An Overview of the Pharmacokinetics and Pharmacodynamics of Landiolol (an Ultra-Short Acting ß1 Selective Antagonist) in Atrial Fibrillation.

Landiolol is an ultra-short-acting, selective ß1-adrenergic receptor blocker that was originally approved in Japan for the treatment of intraoperative tachyarrhythmias. It has gained attention for its use in the management of tachyarrhythmias and perioperative tachycardia, especially atrial fibrillation for both cardiac and non-cardiac surgeries. It can be the ideal agent for heart rate control due to its high ß1-selectivity, potent negative chronotropic effect, a limited negative inotropic potential, and an ultrashort elimination half-life (around 4 min); moreover, it may have a potential therapeutic effects for sepsis and pediatric patients. Landiolol seems to be superior to other short-acting and selective beta-blockers such as esmolol. This review aims to provide a comprehensive overview of landiolol, a new ultra-short-acting ß1 selective antagonist, including its pharmacology, clinical applications, efficacy, safety profile, and future directions in research and clinical data.

Targeting Common Inflammatory Mediators in Experimental Severe Asthma and Acute Lung Injury.

Neutrophils, known to be mobilized and activated in high amounts through Il-17 stimulation, are a key factor for clinical manifestation and imbalance of redox systems favoring a dominant oxidative state in both severe asthma and acute lung injury (f). The aim of this study was to evaluate in mice, the effect of Secukinumab (SECU) in a model of ovalbumin-induced asthma exacerbated with LPS administration to induce ALI, compared to dexamethasone (DEXA), already known for its benefit in both asthma and ALI. Results on cytokine levels for specific Th1, Th2 and Th17 revealed an interplay of immune responses. For Th1 effector cytokines in BALF, DEXA treatment increased TNF-α levels, but TNF-α was not modified by SECU; DEXA and SECU significantly decreased IFN-γ and IL-6 levels. For typical Th2 cytokines, DEXA significantly increased Il-4, Il-5 and Il-13 levels, while SECU significantly inhibited Il-5 levels. Both SECU and DEXA significantly decreased Il-17 levels. Cytokine level changes in lung tissue homogenate were partly similar to BALF cytokines. Conclusion: in addition to DEXA, SECU possesses the ability to modulate inflammatory cytokine release and to decrease Th17 responses in ALI overlapped on exacerbated asthma in mice.

Multimodality Imaging in Right Heart Tumors: Proposed Algorithm towards an Appropriate Diagnosis.

A right heart tumor can be identified by transthoracic echocardiography during a routine examination or due to cardiac symptoms. The first step is the assessment by echocardiography, with its multiple techniques, and the obtained information must be judged in a clinical and biological context. The second step comprises one, sometimes even two, of the more complex modality imaging methods. The choice is driven not only by the advantages of each imaging technique but also by local expertise or the preferred imaging modality in the center. This step is followed by staging, follow-up, and/or imaging-guided excision or biopsy, which is performed in selected cases in order to obtain anatomopathological confirmation. In the presence of features suggestive of malignancy or causing hemodynamic impairment, a transvenous biopsy is essential before the more complex imaging modalities (which are still relevant in the staging process). Using a structured imaging approach, it is possible to reach an appropriate diagnosis without a biopsy. Frequently, these imaging techniques have a complementary role, so an integrated imaging approach is recommended. This proposed algorithm for appropriate diagnosis of right heart tumors could serve as a practical guide for clinicians (not only imaging specialists).

Exploring the Intersection of Artificial Intelligence and Clinical Healthcare: A Multidisciplinary Review.

Artificial intelligence (AI) plays a more and more important role in our everyday life due to the advantages that it brings when used, such as 24/7 availability, a very low percentage of errors, ability to provide real time insights, or performing a fast analysis. AI is increasingly being used in clinical medical and dental healthcare analyses, with valuable applications, which include disease diagnosis, risk assessment, treatment planning, and drug discovery. This paper presents a narrative literature review of AI use in healthcare from a multi-disciplinary perspective, specifically in the cardiology, allergology, endocrinology, and dental fields. The paper highlights data from recent research and development efforts in AI for healthcare, as well as challenges and limitations associated with AI implementation, such as data privacy and security considerations, along with ethical and legal concerns. The regulation of responsible design, development, and use of AI in healthcare is still in early stages due to the rapid evolution of the field. However, it is our duty to carefully consider the ethical implications of implementing AI and to respond appropriately. With the potential to reshape healthcare delivery and enhance patient outcomes, AI systems continue to reveal their capabilities.

Pathogenic Connections in Post-COVID Conditions: What Do We Know in the Large Unknown? A Narrative Review.

The coronavirus 2019 (COVID-19) disease has long-term effects, known as post-COVID conditions (PCC) or long-COVID. Post-COVID-19 syndrome is defined by signs and symptoms that occur during or after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection which persist for more than 12 weeks and cannot be supported by an alternative diagnosis. The cardiovascular damage caused by COVID-19 in the severe forms of the disease is induced by severe systemic inflammation, considered to be one of the causes of myocardial lesions, with increased levels of circulating cytokines and toxic response mediators. We have focused on conditions that can induce long-COVID-19, or multisystem inflammatory syndrome in adults or children (MIS-C/MIS-A), with an emphasis on endocrinological and metabolic disorders. Although described less frequently in children than in adults, long-COVID syndrome should not be confused with MIS-C, which is an acute condition characterized by multisystem involvement and paraclinical evidence of inflammation in a pediatric patient who tested positive for SARS-CoV-2. At the same time, we mention that the MIS-A symptoms remit within a few weeks, while the duration of long-COVID is measured in months. Long-COVID syndrome, along with its complications, MIS-A and MIS-C, represents an important challenge in the medical community. Underlying comorbidities can expose both COVID-19 adult and pediatric patients to a higher risk of negative outcomes not only during, but in the aftermath of the SARS-CoV-2 infection as well.

Curcumin as a Natural Approach of Periodontal Adjunctive Treatment and Its Immunological Implications: A Narrative Review.

Scaling and root planing represent the gold standard in the treatment of periodontal disease, but these therapeutic methods cannot eliminate the remaining periodontopathogenic bacteria in cement, tubules, and periodontal soft tissue. Thus, a number of additional therapeutic means have been adopted, including local and systemic antibiotic therapy, as well as the use of photodynamic therapy techniques. Recently, special attention has been paid to potential phytotherapeutic means in the treatment of periodontal disease. In this review, we aim to present the effects generated by the extract of Curcuma longa, the various forms of application of turmeric as an additional therapeutic means, as well as the aspects related to its biotolerance.

Inhaled interferons beta and SARS-COV2 infection: a preliminary therapeutic perspective.

INTRODUCTION: SARS-COV2 infection represents a therapeutic challenge due to the limited number of effective therapies available and due to the fact that it is not clear which host response in terms of inflammation pattern is the most predictive for an optimal (and rapid) recovery. Interferon ß pathway is impaired in SARS-COV2 infection and this is associated with a bigger disease burden. Exogenous inhaled interferon might be beneficial in this setting. AREAS COVERED: Nebulized interferon-ß is currently investigated as a potential therapy for SARS-COV2 because the available data from a phase II study demonstrate that this medication is able to accelerate the recovery from disease. EXPERT OPINION: Further clinical studies are needed in order to better document the efficacy of this therapy especially in severe forms of COVID-19, the optimal duration of therapy and if such a medication is appropriate for domiciliary use. Also combined regimens with antivirals or with compounds which are able to enhance the endogenous production of interferon might be of promise.

The Influence of Socioeconomic Status on the Prognosis and Profile of Patients Admitted for Acute Heart Failure during COVID-19 Pandemic: Overestimated Aspects or a Multifaceted Hydra of Cardiovascular Risk Factors?

Background: Heart failure (HF) is a complex clinical syndrome that represents a great burden on public health systems due to its increased prevalence, disability and mortality rates. There are multiple triggers that can induce or aggravate a preexisting HF, socioeconomic status (SES) emerging as one of the most common modifiable risk factors. Our study aimed to analyze the influence of certain SES indicators on the outcome, clinical aspects and laboratory parameters of patients with HF in North-Eastern Romania, as well as their relationship with other traditional cardiovascular risk factors. Methods: We conducted a prospective, single-center study comprising 120 consecutively enrolled patients admitted for acute HF. The evaluation of individual SES was based upon a standard questionnaire and evidence from official documents. Results: the patients' age ranged between 18 and 94 years; Out of 120 patients, 49 (40.8%) were women and 71 (59.2%) were men, residing in rural 59 (49.2%) or urban 61 (50.8%) areas. 14.2% were university graduates, while 15.8% had only attended primary school. The majority of the patients are or were employed in the service sector (54.5%), followed by industry (29.2%) and agriculture (20%). The mean monthly income was 306.1 ± 177.4 euro, while the mean hospitalization cost was 2471.8 ± 2073.8 euro per patient. The individual income level was positively correlated with urban area of residence, adequate household sanitation facilities and healthcare access, and negatively associated with advanced age and previous hospitalizations due to HF. However, the individual financial situation was also positively correlated with the increased prevalence of certain cardiovascular risk factors, such as arterial hypertension, anemia or obesity, but not with total cholesterol or male gender. Concerning the direct impact of a poor economic status upon prognosis in the setting of acute HF, our results showed no statistically significant differences concerning the in-hospital or at 1-month follow-up mortality rates. Rather than inducing a direct impact on the short-term outcome, these findings concerning SES indicators are meant to enhance the implementation of policies aimed to provide adequate healthcare for people from all social layers, with a primary focus on modifiable cardiovascular risk factors.

Beyond the Finish Line: The Impact and Dynamics of Biomarkers in Physical Exercise-A Narrative Review.

The research of biomarkers continues to emerge as a developing academic field which is attracting substantial interest. The study of biomarkers proves to be useful in developing and implementing new screening methods for a wide variety of diseases including in the sports area, whether for leisure activities or professional sports. Novel research has brought into question the immune system and the limitations it may impose on sports practicing. As the well-being of athletes is a priority, the state of their immune function offers valuable information regarding their health status and their ability to continue training. The assessment of various biomarkers may contribute to a more accurate risk stratification and subsequent prevention of some invalidating or even fatal pathologies such as the sudden cardiac death. Therefore, we have reviewed several studies that included sports-related pathology or specific morphofunctional alterations for which some immune biomarkers may represent an expression of the underlying mechanism. These include the defensins, immunoglobulin A (IgA), interleukin-6 (IL-6), the tumoral necrosis factor α (TNF-α), and the white blood cells (WBC) count. Similarly, also of significant interest are various endocrine biomarkers, such as cortisol and testosterone, as well as anabolic or catabolic markers, respectively. Literature data highlight that these values are greatly influenced not only by the duration, but also by the intensity of the physical exercise; moderate training sessions actually enhance the immune function of the body, while a significant increase in both duration and intensity of sports activity acts as a deleterious factor. Therefore, in this paper we aim to highlight the importance of biomarkers' evaluation in connection with sports activities and a subsequent more adequate approach towards personalized training regimens.

Marine-Derived Compounds for the Potential Treatment of Glucocorticoid Resistance in Severe Asthma.

One of the challenges to the management of severe asthma is the poor therapeutic response to treatment with glucocorticosteroids. Compounds derived from marine sources have received increasing interest in recent years due to their prominent biologically active properties for biomedical applications, as well as their sustainability and safety for drug development. Based on the pathobiological features associated with glucocorticoid resistance in severe asthma, many studies have already described many glucocorticoid resistance mechanisms as potential therapeutic targets. On the other hand, in the last decade, many studies described the potentially anti-inflammatory effects of marine-derived biologically active compounds. Analyzing the underlying anti-inflammatory mechanisms of action for these marine-derived biologically active compounds, we observed some of the targeted pathogenic molecular mechanisms similar to those described in glucocorticoid (GC) resistant asthma. This article gathers the marine-derived compounds targeting pathogenic molecular mechanism involved in GC resistant asthma and provides a basis for the development of effective marine-derived drugs.

Insights into multidrug-resistant K. pneumoniae urinary tract infections: From susceptibility to mortality.

The incidence of urinary tract infections (UTIs) caused by Klebsiella pneumoniae has exhibited an increasing trend and has become a high burden for many public health systems, especially in hospital settings. Multidrug resistance associated with the production of extended-spectrum ß-lactamases (ESBL) among K. pneumoniae isolates is endemic in Southeastern Europe. We retrospectively analyzed 75 cases admitted to 'St. Parascheva' Clinical Hospital of Infectious Diseases in Iasi, Romania, during the first 6 months of 2019 (January 1 to June 30), who had a confirmed diagnosis of K. pneumoniae UTI at discharge. From a total of 75 patients, 34 (45.3%) presented ESBL+ K. pneumoniae. The mean age was 66 years (70.1 for the ESBL+ patients vs. 62.6 for the ESBL- patients, P=0.0365). There was a symmetrical sex distribution (37 men vs. 38 women). Of these, 22 men had ESBL+ K. pneumoniae UTIs, compared to only 15 with an ESBL- strain, P=0.0087. Another risk factor for ESBL+ K. pneumoniae UTIs was the presence of hospitalization in the past 6 months; 20 (58.82%) patients with ESBL+ infections were previously hospitalized, compared to only 5 (12.19%) patients with ESBL- strains, P<0.0001. The urinary catheter carriers presented an increased prevalence of ESBL+ infections (15/34 vs. 5/41, P=0.0012). Regarding mortality, ESBL+ infections caused 6 fatalities, compared to only 1 death in the ESBL- group, P=0.0166. ESBL+ K. pneumoniae strains represent an important cause of healthcare-related UTIs, with a significantly higher mortality rate compared to ESBL- strains. Early identification and adequate management of the risk factors incriminated in ESBL+ UTIs should be a priority for physicians in order to limit the dissemination of the ESBL-producing strains and thus to improve the outcome of these patients.

Latest Insights into Mechanisms behind Atrial Cardiomyopathy: It Is Not always about Ventricular Function.

Atrial cardiomyopathy (ACM) represents a constantly evolving concept, with increasing importance in contemporary research and clinical practice. A better understanding of the mechanisms involved in atrial remodeling and its clinical correlations especially with atrial fibrillation (AF) and other cardiometabolic comorbidities may induce a significant impact on the diagnosis, prognosis, and therapeutic approach of ACM-related comorbidities. Although initially described several decades ago, investigators have only recently highlighted that several renal, metabolic, and cardiovascular diseases are determining factors for atrial remodeling and subsequent ACM. Based on data from multiple recent studies, our research emphasizes the correlations between ACM and other coexisting pathologies including cardiovascular, respiratory, or metabolic diseases, with fibrosis being the most incriminated pathophysiological mechanism. In addition to the usual tests, the paraclinical assessment of ACM is increasingly based on the use of various cardiac biomarkers, while the cardiac magnetic resonance (CMR) has become an increasingly tempting diagnostic too for describing morphofunctional aspects of the heart chambers, with the gadolinium contrast enhanced CMR (LGE-CMR) emerging as a commonly used technique aiming to identify and quantify the precise extent of atrial fibrosis. Further research should be conducted in order to clarify our knowledge regarding atrial remodeling and, therefore, to develop new and improved therapeutic approaches in these patients.

The Professional and Psycho-Emotional Impact of the COVID-19 Pandemic on Medical Care-A Romanian GPs' Perspective.

The aim of this study was to assess the psycho-emotional impact and the adjustment degree of Romanian general practitioners (GPs) in the coronavirus disease 2019 (COVID-19) pandemic context. With a cross-sectional design, the study included 677 GPs to whom a validated questionnaire based on different items targeting three factors was sent: burden of prevention, presence of stress symptoms, and adjustment to pandemic. The burden of prevention and the adjustment effort to the pandemic were felt significantly more by female doctors and by GPs working in associated offices. The case definition quality, the support received, the professional life changes, and the stress symptoms proved to be the main predictors for the adjustment to pandemic. The adjustment measurement questionnaire can be used in further studies to identify the most supportive public health practices in difficult epidemiological contexts.