaluate typhoid intervention strategies and determine which high-burden areas may benefit most from a vaccine intervention. Our collaborative team has developed and evaluated a point-of-care serodiagnostic assay based on detection of anti-HlyE and LPS IgA. Our finding of the high diagnostic accuracy of the DPP Typhoid System for the rapid detection of enteric fever has the potential to have significant public health impact by allowing for improved surveillance and for control and prevention programs in areas with limited laboratory capacity.

Association between Nonalcoholic Fatty Liver Disease at CT and Coronary Microvascular Dysfunction at Myocardial Perfusion PET/CT.

Background Cardiovascular disease is a major cause of mortality in patients with nonalcoholic fatty liver disease (NAFLD). However, the association of NAFLD with coronary microvascular dysfunction is, to our knowledge, unknown. Purpose To determine whether coronary microvascular dysfunction is more prevalent in patients with NAFLD and to determine whether coronary microvascular dysfunction predicts major adverse cardiac events (MACE) independently of NAFLD. Materials and Methods This retrospective study (2006-2014) included patients without evidence of obstructive epicardial coronary artery disease and healthy left ventricular ejection fraction (≥40%) at a clinical rest and stress myocardial perfusion PET/CT. NAFLD was defined by a mean hepatic attenuation of less than 40 HU at CT and coronary microvascular dysfunction as a coronary flow reserve (CFR) of less than 2.0. A composite of all-cause mortality, myocardial infarction, coronary revascularization, and hospitalization because of heart failure comprised MACE (130 of 886 patients; 14.7%). The relation between NAFLD and MACE was assessed by using multivariable Cox regression analysis. Results Among 886 patients (mean age, 62 years ± 12 [standard deviation]; 631 women [mean age, 62 years ± 12 years] and 255 men [mean age, 61 years ± 12]; and ejection fraction, 63% ± 9), 125 patients (14.1%) had NAFLD and 411 patients (46.4%) had coronary microvascular dysfunction. Coronary microvascular dysfunction was more prevalent (64.8% vs 43.4%; P < .001) and CFR was lower (1.9 ± 1.1 vs 2.2 ± 0.7; P < .001) in patients with NAFLD compared with those without NAFLD. NAFLD independently predicted coronary microvascular dysfunction (P = .01). The interaction of NAFLD and male sex predicted MACE (hazard ratio, 1.45; 95% confidence interval: 1.08, 1.69; P = .008) and coronary microvascular dysfunction remained associated with MACE (adjusted hazard ratio, 1.46; 95% confidence interval: 1.02, 2.07; P = .04). Conclusion Coronary microvascular dysfunction was more prevalent in patients with nonalcoholic fatty liver disease and predicted major adverse cardiac events independently of nonalcoholic fatty liver disease. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Ambale-Venkatesh and Lima in this issue.

Readability of Spanish language online information for the initial treatment of burns.

OBJECTIVE: This study's aim is to identify the most popular online resources for burn treatment information available in the Spanish language, and to evaluate the readability of this information. METHODS: The phrase "tratamiento de quemaduras" (burn treatment) was entered into search engines Google and Bing on 9/15/2014 and 9/13/2017. The top 12 Spanish web results on each site were identified and analyzed using Readability Studio Professional Edition v2012.1. The software generated a "mean grade reading level" for each article, or the grade of students that could be expected to understand the article's language. RESULTS: 21 distinct articles were identified at T1 and 17 at T2, with seven overlapping between T1 and T2. The average grade reading level of all the websites ranged from 7.8 to 13.8 at T1 (approximately 8th grade to sophomore year of college) and 7.8 to 12.2 at T2. CONCLUSIONS: No websites were within 1 standard deviation of the American Medical Association recommended 6th grade reading level. With readability showing little improvement during the past three years, providers should be aware of the complexity of online literature, and the potential complications this presents to patients. Additionally, burn centers should prioritize generating more accessible information for the Spanish speaking public.