Overview of Spanlastics: A Groundbreaking Elastic Medication Delivery Device with Versatile Prospects for Administration via Various Routes.

When compared to the challenges associated with traditional dosage forms, medication delivery systems based on nanotechnology have been a huge boon. One such candidate for medication delivery is spanlastics, an elastic nanovesicle that can transport a diverse array of medicinal compounds. The use of spanlastics has been associated with an increase in interest in alternative administration methods. The non-ionic surfactant or surfactant blend is the main component of spanlastics. The purpose of this review was primarily to examine the potential of spanlastics as a delivery system for a variety of medication classes administered via diverse routes. Science Direct, Google Scholar, and Pubmed were utilized to search the academic literature for this review. Several studies have demonstrated that spanlastics greatly improve therapeutic effectiveness, increase medication absorption, and decrease drug toxicity. This paper provides a summary of the composition and structure of spanlastics along with their utility in the delivery of various therapeutic agents by adopting different routes. Additionally, it provides an overview of the numerous disorders that may be treated using drugs that are contained in spanlastic vesicles.

Mechanical Circulatory Support Devices in Patients with High-Risk Pulmonary Embolism.

Pulmonary embolism (PE) is a common acute cardiovascular condition. Within this review, we discuss the incidence, pathophysiology, and treatment options for patients with high-risk and massive pulmonary embolisms. In particular, we focus on the role of mechanical circulatory support devices and their possible therapeutic benefits in patients who are unresponsive to standard therapeutic options. Moreover, attention is given to device selection criteria, weaning protocols, and complication mitigation strategies. Finally, we underscore the necessity for more comprehensive studies to corroborate the benefits and safety of MCS devices in PE management.

Collating the voice of people with autoimmune diseases: Methodology for the Third Phase of the COVAD Studies.

INTRODUCTION: The growing recognition of holistic patient care highlights the various factors shaping the quality of life of individuals with autoimmune and rheumatic diseases (AIRDs). Beyond the traditional disease measures, there is an emerging acknowledgment of the less-explored aspects, including subjective well-being, social determinants of health, comorbidities, mental health, and medication adherence. Moreover, digital health services have empowered patients to engage actively in decision-making alongside clinicians. To explore these domains within the context of AIRDs, the "Collating the Voice of People with Autoimmune Diseases" COVAD survey was conceived, a successor of the previous two COVAD surveys. In this document, we present the study protocol in comprehensive detail. METHODS: The COVAD-3 survey is a cross-sectional patient self-reported e-survey incorporating multiple widely accepted scales/scores to assess various aspects of patients' lifestyles objectively. To ensure the survey's accuracy and usability across diverse regions, it will be translated into multiple languages and subjected to rigorous vetting and pilot testing. It will be distributed by collaborators via online platforms and data will be collected from patients with AIRDs, and healthy individuals over eight months. Data analysis will focus on outcome measures related to various social, demographic, economic, and psychological factors. CONCLUSION: With the increasing awareness to adopt a holistic treatment approach encompassing all avenues of life, the COVAD-3 survey aims to gain valuable insights into the impact of social, demographic, economic, and psychological determinants of health on the subjective well-being in patients with AIRDs, which will contribute to a better understanding of their overall health and well-being.

Maternal and Fetal Outcomes in Pulmonary Hypertension During Pregnancy: A Contemporary Nationwide Analysis.

Pulmonary hypertension (PH) disproportionately affects women, presenting challenges during pregnancy. Historically, patients with PH are advised to avoid pregnancy; however, recent reports have indicated that the incidence of adverse events in pregnant patients with PH may be lower than previously reported. We conducted a retrospective cohort study in pregnant patients with PH using the National Readmission Database from January 1, 2016, to December 31, 2020. PH was categorized according to the World Health Organization classification. Primary end points include maternal mortality and 30-day nonelective readmission rate. Other adverse short-term maternal (cardiovascular and obstetric) and fetal outcomes were also analyzed. Of 9,922,142 pregnant women, 3,532 (0.04%) had PH, with Group 1 PH noted in 1,833 (51.9%), Group 2 PH in 676 (19.1%), Group 3 PH in 604 (17.1%), Group 4 PH in 23 (0.7%), Group 5 PH in 98 (2.8%), and multifactorial PH in 298 (8.4%). PH patients exhibited higher rates of adverse cardiovascular events (15.7% vs 0.3% without PH, p <0.001) and mortality (0.9% vs 0.01% without PH, p <0.001). Mixed PH and Group 2 PH had the highest prevalence of adverse cardiovascular events in the World Health Organization PH groups. Patients with PH had a significantly higher nonelective 30-day readmission rate (10.4% vs 2.3%) and maternal adverse obstetric events (24.2% vs 9.1%) compared with those without PH (p <0.001) (Figure 1). In conclusion, pregnant women with PH had significantly higher adverse event rates, including in-hospital maternal mortality (85-fold), compared with those without PH.

Status and Future Directions for Balloon Pulmonary Angioplasty in Chronic Thromboembolic Pulmonary Disease With and Without Pulmonary Hypertension: A Scientific Statement From the American Heart Association.

Balloon pulmonary angioplasty continues to gain traction as a treatment option for patients with chronic thromboembolic pulmonary disease with and without pulmonary hypertension. Recent European Society of Cardiology guidelines on pulmonary hypertension now give balloon pulmonary angioplasty a Class 1 recommendation for inoperable and residual chronic thromboembolic pulmonary hypertension. Not surprisingly, chronic thromboembolic pulmonary hypertension centers are rapidly initiating balloon pulmonary angioplasty programs. However, we need a comprehensive, expert consensus document outlining critical concepts, including identifying necessary personnel and expertise, criteria for patient selection, and a standardized approach to preprocedural planning and establishing criteria for evaluating procedural efficacy and safety. Given this lack of standards, the balloon pulmonary angioplasty skill set is learned through peer-to-peer contact and training. This document is a state-of-the-art, comprehensive statement from key thought leaders to address this gap in the current clinical practice of balloon pulmonary angioplasty. We summarize the current status of the procedure and provide a consensus opinion on the role of balloon pulmonary angioplasty in the overall care of patients with chronic thromboembolic pulmonary disease with and without pulmonary hypertension. We also identify knowledge gaps, provide guidance for new centers interested in initiating balloon pulmonary angioplasty programs, and highlight future directions and research needs for this emerging therapy.

In-Hospital Outcomes of Combined Coronary Revascularization and Transcatheter Aortic Valve Implantation in Inpatient Nationwide Analysis.

Transcatheter aortic valve implantation (TAVI) is accepted as an alternative to surgery, but data on combined percutaneous coronary interventions (PCI) and TAVI during the same in-hospital stay are still lacking. Using the national inpatient sample (NIS) database, we identified all TAVI encounters and compared in-hospital outcomes of patients who had TAVI only to patients who had TAVI and PCI. We used multivariable logistic regression analysis to calculate the adjusted odds ratio (aOR). Of 291,810 patient encounters with TAVI, 13,114 (4.5%) had combined PCI during the same index admission. The average age was 79.61 ± 8.61 years in the TAVI-only vs 80.25 ± 8.73 years in the combined TAVI-PCI group. Combined TAVI and PCI was associated with higher in-hospital mortality (4.5% vs 1.8%, aOR: 2.3), stroke (4.7% vs 2.9%, aOR: 1.4), net adverse events (NAE) (20.2% vs 5.7%, aOR: 3.6), major bleeding (40.1% vs 24.3%, aOR: 1.8), vascular complications (10.6% vs 2.5%, aOR: 3.9), acute kidney injury (AKI) (23.3% vs 11.7%, aOR: 2.1), hemodialysis (HD) (4.2% vs 2.4%, aOR: 1.4), postoperative cardiogenic shock (1.2% vs 0.4%, aOR: 2.8), need for mechanical circulatory support (6.9% vs 1%, aOR: 7); p-value < 0.001 for all. The utilization of permanent pacemakers was similar between the groups (9.8% vs 9.2%, aOR: 1; p = 0.6). Combining TAVI and PCI during the same index admission is associated with worse outcomes. The decision to do PCI for patients undergoing TAVI should be individualized and tailored based on the patient's clinical conditions.

Comparative Outcomes of Catheter-Directed Thrombolysis Plus Systemic Anticoagulation Versus Systemic Anticoagulation Alone in the Management of Intermediate-Risk Pulmonary Embolism in a Systematic Review and Meta-Analysis.

There are limited and conflicting data on the initial management of intermediate-risk (or submassive) pulmonary embolism (PE). This study sought to compare the outcomes of catheter-directed thrombolysis (CDT) in combination with systemic anticoagulation (SA) to SA alone. A systematic search was conducted in MEDLINE, EMBASE, PubMed, and the Cochrane databases from inception to March 1, 2023 for studies comparing the outcomes of CDT + SA versus SA alone in intermediate-risk PE. The outcomes were in-hospital, 30-day, 90-day, and 1-year mortality; bleeding; blood transfusion; right ventricular recovery; and length of stay. Random-effects models was used to calculate the pooled incidence and risk ratios (RRs) with 95% confidence intervals (CIs). A total of 15 (2 randomized and 13 observational) studies with 10,549 (2,310 CDT + SA and 8,239 SA alone) patients were included. Compared with SA, CDT + SA was associated with significantly lower in-hospital mortality (RR 0.41, 95% CI 0.30 to 0.56, p <0.001), 30-day mortality (RR 0.34, 95% CI 0.18 to 0.67, p = 0.002), 90-day mortality (RR 0.34, 95% CI 0.17 to 0.67, p = 0.002), and 1-year mortality (RR 0.58, 95% CI 0.34 to 0.97, p = 0.04). There were no significant differences between the 2 cohorts in the rates of major bleeding (RR 1.39, 95% CI 0.72 to 2.68, p = 0.56), minor bleeding (RR 1.83, 95% CI 0.97 to 3.46, p = 0.06), and blood transfusion (RR 0.34, 95% CI 0.10 to 1.15, p = 0.08). In conclusion, CDT + SA is associated with significantly lower short-term and long-term all-cause mortality, without any differences in major/minor bleeding, in patients with intermediate-risk PE.

Expert Recommendations on Optimizing the Diagnosis and Management of Gastroesophageal Reflux Disease Associated with Comorbidities in the Indian Population.

Gastroesophageal reflux disease (GERD) is among the most prevalent gastrointestinal (GI) disorders. It is known to often coexist with other chronic diseases such as asthma, chronic obstructive pulmonary disease (COPD), obesity, diabetes mellitus (DM), and hypertension. Upper endoscopy, esophageal manometry, and impedance-pH monitoring are a few invasive diagnostic options that are reserved for selected GERD patients. Symptom assessment by using questionnaires, such as the frequency scale for the symptoms of GERD (FSSG), is simple, convenient, noninvasive, and inexpensive. These questionnaires are widely used to facilitate diagnosis and appropriate treatment. Early diagnosis of GERD and timely management may improve clinical outcomes in patients. Proton pump inhibitors (PPIs) are the preferred therapy for GERD. However, evidence indicates that excessive and extended use of PPIs is linked to adverse events. An overview of the diagnosis and management of GERD, as well as an evidence-based overview of the relationship between GERD and asthma, COPD, obesity, DM, and hypertension, is presented in this review. Expert opinions and recommendations for diagnosing GERD using invasive tests and validated questionnaires have also been mentioned.

Sex, Racial, and Geographic Disparities in Pulmonary Embolism-related Mortality Nationwide.

Rationale: Acute pulmonary embolism is a leading cause of cardiovascular death. There are limited data on the national mortality trends from pulmonary embolism. Understanding these trends is crucial for addressing the mortality and associated disparities associated with pulmonary embolism. Objectives: To analyze the national mortality trends related to acute pulmonary embolism and determine the overall age-adjusted mortality rate (AAMR) per 100,000 population for the study period and assess changes in AAMR among different sexes, races, and geographic locations. Methods: We conducted a retrospective cohort analysis using mortality data of individuals aged ⩾15 years with pulmonary embolism listed as the underlying cause of death in the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database from January 2006 to December 2019. These data are produced by the National Center for Health Statistics. Results: A total of 109,992 pulmonary embolism-related deaths were noted in this dataset nationwide between 2006 and 2019. Of these, women constituted 60,113 (54.7%). The AAMR per 100,000 was not significantly changed, from 2.84 in 2006 to 2.81 in 2019 (average annual percentage change [AAPC], 0.2; 95% confidence interval [CI], -0.1 to 0.5; P = 0.15). AAMR increased for men throughout the study period compared with women (AAPC, 0.7 for men; 95% CI, 0.3 to 1.2; P = 0.004 vs. AAPC, -0.4 for women; 95% CI, -1.1 to 0.3; P = 0.23, respectively). Similarly, AAMR for pulmonary embolism increased for Black compared with White individuals, from 5.18 to 5.26 (AAPC, 0.4; 95% CI, 0.0 to 0.7; P = 0.05) and 2.82 to 2.86 (AAPC, 0.0; 95% CI, -0.6 to 0.6; P = 0.99), respectively. Similarly, AAMR for pulmonary embolism was higher in rural areas than in micropolitan and large metropolitan areas during the study period (4.07 [95% CI, 4.02 to 4.12] vs. 3.24 [95% CI, 3.21 to 3.27] vs. 2.32 [95% CI, 2.30-2.34], respectively). Conclusions: Pulmonary embolism mortality remains high and unchanged over the past decade, and enduring sex, racial and socioeconomic disparities persist in pulmonary embolism. Targeted efforts to decrease pulmonary embolism mortality and address such disparities are needed.

The Intersection of Pulmonary Vascular Disease and Hypoxia-Inducible Factors.

Hypoxia-inducible factors (HIFs) are a family of nuclear transcription factors that serve as the master regulator of the adaptive response to hypoxia. In the lung, HIFs orchestrate multiple inflammatory pathways and signaling. They have been reported to have a major role in the initiation and progression of acute lung injury, chronic obstructive pulmonary disease, pulmonary fibrosis, and pulmonary hypertension. Although there seems to be a clear mechanistic role for both HIF 1α and 2α in pulmonary vascular diseases including PH, a successful translation into a definitive therapeutic modality has not been accomplished to date.

Effects of Valvular Heart Disease on Clinical Outcomes in Sarcoidosis.

Systemic sarcoidosis can lead to heart failure, conduction abnormalities and ventricular arrhythmias although data on concomitant valvular heart disease (VHD) is limited. We reported the prevalence and outcomes of VHD in systemic sarcoidosis. A retrospective cohort study was conducted using National Inpatient Sample between 2016 and 2020 with respective ICD-10-CM codes. 406,315 patients were hospitalized with sarcoidosis, out of which 20,570 had comorbid VHD (5.1%). Mitral disease was most common (2.5%), followed by aortic, and tricuspid disease. Tricuspid disease was associated with increased mortality in sarcoidosis (OR 1.6, 95% CI, 1.1-2.6, P = 0.04), while aortic disease was associated with higher mortality in only 31-50 years age cohort. Patients with sarcoidosis and VHD have higher hospitalization charges and lower or similar valvular intervention rates than those without sarcoidosis. VHD has a prevalence of 5% in sarcoidosis, predominantly affecting mitral and aortic valves. Underlying VHD is associated with worse outcomes in sarcoidosis.

Periprocedural Complications With Balloon Pulmonary Angioplasty: Analysis of Global Studies.

BACKGROUND: Balloon pulmonary angioplasty (BPA) was introduced as a treatment modality for patients with inoperable, medically refractory chronic thromboembolic pulmonary hypertension decades ago; however, reports of high rates of pulmonary vascular injury have led to considerable refinement in procedural technique. OBJECTIVES: The authors sought to better understand the evolution of BPA procedure-related complications over time. METHODS: The authors conducted a systematic review of original articles published by pulmonary hypertension centers globally and performed a pooled cohort analysis of procedure-related outcomes with BPA. RESULTS: This systematic review identified 26 published articles from 18 countries worldwide from 2013 to 2022. A total of 1,714 patients underwent 7,561 total BPA procedures with an average follow up of 7.3 months. From the first period (2013-2017) to the second period (2018-2022), the cumulative incidence of hemoptysis/vascular injury decreased from 14.1% (474/3,351) to 7.7% (233/3,029) (P < 0.01); lung injury/reperfusion edema decreased from 11.3% (377/3,351) to 1.4% (57/3,943) (P < 0.01); invasive mechanical ventilation decreased from 0.7% (23/3,195) to 0.1% (4/3,062) (P < 0.01); and mortality decreased from 2.0% (13/636) to 0.8% (8/1,071) (P < 0.01). CONCLUSIONS: Procedure-related complications with BPA, including hemoptysis/vascular injury, lung injury/reperfusion edema, mechanical ventilation, and death, were less common in the second period (2018-2022), compared with first period (2013-2017), likely from refinement in patient and lesion selection and procedural technique over time.

Varied Presentation of Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C): A Case Series.

Arrhythmogenic right ventricular dysplasia (ARVD) is a genetically predisposed form of cardiomyopathy that mainly affects young individuals resulting in fatal ventricular arrhythmias leading to sudden cardiac death. ARVD has 50% of cases that involve both the right ventricle (RV) and left ventricle (LV), but only a small number of cases involve an isolated left ventricle. In this case series, five patients (four males and one female) with a diagnosis of ARVD presented to our center with varied clinical presentations across a wide range of age groups. The MRI of all five cases showed dilated right atrium (RA)/RV with right ventricular free wall dyskinesia. Two-dimensional (2D) MRI showed aneurysmal outpouching with diffuse free wall enhancement. Automated implantable cardioverter defibrillator (AICD) was implanted uneventfully in all five patients, and the patients were discharged with oral medications such as low-dose diuretics, beta-blockers, spironolactone, angiotensin-converting enzymes (ACE) inhibitors, amiodarone, and anxiolytics. Until now, the patients were doing well on follow-up visits. The therapeutic management of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) has evolved over the years and continues to be an important challenge. To further improve risk stratification and treatment of patients, more information is needed on natural history, long-term prognosis, and risk assessment. Special attention should be focused on the identification of patients who would benefit from implantable cardioverter-defibrillator (ICD) implantation in comparison to pharmacological and other nonpharmacological approaches.

Study of left ventricular systolic dysfunction, left ventricular diastolic dysfunction and pulmonary hypertension in CKD 3b-5ND patients-A single centre cross-sectional study.

INTRODUCTION: Cardiovascular diseases are associated with increased morbidity and mortality among CKD (chronic kidney disease) population. Recent studies have found increasing prevalence of PH (pulmonary hypertension) in CKD population. Present study was done to determine prevalence and predictors of LV (left ventricular) systolic dysfunction, LVDD (left ventricular diastolic dysfunction) and PH in CKD 3b-5ND (non-dialysis) patients. METHODS: A cross sectional observational study was done from Jan/2020 to April/2021. CKD 3b-5ND patients aged ≥15 yrs were included. Transthoracic 2D (2 dimensional) echocardiography was done in all patients. PH was defined as if PASP (pulmonary artery systolic pressure) value above 35mm Hg, LV systolic dysfunction was defined as LVEF (left ventricular ejection fraction)≤50% and LVDD as E/e' ratio >14 respectively. Multivariate logistic regression model was done to determine the predictors. RESULTS: A total of 378 patients were included in the study with 103 in stage 3b, 175 in stage 4 and 100 patients in stage 5ND. Prevalence of PH was 12.2%, LV systolic dysfunction was 15.6% and LVDD was 43.65%. Predictors of PH were duration of CKD, haemoglobin, serum 25-OH vitamin D, serum iPTH (intact parathyroid hormone) and serum albumin. Predictors of LVDD were duration of CKD and presence of arterial hypertension. Predictors of LV systolic dysfunction were eGFR (estimated glomerular filtration rate), duration of CKD, serum albumin and urine protein. CONCLUSION: In our study of 378 CKD 3b-5ND patients prevalence of PH was 12.2%, LV systolic dysfunction was 15.6% and LVDD was 43.65%.

Pathogenesis, Diagnosis, and Management of Chronic Thromboembolic Pulmonary Hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is thought to occur as a sequelae of thromboembolic processes in the pulmonary vasculature. The pathophysiology of CTEPH is multifactorial, including impaired fibrinolysis, endothelial dysregulation, and hypoxic adaptations. The diagnosis of CTEPH is typically delayed considering the nonspecific nature of the symptoms, lack of screening, and relatively low incidence. Diagnostic tools include ventilation-perfusion testing, echocardiography, cardiac catheterization, and pulmonary angiography. The only potentially curative treatment for CTEPH is pulmonary endarterectomy However, approximately 40% of patients are inoperable. Currently, only Riociguat is Food and Drug Administration approved specifically for CTEPH, with additional drug trials underway.

Known Unknowns in the Contemporary Management of High-Risk Pulmonary Embolism: What Do the Guidelines Tell Us.

Pulmonary embolism (PE) is a life-threatening condition with increasing hospital admissions. Prompt identification and treatment of PE patients with hemodynamic collapse are essential. Conflicting recommendations and weak evidence hinder effective management of PE, resulting in unchanged mortality rates despite advancements in therapies. Current risk stratification lacks granularity, necessitating a more detailed classification to guide treatment, predict outcomes, and improve patient selection for clinical trials. This article reviews clinical practice guidelines from major North American and European societies, emphasizing the need for more research and guidance to improve mortality and morbidity outcomes in PE.

Novel Risk Stratification and Hemodynamic Profiling in Acute Pulmonary Embolism: A Proposed Classification Inspired by Society for Cardiovascular Angiography and Intervention Shock Staging.

Treatment options for patients with acute pulmonary embolism (PE) and right ventricular shock (RVS) have grown exponentially. Therapy options include anticoagulation, systemic thrombolysis, catheter-based thrombolysis/ thrombectomy, and may include short-term mechanical circulatory support. However, the incidence of short-term morbidity and mortality has not changed despite the emergence of several advanced therapies in acute PE. This is possibly due to the inclusion of heterogenous populations in research studies without differentiation based on the acuity/severity of presentation. We propose a novel classification for PE-RVS to allow for standardizing appropriate therapy escalation and better communication of the severity among cardiovascular critical care, and emergency health care professionals.