Metabolomic profiling identifies novel metabolites associated with cardiac dysfunction.

Metabolic comorbidities, such as obesity and diabetes, are associated with subclinical alterations in both cardiac structure/function and natriuretic peptides prior to the onset of heart failure (HF). Despite this, the exact metabolic pathways of cardiac dysfunction which precede HF are not well-defined. Among older individuals without HF in the Multi-Ethnic Study of Atherosclerosis (MESA), we evaluated the associations of 47 circulating metabolites measured by 1H-NMR with echocardiographic measures of cardiac structure and function. We then evaluated associations of significant metabolites with circulating N-terminal pro-B-type natriuretic peptide (NT-proBNP). In a separate cohort, we evaluated differences between top metabolites in patients with HF with preserved ejection fraction (HFpEF) and comorbidity-matched controls. Genetic variants associated with top metabolites (mQTLs) were then related to echocardiographic measures and NT-proBNP. Among 3440 individuals with metabolic and echocardiographic data in MESA (62 ± 10 years, 52% female, 38% White), 10 metabolites broadly reflective of glucose and amino acid metabolism were associated with at least 1 measure of cardiac structure or function. Of these 10 metabolites, 4 (myo-inositol, glucose, dimethylsulfone, carnitine) were associated with higher NT-proBNP and 2 (d-mannose, acetone) were associated with lower NT-proBNP. In a separate cohort, patients with HFpEF had higher circulating myo-inositol levels compared with comorbidity-matched controls. Genetic analyses revealed that 1 of 6 known myo-inositol mQTLs conferred risk of higher NT-proBNP. In conclusion, metabolomic profiling identifies several novel metabolites associated with cardiac dysfunction in a cohort at high risk for HF, revealing pathways potentially relevant to future HF risk.

Association between high-density mapping of atypical atrial flutter, clinical outcomes and healthcare utilization.

BACKGROUND: Success of atypical atrial flutter (AAFL) ablation has historically been limited by difficulty mapping the complex re-entrant circuits involved. While high-density (HD) mapping has become commonplace in clinical practice, there are limited data on outcomes of HD versus non-HD mapping for AAFL ablation. OBJECTIVE: To compare clinical outcomes and healthcare utilization using HD mapping versus non-HD mapping for AAFL ablation. METHODS: Retrospective analysis of all AAFL procedures between 2005 and 2022 at an academic medical center was conducted. Procedures utilizing a 16-electrode HD Grid catheter and Precision mapping system were compared to procedures using prior generation 10-20 electrode spiral catheters and the Velocity system (Abbott, IL). Cox regression models and Poisson regression models were utilized to examine procedural and healthcare utilization outcomes. Models were adjusted for left ventricular ejection fraction, CHA2DS2-VASc, and history of prior ablation. RESULTS: There were 108 patients (62% HD mapping) included in the analysis. Baseline clinical characteristics were similar between groups. Use of HD mapping was associated with a higher rate of AAFL circuit delineation (92.5% vs. 76%; p = .014) and a greater adjusted procedure success rate, defined as non-inducibility at procedure end, (aRR (95% CI) 1.26 (1.02-1.55) p = .035) than non-HD mapping. HD mapping was also associated with a lower rate of ED visits (aIRR (95% CI) 0.32 (0.14-0.71); p = .007) and hospitalizations (aIRR (95% CI) 0.32 (0.14-0.68); p = .004) for AF/AFL/HF through 1 year. While there was a lower rate of recurrent AFL through 1 year among HD mapping cases (aHR (95% CI) 0.60 (0.31-1.16) p = .13), statistical significance was not met likely due to the low sample size and higher rate of ambulatory rhythm monitoring in the HD group (61% vs. 39%, p = .025). CONCLUSION: Compared to non-HD mapping, AAFL ablation with HD mapping is associated with improvements in the ability to define the AAFL circuit, greater procedural success, and a reduction in the number of ED visits and hospitalization for AF/AFL/HF.

The Association of Intravitreal Anti-VEGF Injections With Kidney Function in Diabetic Retinopathy.

Purpose: To examine whether patients with diabetic retinopathy receiving intravitreal anti-VEGF injections are at increased risk of kidney function decline. Design: Retrospective cohort study. Participants: Included 187 patients who received intravitreal anti-VEGF injections for proliferative diabetic retinopathy (PDR) and/or diabetic macular edema (DME), and 929 controls with non-PDR who did not receive injections, at a large tertiary care center in Chicago, Illinois. Methods: We queried our institutional enterprise data warehouse to identify patients with diabetic retinopathy, determined whether they received intravitreal anti-VEGF injections, and followed kidney function for all patients over time. Main Outcome Measures: We assessed time to sustained 40% decline in estimated glomerular filtration rate (eGFR) from baseline in patients receiving intravitreal anti-VEGF injections and compared it with controls using Kaplan-Meier and multivariable adjusted Cox proportional hazards regression models. Results: This study included 1116 patients (565 female [50.6%]; mean [standard deviation {SD}] age, 57.3 [13.6] years; mean [SD] eGFR, 65.3 [32.1] ml/min/1.73 m2). Of these, 187 patients received ≥ 1 intravitreal anti-VEGF injection (mean [SD], 11.4 [13.1] injections) for PDR and/or DME, and 929 controls with non-PDR received no injections. Intravitreal anti-VEGF injection use was not associated with an increased risk of kidney function decline (hazard ratio [HR], 1.44; 95% confidence interval [CI], 0.97-2.15). Subgroup analyses revealed that use of intravitreal anti-VEGF injections was associated with increased risk of kidney function decline in male patients (HR, 1.87; 95% CI, 1.11-3.14) but not female patients (HR, 0.97; 95% CI, 0.50-1.89). Intravitreal anti-VEGF injection use was also associated with an increased risk of kidney function decline in patients with baseline eGFR > 30 ml/min/1.73 m2 (HR, 1.86; 95% CI, 1.15-3.01), but not in individuals with baseline eGFR ≤ 30 ml/min/1.73 m2 (HR, 0.97; 95% CI, 0.45-2.10). Among patients who received injections, receiving ≥ 12 injections was not associated with risk of kidney function decline (HR, 1.13; 95% CI, 0.52-2.49). Conclusions: Intravitreal anti-VEGF injections for patients with diabetic retinopathy are overall well-tolerated with respect to kidney function, but the use of intravitreal anti-VEGF injections was associated with an increased risk of kidney function decline in certain subgroups of patients. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Rural-Urban Disparities in Adverse Maternal Outcomes in the United States, 2016-2019.

Objectives. To describe differences in maternal admissions to the intensive care unit (ICU) and mortality in rural versus urban areas in the United States. Methods. We performed a nationwide analysis and calculated age-standardized rates and rate ratios (RRs) of maternal ICU admission and mortality per 100 000 live births between 2016 and 2019 in rural versus urban areas. Results. From 2016 to 2019, there was no significant increase in age-standardized rates of maternal ICU admissions in rural (170.6-192.3) or urban (161.7-172.4) areas, with a significantly higher rate, albeit a relatively small difference, in rural versus urban areas (2019 RR = 1.14; 95% confidence interval [CI] = 1.04, 1.20). Maternal mortality increased in both rural (66.9-81.7 deaths per 100 000 live births) and urban (38.1-42.3) areas and was nearly 2 times higher in rural areas (2019 RR = 1.93; 95% CI = 1.71, 2.17). Conclusions. Pregnant individuals in rural areas are at higher risk for ICU admission and mortality than are their urban counterparts. Significant increases in maternal mortality occurred in rural and urban areas. Public Health Implications. Public health efforts need to focus on resource-limited rural areas to mitigate geographic disparities in maternal morbidity and mortality. (Am J Public Health. 2023;113(2): 224-227.https://doi.org/10.2105/AJPH.2022.307134).

The Interplay Between Policy and COVID-19 Outbreaks in South Asia: Longitudinal Trend Analysis of Surveillance Data.

BACKGROUND: COVID-19 transmission rates in South Asia initially were under control when governments implemented health policies aimed at controlling the pandemic such as quarantines, travel bans, and border, business, and school closures. Governments have since relaxed public health restrictions, which resulted in significant outbreaks, shifting the global epicenter of COVID-19 to India. Ongoing systematic public health surveillance of the COVID-19 pandemic is needed to inform disease prevention policy to re-establish control over the pandemic within South Asia. OBJECTIVE: This study aimed to inform public health leaders about the state of the COVID-19 pandemic, how South Asia displays differences within and among countries and other global regions, and where immediate action is needed to control the outbreaks. METHODS: We extracted COVID-19 data spanning 62 days from public health registries and calculated traditional and enhanced surveillance metrics. We use an empirical difference equation to measure the daily number of cases in South Asia as a function of the prior number of cases, the level of testing, and weekly shifts in variables with a dynamic panel model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R. RESULTS: Traditional surveillance metrics indicate that South Asian countries have an alarming outbreak, with India leading the region with 310,310 new daily cases in accordance with the 7-day moving average. Enhanced surveillance indicates that while Pakistan and Bangladesh still have a high daily number of new COVID-19 cases (n=4819 and n=3878, respectively), their speed of new infections declined from April 12-25, 2021, from 2.28 to 2.18 and 3.15 to 2.35 daily new infections per 100,000 population, respectively, which suggests that their outbreaks are decreasing and that these countries are headed in the right direction. In contrast, India's speed of new infections per 100,000 population increased by 52% during the same period from 14.79 to 22.49 new cases per day per 100,000 population, which constitutes an increased outbreak. CONCLUSIONS: Relaxation of public health restrictions and the spread of novel variants fueled the second wave of the COVID-19 pandemic in South Asia. Public health surveillance indicates that shifts in policy and the spread of new variants correlate with a drastic expansion in the pandemic, requiring immediate action to mitigate the spread of COVID-19. Surveillance is needed to inform leaders whether policies help control the pandemic.

Surveillance of the Second Wave of COVID-19 in Europe: Longitudinal Trend Analyses.

BACKGROUND: The COVID-19 pandemic has severely impacted Europe, resulting in a high caseload and deaths that varied by country. The second wave of the COVID-19 pandemic has breached the borders of Europe. Public health surveillance is necessary to inform policy and guide leaders. OBJECTIVE: This study aimed to provide advanced surveillance metrics for COVID-19 transmission that account for weekly shifts in the pandemic, speed, acceleration, jerk, and persistence, to better understand countries at risk for explosive growth and those that are managing the pandemic effectively. METHODS: We performed a longitudinal trend analysis and extracted 62 days of COVID-19 data from public health registries. We used an empirical difference equation to measure the daily number of cases in Europe as a function of the prior number of cases, the level of testing, and weekly shift variables based on a dynamic panel model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R. RESULTS: New COVID-19 cases slightly decreased from 158,741 (week 1, January 4-10, 2021) to 152,064 (week 2, January 11-17, 2021), and cumulative cases increased from 22,507,271 (week 1) to 23,890,761 (week 2), with a weekly increase of 1,383,490 between January 10 and January 17. France, Germany, Italy, Spain, and the United Kingdom had the largest 7-day moving averages for new cases during week 1. During week 2, the 7-day moving average for France and Spain increased. From week 1 to week 2, the speed decreased (37.72 to 33.02 per 100,000), acceleration decreased (0.39 to -0.16 per 100,000), and jerk increased (-1.30 to 1.37 per 100,000). CONCLUSIONS: The United Kingdom, Spain, and Portugal, in particular, are at risk for a rapid expansion in COVID-19 transmission. An examination of the European region suggests that there was a decrease in the COVID-19 caseload between January 4 and January 17, 2021. Unfortunately, the rates of jerk, which were negative for Europe at the beginning of the month, reversed course and became positive, despite decreases in speed and acceleration. Finally, the 7-day persistence rate was higher during week 2 than during week 1. These measures indicate that the second wave of the pandemic may be subsiding, but some countries remain at risk for new outbreaks and increased transmission in the absence of rapid policy responses.

Dynamic Public Health Surveillance to Track and Mitigate the US COVID-19 Epidemic: Longitudinal Trend Analysis Study.

BACKGROUND: The emergence of SARS-CoV-2, the virus that causes COVID-19, has led to a global pandemic. The United States has been severely affected, accounting for the most COVID-19 cases and deaths worldwide. Without a coordinated national public health plan informed by surveillance with actionable metrics, the United States has been ineffective at preventing and mitigating the escalating COVID-19 pandemic. Existing surveillance has incomplete ascertainment and is limited by the use of standard surveillance metrics. Although many COVID-19 data sources track infection rates, informing prevention requires capturing the relevant dynamics of the pandemic. OBJECTIVE: The aim of this study is to develop dynamic metrics for public health surveillance that can inform worldwide COVID-19 prevention efforts. Advanced surveillance techniques are essential to inform public health decision making and to identify where and when corrective action is required to prevent outbreaks. METHODS: Using a longitudinal trend analysis study design, we extracted COVID-19 data from global public health registries. We used an empirical difference equation to measure daily case numbers for our use case in 50 US states and the District of Colombia as a function of the prior number of cases, the level of testing, and weekly shift variables based on a dynamic panel model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R. RESULTS: Examination of the United States and state data demonstrated that most US states are experiencing outbreaks as measured by these new metrics of speed, acceleration, jerk, and persistence. Larger US states have high COVID-19 caseloads as a function of population size, density, and deficits in adherence to public health guidelines early in the epidemic, and other states have alarming rates of speed, acceleration, jerk, and 7-day persistence in novel infections. North and South Dakota have had the highest rates of COVID-19 transmission combined with positive acceleration, jerk, and 7-day persistence. Wisconsin and Illinois also have alarming indicators and already lead the nation in daily new COVID-19 infections. As the United States enters its third wave of COVID-19, all 50 states and the District of Colombia have positive rates of speed between 7.58 (Hawaii) and 175.01 (North Dakota), and persistence, ranging from 4.44 (Vermont) to 195.35 (North Dakota) new infections per 100,000 people. CONCLUSIONS: Standard surveillance techniques such as daily and cumulative infections and deaths are helpful but only provide a static view of what has already occurred in the pandemic and are less helpful in prevention. Public health policy that is informed by dynamic surveillance can shift the country from reacting to COVID-19 transmissions to being proactive and taking corrective action when indicators of speed, acceleration, jerk, and persistence remain positive week over week. Implicit within our dynamic surveillance is an early warning system that indicates when there is problematic growth in COVID-19 transmissions as well as signals when growth will become explosive without action. A public health approach that focuses on prevention can prevent major outbreaks in addition to endorsing effective public health policies. Moreover, subnational analyses on the dynamics of the pandemic allow us to zero in on where transmissions are increasing, meaning corrective action can be applied with precision in problematic areas. Dynamic public health surveillance can inform specific geographies where quarantines are necessary while preserving the economy in other US areas.

Deep Vein Thrombosis Due to Fecal Impaction.

BACKGROUND: Deep vein thrombosis (DVT) can occasionally be secondary to mechanical compressions, such as in May-Thurner syndrome. To our knowledge, no cases of DVT associated with mechanical compression by fecal impaction in a pediatric patient have been previously reported. CASE PRESENTATION: An 18-year-old developmentally delayed female presented to the emergency department with swelling involving her left lower extremity. Cross-sectional imaging revealed a significant stool burden in the rectosigmoid colon compressing the left external iliac vein and causing secondary thrombosis. Thrombectomy successfully alleviated the clot burden. CONCLUSION: This case underscores the potentially serious implications of severe fecal impaction in the pediatric and adolescent populations.