Premature ovarian insufficiency: a review on the role of tobacco smoke, its clinical harm, and treatment.

Premature ovarian insufficiency (POI) is a condition in which the quantity of follicles and the quality of oocytes gradually decrease. This results in an estrogen secretion disorder and abnormal follicle development, which can lead to related diseases, early onset of menopause, sexual dysfunction, and an increased risk of cardiovascular issues, osteoporosis, and depression, among others. This disease significantly impacts the physical and mental health and overall quality of life of affected women. Factors such as genetic abnormalities, oophorectomy, radiotherapy for malignancy, idiopathic conditions, and an unhealthy lifestyle, including smoking, can accelerate the depletion of the follicular pool and the onset of menopause. Extensive research has been conducted on the detrimental effects of tobacco smoke on the ovaries. This article aims to review the advancements in understanding the impact of tobacco smoke on POI, both in vivo and in vitro. Furthermore, we explore the potential adverse effects of common toxicants found in tobacco smoke, such as polycyclic aromatic hydrocarbons (PAHs), heavy metals like cadmium, alkaloids like nicotine and its major metabolite cotinine, benzo[a]pyrene, and aromatic amines. In addition to discussing the toxicants, this article also reviews the complications associated with POI and the current state of research and application of treatment methods. These findings will contribute to the development of more precise treatments for POI, offering theoretical support for enhancing the long-term quality of life for women affected by this condition.

The role of short-chain fatty acids produced by gut microbiota in the regulation of pre-eclampsia onset.

Background: Preeclampsia (PE) is a common pregnancy-related disorder characterized by disrupted maternal-fetal immune tolerance, involving diffuse inflammatory responses and vascular endothelial damage. Alterations in the gut microbiota (GM) during pregnancy can affect intestinal barrier function and immune balance. Aims and purpose: This comprehensive review aims to investigate the potential role of short-chain fatty acids (SCFAs), essential metabolites produced by the GM, in the development of PE. The purpose is to examine their impact on colonic peripheral regulatory T (Treg) cells, the pathogenic potential of antigen-specific helper T (Th) cells, and the inflammatory pathways associated with immune homeostasis. Key insights: An increasing body of evidence suggests that dysbiosis in the GM can lead to alterations in SCFA levels, which may significantly contribute to the development of PE. SCFAs enhance the number and function of colonic Treg cells, mitigate the pathogenic potential of GM-specific Th cells, and inhibit inflammatory progression, thereby maintaining immune homeostasis. These insights highlight the potential significance of GM dysregulation and SCFAs produced by GM in the pathogenesis of PE. While the exact causes of PE remain elusive, and definitive clinical treatments are lacking, the GM and SCFAs present promising avenues for future clinical applications related to PE, offering a novel approach for prophylaxis and therapy.

Expansion of Insurance Under the Affordable Care Act and Invasive Management of Acute Myocardial Infarction.

BACKGROUND: The Affordable Care Act of 2010 extended health insurance through expansion of Medicaid and subsidies for commercial insurance. Prior work has produced differing results in associating expanded insurance with improvements in health care processes and outcomes. Evaluating specific mechanisms of care processes and their association with insurance expansion may help reconcile those results. METHODS AND RESULTS: We used inpatient hospitalization data in the Nationwide Inpatient Sample (NIS) Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality from 1/1/2008 to 9/30/2015. We included all hospitalizations for acute myocardial infarction (AMI). As a primary outcome, we defined percent rate of AMI hospitalizations receiving percutaneous coronary intervention (PCI) per month. In the non-Medicare (intervention) group, there was a relative decrease of 0.2% of the monthly trend before and after expansion (95% CI [-0.3%, -0.1%]). In the Medicare group, there was a relative decrease of 0.1% of the monthly trend before and after expansion (95% CI [-0.2%, 0%]). CONCLUSIONS: We did not detect a relative difference in PCI for AMI associated with insurance expansion under health reform.

Development and validation of an echocardiographic algorithm to predict long-term mitral and tricuspid regurgitation progression.

AIMS: Prediction of mitral (MR) and tricuspid (TR) regurgitation progression on transthoracic echocardiography (TTE) is needed to personalize valvular surveillance intervals and prognostication. METHODS AND RESULTS: Structured TTE report data at Beth Israel Deaconess Medical Center, 26 January 2000-31 December 2017, were used to determine time to progression (≥1+ increase in severity). TTE predictors of progression were used to create a progression score, externally validated at Massachusetts General Hospital, 1 January 2002-31 December 2019. In the derivation sample (MR, N = 34 933; TR, N = 27 526), only 5379 (15.4%) individuals with MR and 3630 (13.2%) with TR had progression during a median interquartile range) 9.0 (4.1-13.4) years of follow-up. Despite wide inter-individual variability in progression rates, a score based solely on demographics and TTE variables identified individuals with a five- to six-fold higher rate of MR/TR progression over 10 years (high- vs. low-score tertile, rate of progression; MR 20.1% vs. 3.3%; TR 21.2% vs. 4.4%). Compared to those in the lowest score tertile, those in the highest tertile of progression had a four-fold increased risk of mortality. On external validation, the score demonstrated similar performance to other algorithms commonly in use. CONCLUSION: Four-fifths of individuals had no progression of MR or TR over two decades. Despite wide interindividual variability in progression rates, a score, based solely on TTE parameters, identified individuals with a five- to six-fold higher rate of MR/TR progression. Compared to the lowest tertile, individuals in the highest score tertile had a four-fold increased risk of mortality. Prediction of long-term MR/TR progression is not only feasible but prognostically important.

The Intersection of Type 2 Myocardial Infarction and Heart Failure.

Background Type 2 myocardial infarction (T2MI) is common and associated with high cardiovascular event rates. However, the relationship between T2MI and heart failure (HF) is uncertain. Methods and Results We identified patients with T2MI at a large tertiary hospital between October 2017 and May 2018. Patient characteristics, causes of T2MI, and subsequent HF hospitalizations were determined by physician chart review. We identified 359 patients with T2MI over the study period; 184 patients had a history of HF. Among patients with ejection fraction (EF) assessment (N=180), the majority had preserved EF (N=107; 59.4%), followed by reduced EF (N=54; 30.0%), and mid-range EF (N=19; 10.6%). Acute HF was the most common cause of T2MI (20.9%). Of those whose T2MI was precipitated by HF (N=75), the mean EF was 53.0±16.8% and 16 (21.3%) were de novo diagnoses of HF. Among patients with T2MI who were discharged alive with available follow-up (N=289), 5.5% were hospitalized with acute HF within 30 days, 17.3% within 180 days, and 22.1% within 1 year. In subgroup analyses, among patients with T2MI with prevalent or new HF (N=161), the rate of HF hospitalization at 1 year was 34.2%, considerably higher than those with T2MI and no HF diagnosis at discharge (7.0%; N=9/128). Conclusions Index presentations of HF or worsening chronic HF represent the most common causes of T2MI. ≈1 in 5 patients with T2MI will be readmitted for HF within 1 year of their event. Strategies to prevent HF events after a T2MI are needed.

Downstream Cascades of Care Following High-Sensitivity Troponin Test Implementation.

BACKGROUND: Patients with chest pain are often evaluated for acute myocardial infarction through troponin testing, which may prompt downstream services (cascades) of uncertain value. OBJECTIVES: This study sought to determine the association of high-sensitivity cardiac troponin (hs-cTn) assay implementation with cascade events. METHODS: Using electronic health record and billing data, this study examined patient-visits to 5 emergency departments from April 1, 2017, to April 1, 2019. Difference-in-differences analysis compared patient-visits for chest pain (n = 7,564) to patient-visits for other symptoms (n = 100,415) (irrespective of troponin testing) before and after hs-cTn assay implementation. Outcomes included presence of any cascade event potentially associated with an initial hs-cTn test (primary), individual cascade events, length of stay, and spending on cardiac services. RESULTS: Following hs-cTn implementation, patients with chest pain had a 2.8% (95% confidence interval [CI]: 0.72% to 4.9%) net increase in experiencing any cascade event. They were more likely to have multiple troponin tests (10.5%; 95% CI: 9.0% to 12.0%) and electrocardiograms (7.1 per 100 patient-visits; 95% CI: 1.8 to 12.4). However, they received net fewer computed tomography scans (-1.5 per 100 patient-visits; 95% CI: -1.8 to -1.1), stress tests (-5.9 per 100 patient-visits; 95% CI: -6.5 to -5.3), and percutaneous coronary intervention (PCI) (-0.65 per 100 patient-visits; 95% CI: -1.01 to -0.30) and were less likely to receive cardiac medications, undergo cardiology evaluation (-3.5%; 95% CI: -4.5% to 2.6%), or be hospitalized (-5.8%; 95% CI: -7.7% to -3.8%). Patients with chest pain had lower net mean length of stay (-0.24 days; 95% CI: -0.32 to -0.16) but no net change in spending. CONCLUSIONS: Hs-cTn assay implementation was associated with more net upfront tests yet fewer net stress tests, PCI, cardiology evaluations, and hospital admissions in patients with chest pain relative to patients with other symptoms.

Effect of Availability of Transcatheter Aortic-Valve Implantation on Survival for all Patients With Severe Aortic Stenosis.

Clinical outcomes for the overall severe aortic stenosis (AS) patient population are not well described because those medically managed are not included in procedural registries, and AS severity is not identifiable from administrative data. We aim to assess whether transcatheter aortic valve implantation (TAVI) availability has been associated with overall changes in survival for the whole AS patient population. This is important because patients with AS in real-world practice may differ from those included in randomized controlled trials, potentially attenuating the purported treatment efficacy estimated in trials. Classic severe AS patients (mean gradient ≥40 mmHg) were identified from an echocardiography database. Survival was defined as time since severe AS diagnosis until death. We first compared survival among all patients before and after TAVI availability in 2008. To further understand mechanism, we then assessed whether any survival changes were attributable to TAVI with extended Cox regression models comparing survival among TAVI, surgical aortic valve replacement, and medically managed patients. 3663 classic severe AS patients were included in the study. Median survival years for all patients were greater during the TAVI-era than Pre-TAVI-era (>11.5 vs 6.8, 5-year-HR = 0.8, time-varying effect p <0.0001), and increased median survival was greatest for patients age 65 to74 (>11.5 vs 9.5, 5-year-HR = 0.7, time-varying effect p = 0.045). TAVI patients age 65 to 74 had the lowest risk of death compared to medically managed patients (HR = 0.2, 95% CI = [0.1, 0.3], p <0.0001). In conclusion, in the TAVI-era, overall survival for patients with severe AS has doubled. This improvement is most marked for patients 65 to 74 years of age.

Early clinical and sociodemographic experience with patients hospitalized with COVID-19 at a large American healthcare system.

BACKGROUND: Despite over 4 million cases of novel coronavirus disease 2019 (COVID-19) in the United States, limited data exist including socioeconomic background and post-discharge outcomes for patients hospitalized with this disease. METHODS: In this case series, we identified patients with COVID-19 admitted to 3 Partners Healthcare hospitals in Boston, Massachusetts between March 7th, 2020, and March 30th, 2020. Patient characteristics, treatment strategies, and outcomes were determined. FINDINGS: A total of 247 patients hospitalized with COVID-19 were identified; the median age was 61 (interquartile range [IQR]: 50-76 years), 58% were men, 30% of Hispanic ethnicity, 21% enrolled in Medicaid, and 12% dual-enrolled Medicare/Medicaid. The median estimated household income was $66,701 [IQR: $50,336-$86,601]. Most patients were treated with hydroxychloroquine (72%), and statins (76%; newly initiated in 34%). During their admission, 103 patients (42%) required intensive care. At the end of the data collection period (June 24, 2020), 213 patients (86.2%) were discharged alive, 2 patients (0.8%) remain admitted, and 32 patients (13%) have died. Among those discharged alive (n = 213), 70 (32.9%) were discharged to a post-acute facility, 31 (14.6%) newly required supplemental oxygen, 19 (8.9%) newly required tube feeding, and 34 (16%) required new prescriptions for antipsychotics, benzodiazepines, methadone, or opioids. Over a median post-discharge follow-up of 80 days (IQR, 68-84), 22 patients (10.3%) were readmitted. INTERPRETATION: Patients hospitalized with COVID-19 are frequently of vulnerable socioeconomic status and often require intensive care. Patients who survive COVID-19 hospitalization have substantial need for post-acute services.

Home-Time After Discharge Among Patients With Type 2 Myocardial Infarction.

Background Home-time, defined as the time spent alive outside of a healthcare institution, has emerged as a patient-centered health outcome. The discharge locations and distribution of home-time after a type 2 myocardial infarction are unknown. Methods and Results Patients with a type 2 myocardial infarction between October 2017 and May 2018 at Massachusetts General Hospital were included. Patients discharged to hospice or without follow-up data were excluded. Our primary outcome was home-time defined as the number of days lived outside of a hospital, long-term acute care facility, skilled nursing facility, or rehabilitation facility. We identified 359 patients with type 2 myocardial infarction over the study period. Of those discharged alive (N=321), 62.9% were discharged home, and the remainder went to a facility or hospice. Among those with available follow-up data (N=289), the median home-time was 30 (interquartile range [IQR], 16-30) days at 30 days, 171 (IQR, 133-180) days at 180 days, and 347 (IQR, 203-362) days at 365 days. At 1 year, 29 patients (10%) with type 2 myocardial infarction had spent no time at home and only 57 patients (19.7%) spent the entire year alive and at home. At 1 year, postdischarge all-cause mortality was 23.2%, all-cause readmission was 69.2%, and major adverse cardiovascular events (composite of all-cause mortality, recurrent myocardial infarction, or stroke) was 34.9%. Home-time through 1 year correlated strongly with time-to-event all-cause mortality (τ=0.54, P<0.001) and major adverse cardiovascular events (τ=0.52, P<0.001) and modestly with a composite of all-cause mortality or readmission (τ=0.44, P<0.001). Conclusions Home-time is low after a hospitalization for type 2 myocardial infarction and correlates strongly with mortality and major adverse cardiovascular events.

Relationship of public health with continued shifting of party voting in the United States.

BACKGROUND: In the U.S. presidential election of 2016, communities with poorer public health shifted votes to the Republican party. Whether this trend has persisted beyond 2016 is unclear. METHODS: We created a county-level measure of public health (the "unhealthy" component) by performing principal component analysis on 9 health statistics. We then estimated shifting of votes by defining "net vote shift" as the percentage of Republican votes in the 2018 U.S. House of Representatives election minus the percentage of Republican votes in the same election in 2016. Finally, we performed linear regression to assess the independent, county-level association of the unhealthy component with net vote shift after adjusting for county-level demographic factors. RESULTS: The mean county-level net vote shift was -6.4 percentage points (SD 12.6 percentage points), consistent with a mean net vote shift toward the Democratic party. After adjustment for demographic covariates, the unhealthy score was associated with higher net vote shift (17.7 percentage points shift toward Republican per unit unhealthy, p = .0323). CONCLUSIONS: In the 2018 congressional elections, despite an overall shift toward the Democratic Party there is evidence of ongoing shifting of community voting in unhealthy communities toward the Republican party.