Left atrial function in patients with rheumatic mitral stenosis: addressing prognostic insights beyond atrial fibrillation prediction.

Aims: Rheumatic mitral stenosis (MS) frequently leads to impaired left atrial (LA) function because of pressure overload, highlighting the underlying atrial pathology. Two-dimensional speckle tracking echocardiography (2D-STE) offers early detection of LA dysfunction, potentially improving risk assessment in patients with MS. This study aims to evaluate the predictive value of LA function assessed by 2D-STE for clinical outcomes in patients with MS. Methods and results: Between 2011 and 2021, patients with MS underwent LA function assessment using 2D-STE, with focus on the reservoir phase (LASr). Atrial fibrillation (AF) development constituted the primary outcome, with death or valve replacement as the secondary outcome. Conditional inference trees were employed for analysis, validated through sample splitting. The study included 493 patients with MS (mean valve area 1.1 ± 0.4 cm2, 84% female). At baseline, 166 patients (34%) had AF, with 62 patients (19%) developing AF during follow-up. LASr emerged as the primary predictor for new-onset AF, with a threshold of 17.9%. Over a mean 3.8-year follow-up, 125 patients (25%) underwent mitral valve replacement, and 32 patients (6.5%) died. A decision tree analysis identified key predictors such as age, LASr, severity of tricuspid regurgitation (TR), net atrioventricular compliance (C n), and early percutaneous mitral valvuloplasty, especially in patients aged ≤49 years, where LASr, with a threshold of 12.8%, significantly predicted adverse outcomes. Conclusion: LASr emerged as a significant predictor of cardiovascular events in this MS cohort, validated through a decision tree analysis. Patients were stratified into low- or high-risk categories for adverse outcomes, taking into account LASr, age, TR severity, and C n.

Regeneration of combined severe periodontal defects and vertical ridge defects using recombinant human platelet-derived growth factor-BB: A case series.

Dental implants are a reliable treatment option for restoring missing teeth, but adequate bone quantity and quality are crucial for success. This case series presents four cases treated by different clinicians, all following very similar concepts for combined periodontal and vertical ridge augmentation using recombinant human platelet-derived growth factor-BB. All cases involved a severe periodontal defect requiring either extraction of the adjacent tooth or periodontal regeneration. Different bone grafts and membrane types were utilised. Although true periodontal regeneration cannot be said categorically to have occurred due to a lack of histological evidence, the clinical and radiographic findings suggest almost complete bone fill in all cases. This case series demonstrates that combined periodontal and vertical ridge augmentation using recombinant human platelet-derived growth factor-BB could be successful, but proper case selection and patient preparation for the possibility of multiple surgical procedures are recommended. Conflict-of-interest statement: At the time of preparing this manuscript, Dr Saleh was a clinical advisor for Lynch Biologics, Franklin, TN, USA. The other authors declare that they have no conflicts of interest relating to this study.

Ten-year prognostic outcomes of molar survival using the Miller-Mcentire Periodontal Prognostic Index - A longitudinal prospective study.

Background: A 10-year survival analysis was performed to assess the predictive validity of the periodontal risk score (formerly known as Miller-McEntire Periodontal Prognostic Index [MMPPI]) to predict long-term survival of periodontally diseased molars in a longitudinally assessed cohort. Materials and Methods: The MMPPI scores were computed at baseline by summarizing scores allocated for individual factors. The cohort was treated, followed up, and placed under regular periodontal maintenance. Molar survival data collected up to 10 years of follow-up were analyzed. Cox proportional regression was performed, and hazards ratio (HR) were computed for each prognostic factor and the MMPPI score. To estimate the predictive value of MMPPI, a receiver operating curve (ROC) curve analysis was performed. Results: From 1032 molars, 155 molars were extracted over the 10-year follow-up duration. Cox proportional hazard analysis showed significant hazard ratios for tooth loss for the component variables significant HR was noted for age: 4.92 (3.34:7.27), smoking: 1.74 (1.38-2.22), diabetes: 1.66 (1.49-1.86), molar type: 1.39 (1.15-1.67), probing depth: 2.00 (1.63-2.46), furcation: 2.64 (2.30-3.03), mobility: 3.45 (2.98-4.01), and total MMPPI score: 1.98 (1.85-2.12). ROC curve analysis showed an area under the curve value of 0.94 for the MMPPI index as a predictor of molar loss at 8 years, and the Youden index was maximized at the optimal cutoff point score of 7. Conclusions: All component scores of MMPPI showed significant hazard ratios at 10 years. These findings support the previous results from the 5-year analysis of this university-based cohort and warrant validation in independent cohorts.

Updated pathophysiological overview of functional MR (ventricular and atrial).

Basic mechanism of ventricular functional mitral regurgitation (FMR) is subvalvular tethering. Left ventricular (LV) dilatation, in association with mitral valve (MV) annular dilatation, causes outward displacement of papillary muscles (PMs), which abnormally pulls or tethers MV leaflets, resulting in MV tenting, reduction in leaflets coaptation and MR. Because surgical annuloplasty does shorten distance between anterior and posterior MV annuli to improve coaptation but does not address this subvalvular tethering, ventricular FMR frequently persists or recurs in the chronic stage after surgical annuloplasty. This high incidence of persistent/recurrent MR requires additional procedures to reduce subvalvular tethering. Although patients occasionally show marked improvements after annuloplasty with surgical tethering reduction procedures such as PM approximation, evidence to support benefits of such surgery is limited, requiring further trials. Recently, MV adaptation or MV leaflets tissue growth associated with LV dilatation attracts attention. Patients with larger MV leaflets with significant LV dilatation/dysfunction show less MV tethering and MR compared to those with smaller MV leaflets but with similar LV remodeling, suggesting the protective or beneficial role of MV leaflets tissue growth against LV remodeling. The MV leaflets tissue growth has the potential to lead to novel strategies of treatment for ventricular FMR. It is well known that atrial FMR is frequent in patients with left atrial dilatation, typically in those with isolated atrial fibrillation. The degree of atrial FMR is usually mild, even when it is present, and occasionally moderate, and severe atrial FMR is really rare. It is known that only severe regurgitation causes heart failure in primary MR, resulting in description on indications of surgery or intervention for only severe MR in current guidelines. Therefore, this atrial FMR up to moderate degree did not attract attention for a long time. However, recent studies have shown that patients with only moderate atrial FMR develop severe heart failure, suggesting more aggressive indication of MV surgery or intervention for "moderate" regurgitation in patients with atrial FMR. Therefore, atrial FMR is now recognized highly important. The unveiled malignant nature of atrial FMR arises many questions, including (1) why patients with only moderate atrial FMR develop heart failure? (2) do patients with mild atrial FMR develop heart failure or not?, and many others. Atrial FMR seems even more mysterious after the unveiling of its significance.

Electronic Vapor Products: Alarming Trends in United States Adolescents.

Background: The use of electronic vapor products (EVPs) increases the risks of nicotine addiction, drug-seeking behavior, mood disorders, and avoidable premature morbidities and mortality. We explored temporal trends in EVP use among US adolescents. Methods: We used data from the Youth Risk Behavior Survey for school grades 9 through 12 from 2015 (earliest available data) to 2021 (the most recently available data) from the US Centers for Disease Control and Prevention (n=57,006). Results: Daily use of EVPs increased from 2.0% in 2015 to 7.2% in 2019, a greater than 3.5-fold increase. Although the percentage decreased to 5.0% in 2021, it was still a >2.5-fold increase since 2015. In 2015, the percentage of EVP use was significantly higher in boys (2.8%) than girls (1.1%). By 2021, the percentage of EVP use was higher in girls (5.6%) than boys (4.5%), a 1.24-fold increase. In addition, the percentage of EVP use in 2021 was higher in White youth (6.5%) vs Black (3.1%), Asian (1.2%), and Hispanic/Latino (3.4%) youth compared to 2015, but White and Black adolescents had the highest increases of approximately 3.0-fold between 2015 and 2021. Adolescents in grade 12 had the highest percentages of EVP use at all periods. Conclusion: These data show alarming statistically significant and clinically important increases in EVP use in US adolescents in school grades 9 through 12. The magnitude of the increases may have been blunted by coronavirus disease 2019, a hypothesis that requires direct testing in analytic studies. These trends create clinical and public health challenges that require targeted interventions such as mass media campaigns and peer interventions to combat the influences of social norms that promote the adoption of risky health behaviors during adolescence.

Application of '10 Keys' Checklist and Partial Extraction Techniques to Optimize Esthetic Outcome for Adjacent Implants in the Esthetic Zone.

Placing immediate implants in the esthetic zone area poses significant challenges. Implants should be placed with consideration to hard and soft tissue management to optimize long term implant and cosmetic success. In this case report, two maxillary central incisors were extracted in two different time points, separated by 5 years because of horizontal root fractures. Implants were placed according to immediate single-tooth guidelines, using two different surgical and loading approaches, as risk assessment factors changed in the time between first immediate placement (#8) and second immediate placement (#9). These techniques included Partial Extraction Therapy (PET), the use of allograft and growth factors, connective tissue graft (CTG), platelet rich fibrin (PRF) and immediate and conventional loading. These were grouped as the '10 keys', a checklist used to pursue long term success. After 6-year and 1-year follow-up, radiographic and clinical results were satisfactory.

Increases in drug-related infant mortality in the United States.

OBJECTIVES: We explored temporal trends in drug-related infant deaths in the United States (U.S.) from 2018 to 2022. METHODS: We used data from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (WONDER). A total of 295 drug-involved infant deaths were identified from 2018 to 2022 (provisional mortality data for year 2022) based on the underlying cause of death. RESULTS: In the U.S. from 2018 to 2022, there was a significant 2.2-fold increase in drug-involved infant mortality. The observed increases were higher in non-Hispanic White and Black infants. The findings show that drug-involved infant deaths were more likely to occur in the postneonatal period, defined as ages 28-364 days (81.4 %) compared to the neonatal period. The most prevalent underlying causes of death included assault (homicide) by drugs, medicaments and biological substances (35.6 %) followed by poisoning due to exposure to narcotics and psychodysleptics (hallucinogens) (15.6 %). The most common multiple causes of drug-involved infant deaths were psychostimulants with abuse potential of synthetic narcotics. CONCLUSIONS: Drug-related infant mortality has increased significantly from 2018 to 2022. These increases are particularly evident among White and Black infants and occurred predominantly in the postneonatal period. These findings require more research but also indicate the need to address drug-involved infant deaths as preventable clinical and public health issues. Effective strategies to reduce drug-involved infant deaths will require preventing and treating maternal substance use disorders, enhancing prenatal care access, and addressing broader social and behavioral risk factors among vulnerable maternal and infant populations.

Ultrasound Performed by Emergency Physicians for Deep Vein Thrombosis: A Systematic Review.

Introduction: Point-of-care ultrasound (POCUS) performed by emergency physicians (EP) has emerged as an effective alternative to radiology department ultrasounds for the diagnosis of lower extremity deep vein thrombosis (DVT). Systematic reviews suggested good sensitivity and specificity overall for EP-performed POCUS for DVT diagnosis, yet high levels of heterogeneity were reported. Methods: In this systematic review and meta-analysis, we aimed to provide the most up-to-date estimates of the accuracy of EP-performed POCUS for diagnosis of DVT and to explore potential correlations with test performance. We performed systematic searches in MEDLINE and Embase for original, primary data articles from January 2012-June 2021 comparing the efficacy of POCUS performed by EPs to the local standard. Quality Assessment of Diagnostic Accuracy Studies-2 for individual articles are reported. We obtained summary measures of sensitivity, specificity, and their corresponding 95% confidence intervals (CI) using bivariate mixed-effects regression models. We performed meta-regression, subgroup, and sensitivity analyses as planned in the protocol CRD42021268799 submitted to PROSPERO. Results: Fifteen publications fit the inclusion criteria, totaling 2,511 examinations. Pooled sensitivity and specificity were 90% (95% CI 82%-95%) and 95% (CI 91%-97%), respectively. Subgroup analyses by EP experience found significantly better accuracy for exams performed by EP specialists (93%, CI 88%-97%) vs trainees (77%, CI 60%-94%). Specificity for EP specialists (97%, CI 94%-99%) was higher than for trainees (87%, CI 76%-99%, P = 0.01). Three-point compression ultrasound (CUS) was more sensitive than two-point CUS but was only statistically significant when limited to EP specialists (92% vs 88%, P = 0.07, and 95% vs 88%, P = 0.02, respectively). Conclusion: Point-of-care ultrasound performed by emergency physicians is sensitive and specific for the diagnosis of suspected DVT when performed by trained attending EPs. Three-point compression ultrasound examination may be more sensitive than two-point CUS.

Emerging data in COVID-19 create urgent challengers for health providers: Updates on COVID-19 vaccine and Paxlovid.

In this original research we present new emerging data in COVID-19 that create urgent challenges for health providers in prevention and treatment. Health providers should be aware that COVID-19 cases, hospitalizations, and deaths have increased markedly in August 2023. Further, recent data demonstrate a new emerging strain resistant to prior natural and vaccine immunity. The most recent emerging data show that only this updated COVID-19 vaccine produces the same immune response as previous vaccines that reduced mortality by over 95 % and morbidity by over 99 %. This recommendation encompasses all adults and children aged 6 months and older, regardless of whether they have had a prior COVID-19 infection or even if they have never received a prior vaccination. This updated COVID-19 vaccine, approved in September 2023, will be the best means to prevent COVID-19 during this upcoming season of respiratory viruses. In the meanwhile, all members of the US population regardless of previous natural infection, vaccines, or boosters are equally susceptible. At present, health providers should counsel all their patients about masking, social distancing, and avoiding crowds, especially indoors where regions of extreme weather conditions are keeping people indoors in closed quarters. In the treatment of COVID-19 the major clinical challenge to health providers, especially in their Black patients, is to prescribe Paxlovid during the first 5 days after onset of symptoms and a positive test.

Left ventricular fibrosis and CMR tissue characterization of papillary muscles in mitral valve prolapse patients.

PURPOSE: Mitral valve prolapse (MVP) is associated with left ventricle (LV) fibrosis, including the papillary muscles (PM), which is in turn linked to malignant arrhythmias. This study aims to evaluate comprehensive tissue characterization of the PM by cardiovascular magnetic resonance (CMR) imaging and its association with LV fibrosis observed by intraoperative biopsies. METHODS: MVP patients with indication for surgery due to severe mitral regurgitation (n = 19) underwent a preoperative CMR with characterization of the PM: dark-appearance on cine, T1 mapping, conventional bright blood (BB) and dark blood (DB) late gadolinium enhancement (LGE). CMR T1 mapping was performed on 21 healthy volunteers as controls. LV inferobasal myocardial biopsies were obtained in MVP patients and compared to CMR findings. RESULTS: MVP patients (54 ± 10 years old, 14 male) had a dark-appearance of the PM with higher native T1 and extracellular volume (ECV) values compared with healthy volunteers (1096 ± 78ms vs. 994 ± 54ms and 33.9 ± 5.6% vs. 25.9 ± 3.1%, respectively, p < 0.001). Seventeen MVP patients (89.5%) had fibrosis by biopsy. BB-LGE + in LV and PM was identified in 5 (26.3%) patients, while DB-LGE + was observed in LV in 9 (47.4%) and in PM in 15 (78.9%) patients. DB-LGE + in PM was the only technique that showed no difference with detection of LV fibrosis by biopsy. Posteromedial PM was more frequently affected than the anterolateral (73.7% vs. 36.8%, p = 0.039) and correlated with biopsy-proven LV fibrosis (Rho 0.529, p = 0.029). CONCLUSIONS: CMR imaging in MVP patients referred for surgery shows a dark-appearance of the PM with higher T1 and ECV values compared with healthy volunteers. The presence of a positive DB-LGE at the posteromedial PM by CMR may serve as a better predictor of biopsy-proven LV inferobasal fibrosis than conventional CMR techniques.

Neochordal Goldilocks: Analyzing the biomechanics of neochord length on papillary muscle forces suggests higher tolerance to shorter neochordae.

OBJECTIVE: Estimating neochord lengths during mitral valve repair is challenging, because approximation must be performed largely based on intuition and surgical experience. Little data exist on quantifying the effects of neochord length misestimation. We aimed to evaluate the impact of neochord length on papillary muscle forces and mitral valve hemodynamics, which is especially pertinent because increased forces have been linked to aberrant mitral valve biomechanics. METHODS: Porcine mitral valves (n = 8) were mounted in an ex vivo heart simulator, and papillary muscles were fixed to high-resolution strain gauges while hemodynamic data were recorded. We used an adjustable system to modulate neochord lengths. Optimal length was qualitatively verified by a single experienced operator, and neochordae were randomly lengthened or shortened in 1-mm increments up to ±5 mm from the optimal length. RESULTS: Optimal length neochordae resulted in the lowest peak composite papillary muscle forces (6.94 ± 0.29 N), significantly different from all lengths greater than ±1 mm. Both longer and shorter neochordae increased forces linearly according to difference from optimal length. Both peak papillary muscle forces and mitral regurgitation scaled more aggressively for longer versus shorter neochordae by factors of 1.6 and 6.9, respectively. CONCLUSIONS: Leveraging precision ex vivo heart simulation, we found that millimeter-level neochord length differences can result in significant differences in papillary muscle forces and mitral regurgitation, thereby altering valvular biomechanics. Differences in lengthened versus shortened neochordae scaling of forces and mitral regurgitation may indicate different levels of biomechanical tolerance toward longer and shorter neochordae. Our findings highlight the need for more thorough biomechanical understanding of neochordal mitral valve repair.

Combined Value of Dimensionless Index and Transvalvular Flow Rate in Risk Stratification of Aortic Stenosis.

Aortic stenosis (AS) is difficult to phenotype. The metrics of severity are frequently discordant, making prognostication challenging. Flow state is central to accurately determining severity. We sought to evaluate the prognostic value of dimensionless index (DI) and transvalvular flow rate (Q) in AS. We evaluated 2 independent, longitudinal registries of ≥ moderate severity AS (aortic valve area ≤1.5 cm2 or mean gradient ≥20 mm Hg) with complete data follow-up. In the primary cohort (n = 1,104, 77 ± 11 years, 40% female), the DI and Q category significantly predicted mortality (p <0.001) (Figure 1), with the highest risk being low DI and low Q (DI <0.25, Q ≤210 mL/s). In the validation cohort (n = 939, 70 ± 13 years, 42% female), similar results were seen in Kaplan-Meier (p <0.001) and multivariable Cox model analyses (p <0.01). We advocate for wider combined use of DI and Q in AS assessment to augment current diagnostic and prognostic approaches.

Trends in Cigarette Smoking Among United States Adolescents.

Background: Cigarette smoking remains the leading avoidable cause of premature death in the United States, accounting for approximately 500,000, or 1 in 5, deaths annually. We explored trends in cigarette smoking among US adolescents. Methods: We used data for adolescents in grades 9 through 12 from 1991 to 2021 from the Youth Risk Behavior Survey provided by the US Centers for Disease Control and Prevention. We explored trends overall as well as by sex, race/ethnicity, and school grade. Results: All cigarette use-assessed as ever, occasional, frequent, or daily-among adolescents declined markedly from 1991 to 2021. Specifically, ever use significantly decreased from 70.1% in 1991 to 17.8% in 2021 (P<0.05), an almost 4-fold decline. Occasional use significantly decreased from 27.5% in 1991 to 3.8% in 2021 (P<0.05), a greater than 7-fold decline. Frequent use significantly decreased from 12.7% to 0.7%, a greater than 18-fold decline. Daily use declined from 9.8% in 1991 to 0.6% in 2021, a greater than 16-fold decline. Cigarette smoking significantly decreased from 1999 to 2021 across sex, race/ethnicity, and school grade (P<0.05). In 2021, daily use was higher in boys vs girls; Hispanic/Latino and White youth vs Black and Asian youth; and 12th graders vs 9th, 10th, and 11th graders. Conclusion: These data show large and significant decreases in cigarette use among US adolescents in high school grades 9 through 12 from 1991 to 2021. Nonetheless, the data also suggest residual clinical and public health challenges that will require targeted interventions.

Clinical outcomes and progression rate of tricuspid regurgitation in patients with rheumatic mitral valve disease.

OBJECTIVE: A substantial proportion of patients with rheumatic heart disease (RHD) have tricuspid regurgitation (TR). This study aimed to identify the impact of functional TR on clinical outcomes and predictors of progression in a large population of patients with RHD. METHODS: A total of 645 patients with RHD were enrolled, mean age of 47±12 years, 85% female. Functional TR was graded as absent, mild, moderate or severe. TR progression was defined either as worsening of TR degree from baseline to the last follow-up echocardiogram or severe TR at baseline that required surgery or died. Incidence of TR progression was estimated accounting for competing risks. RESULTS: Functional TR was absent in 3.4%, mild in 83.7%, moderate in 8.5% and severe in 4.3%. Moderate and severe functional TR was associated with adverse outcome (HR 1.91 (95% CI 1.15 to 3.2) for moderate, and 2.30 (95% CI 1.28 to 4.13) for severe TR, after adjustment for other prognostic variables. Event-free survival rate at 3-year follow-up was 91%, 72% and 62% in patients with no or mild, moderate and severe TR, respectively. During mean follow-up of 4.1 years, TR progression occurred in 83 patients (13%) with an overall incidence of 3.7 events (95% CI 2.9 to 4.5) per 100 patient-years. In the Cox model, age (HR 1.71, 95% CI 1.34 to 2.17), New York Heart Association functional class III/IV (HR 2.57, 95% CI 1.54 to 4.30), right atrial area (HR 1.52, 95% CI 1.10 to 2.10) and right ventricular (RV) dysfunction (HR 2.02, 95% CI 1.07 to 3.84) were predictors of TR progression. By considering competing risk, the effect of RV dysfunction on TR progression risk was attenuated. CONCLUSIONS: In patients with RHD, functional TR was frequent and associated with adverse outcomes. TR may progress over time, mainly related to right-sided cardiac chambers remodelling.

Evolving Trends in US Mortality from Opioid Overdose: Heroin and Beyond.

OBJECTIVE: Our objective was to explore evolving trends in US drug overdose mortality, overall and by age, sex, race, urbanization, and geography from 1999-2020. METHODS: This is a descriptive epidemiologic study. We used the US Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research and Multiple Cause of Death files from the National Center for Health Statistics. We used crude and age-adjusted cause of death and mortality rate ratios as measures of effects and 95% confidence limits to test for significance. RESULTS: From 1999-2020, drug overdoses caused 1,013,852 deaths and 4.3-fold increase in mortality rate ratios. Subgroup findings were sex (4.5 men, 4.0 women), race (4.6 White, 3.9 Black or African American, 4.0 Asian or Pacific Islanders, 5.1 Native Americans or Alaskan Natives), age (highest 5.6 in 25-34 years, lowest 1.1 in 75-84, and 0.77 in 85+), geography (highest 6.0 in Midwest, lowest 2.6 in West), and urbanization (highest 6.2 in non-metro, lowest 3.7 in metro). CONCLUSIONS: Drug overdoses in the United States from 1999-2020 increased 4.3-fold, with the highest increase in White and Native American or Alaskan Native populations, and Midwest and non-metro areas. The data create preventive and therapeutic challenges, including restrictions on pharmaceutical industries and enhanced efforts by health care providers in safer prescribing. Addiction care should be integrated into all clinical practices, regardless of specialty, and into undergraduate, graduate, and continuing medical education. Targeted interventions are needed to adequately assess patients and provide care. Analytic studies designed a priori are necessary to test hypotheses formulated from these data.