The Rare Condition of Left Ventricular Non-Compaction and Reverse Remodeling.

Left ventricular non-compaction (LVNC) is a rare disease defined by morphological criteria, consisting of a two-layered ventricular wall, a thin compacted epicardial layer, and a thick hyper-trabeculated myocardium layer with deep recesses. Controversies still exist regarding whether it is a distinct cardiomyopathy (CM) or a morphological trait of different conditions. This review analyzes data from the literature regarding diagnosis, treatment, and prognosis in LVNC and the current knowledge regarding reverse remodeling in this form of CM. Furthermore, for clear exemplification, we report a case of a 41-year-old male who presented symptoms of heart failure (HF). LVNC CM was suspected at the time of transthoracic echocardiography and was subsequently confirmed upon cardiac magnetic resonance imaging. A favorable remodeling and clinical outcome were registered after including an angiotensin receptor neprilysin inhibitor in the HF treatment. LVNC remains a heterogenous CM, and although a favorable outcome is not commonly encountered, some patients respond well to therapy.

Left Ventricle Outflow Tract Velocity-Time Index and Right Ventricle to Left Ventricle Ratio as Predictors for in Hospital Outcome in Intermediate-Risk Pulmonary Embolism.

Accurate estimation of risk with both imaging and biochemical parameters in intermediate risk pulmonary embolism (PE) remains challenging. The aim of the study was to evaluate echocardiographic parameters that reflect right and left heart hemodynamic as predictors of adverse events in intermediate risk PE. This was a retrospective observational study on patients with computed tomography pulmonary angiography diagnosis of PE admitted at Cardiology department of the Clinical Emergency Hospital of Oradea, Romania between January 2018­December 2021. Echocardiographic parameters obtained at admission were studied as predictors of in hospital adverse events. The following adverse outcomes were registered: death, resuscitated cardiac arrest, hemodynamic deterioration and need of rescue thrombolysis. An adverse outcome was present in 50 patients (12.62%). PE related death was registered in 17 patients (4.3%), resuscitated cardiac arrest occurred in 6 patients (1.51%). Another 20 patients (5.05%) required escalation of therapy with thrombolysis and 7 (1.76%) patients developed haemodynamic instability. Echocardiographic independent predictors for in hospital adverse outcome were RV/LV ≥ 1 (HR = 3.599, 95% CI 1.378−9.400, p = 0.009) and VTI ≤ 15 mm (HR = 11.711, 95% CI 4.336−31.633, p < 0.001). The receiver operator curve renders an area under curve for LVOT VTI ≤ 15 mm of 0.792 (95% CI 0.719−0.864, p < 0.001) and for a RV/LV ≥ 1 of 0.746 (95% CI 0.671−0.821, p < 0.001). A combined criterion (LVOT VTI ≤ 15 and RV/LV ≥ 1) showed a positive predictive value of 75% and a negative predictive value of 95% regarding in hospital adverse outcomes. Low LVOT VTI and increased RV/LV are useful for identifying normotensive patients with PE at risk for short term adverse outcomes. Combining an LVOT VTI ≤ 15 cm with a RV/LV ≥ 1 can identify with increased accuracy PE patients with impending risk of clinical deterioration.

Use of anticoagulant drugs in patients with atrial fibrillation. Does adherence to therapy have a prognostic impact?

Anticoagulant therapy represents a pivotal element that strongly influences the thromboembolic risk of non-valvular atrial fibrillation (NVAF) subjects. The main purpose of this review was to identify issues and suggest strategies to improve the oral anticoagulants (OACs) treatment adherence, which is the most important predictor of NVAF outcome. Advantages, efficacy, and impact of these drugs on patients' prognosis were revealed in important clinical trials on large cohorts of patients and are often prescribed nowadays. A real-life data registry, the Global Anticoagulant Registry in the Field-Atrial Fibrillation (GARFIELD-AF) analyzed the profile and outcome of patients diagnosed with NVAF receiving oral antithrombotic treatment. The observations gathered in the registry were crucial for identifying relevant elements that clinicians must improve, such as adherence strategies and predisposing factors that correlated with stroke. Adherence to OACs in AF patients is essential from the viewpoint of clinical efficacy and safety. Major adverse events and negative outcome are correlated with a weak anticoagulation control caused by an ineffective treatment adherence strategy. Solving the issue of oral anticoagulation adherence is possible using new technologies, but future directions should be explored. Mobile phone applications centered on patients' needs, telemedicine programs that evaluate patients' evolution and detect adverse reactions or events, encouraging an adequate management of the event without interruption of OACs, represent perspectives with a major impact on treatment adherence.

Analysis of the Impact of Comorbidities on Endometrial Lesions Using the Charlson Comorbidity Index in Western Romania.

Background and Objectives: This retrospective study aimed to identify the main comorbidities found in gynecological patients hospitalized for endometrial lesions and to analyze the relationships between these comorbidities and each type of endometrial lesion. The Charlson comorbidity index (CCI) was calculated, thus assessing the patient's probability of survival in relation to the underlying disease and the existing comorbidities. Materials and Methods: During 2015-2019, 594 cases hospitalized for vaginal bleeding outside of pregnancy were included in the research. For all cases, the frequency of comorbidities was calculated, applying the Cox proportional hazard model, considering the hospitalizations (from the following year after the first outpatient or hospital assessment) as a dependent variable; age and comorbidities were considered as independent variables. Results: Analysis of variance (ANOVA) for mean age of patients enrolled after diagnosis and multiple comparisons (via the Tukey post-hoc test) indicate significant differences (p < 0.05) between the average age for endometrial cancer (EC) and that for the typical endometrial hyperplasia or other diagnoses. The most common comorbidities were hypertension (62.28%), obesity (35.01%), and diabetes (22.89%), followed by cardiovascular disease. An intensely negative correlation (r = -0.715281634) was obtained between the percentage values of comorbidities present in EC and other endometrial lesions. The lowest chances of survival were calculated for 88 (14.81% of the total) patients over 50 years (the probability of survival in the next 10 years being between 0 and 21%). The chances of survival at 10 years are moderately negatively correlated with age (sample size = 594, r = -0.6706, p < 0.0001, 95% confidence interval (CI) for r having values from -0.7126 to -0.6238) and strongly negatively correlated with the CCI (r = -0.9359, p < 0.0001, 95% CI for r being in the range -0.9452 to -0.9251). Conclusions: Using CCI in endometrial lesions is necessary to compare the estimated risk of EC mortality with other medical conditions.

The Correlation of the IETA Ultrasound Score with the Histopathology Results for Women with Abnormal Bleeding in Western Romania.

In the early differential diagnosis of endometrial cancer (EC), decisive and mandatory histological aspects are considered, in addition to obvious clinical manifestations. In addition, sonographic aspects are characteristic in relation to the stage, degree, and histological types of identified cancer. This bi-center retrospective observational study included 594 women with abnormal uterine bleeding outside pregnancy, for which a biopsy was performed in the Obstetrics and Gynecology Departments of the Emergency County Hospitals of Arad and Timis Counties, Romania, between 2015 and 2019. Most of the cases were represented by EC or endometrial hyperplasia (EH). Of the 594 cases, 25.5% (n = 153) were EC at women aged between 41 and 85 years. High International Endometrial Tumor Analysis (IETA) scores (3, 4) were associated with a relative risk of 2.9335 compared with other endometrial lesions (95% CI 2.3046 to 3.734, p < 0.0001, NNT 1.805). Histological aspects and pelvic ultrasound using IETA scores represent valuable noninvasive assets in diagnosing and differentiating endometrial cancer from benign uterine pathology.

Framing Cause-Effect Relationship of Acute Coronary Syndrome in Patients with Chronic Kidney Disease.

The main causes of death in patients with chronic kidney disease (CKD) are of cardiovascular nature. The interaction between traditional cardiovascular risk factors (CVRF) and non-traditional risk factors (RF) triggers various complex pathophysiological mechanisms that will lead to accelerated atherosclerosis in the context of decreased renal function. In terms of mortality, CKD should be considered equivalent to ischemic coronary artery disease (CAD) and properly monitored. Vascular calcification, endothelial dysfunction, oxidative stress, anemia, and inflammatory syndrome represents the main uremic RF triggered by accumulation of the uremic toxins in CKD subjects. Proteinuria that appears due to kidney function decline may initiate an inflammatory status and alteration of the coagulation-fibrinolysis systems, favorizing acute coronary syndromes (ACS) occurrence. All these factors represent potential targets for future therapy that may improve CKD patient's survival and prevention of CV events. Once installed, the CAD in CKD population is associated with negative outcome and increased mortality rate, that is the reason why discovering the complex pathophysiological connections between the two conditions and a proper control of the uremic RF are crucial and may represent the solutions for influencing the prognostic. Exclusion of CKD subjects from the important trials dealing with ACS and improper use of the therapeutical options because of the declined kidney functioned are issues that need to be surpassed. New ongoing trials with CKD subjects and platelets reactivity studies offers new perspectives for a better clinical approach and the expected results will clarify many aspects.

The Footprint of Kynurenine Pathway in Neurodegeneration: Janus-Faced Role in Parkinson's Disorder and Therapeutic Implications.

Progressive degeneration of neurons and aggravation of dopaminergic neurons in the substantia nigra pars compacta results in the loss of dopamine in the brain of Parkinson's disease (PD) patients. Numerous therapies, exhibiting transient efficacy have been developed; however, they are mostly accompanied by side effects and limited reliability, therefore instigating the need to develop novel optimistic treatment targets. Significant therapeutic targets have been identified, namely: chaperones, protein Abelson, glucocerebrosidase-1, calcium, neuromelanin, ubiquitin-proteasome system, neuroinflammation, mitochondrial dysfunction, and the kynurenine pathway (KP). The role of KP and its metabolites and enzymes in PD, namely quinolinic acid (QUIN), kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK), 3-hydroxyanthranillic acid (3-HAA), kunurenine-3-monooxygenase (KMO), etc. has been reported. The neurotoxic QUIN, N-methyl-D-aspartate (NMDA) receptor agonist, and neuroprotective KYNA-which antagonizes QUIN actions-primarily justify the Janus-faced role of KP in PD. Moreover, KP has been reported to play a biomarker role in PD detection. Therefore, the authors detail the neurotoxic, neuroprotective, and immunomodulatory neuroactive components, alongside the upstream and downstream metabolic pathways of KP, forming a basis for a therapeutic paradigm of the disease while recognizing KP as a potential biomarker in PD, thus facilitating the development of a suitable target in PD management.

Role of Monoamine Oxidase Activity in Alzheimer's Disease: An Insight into the Therapeutic Potential of Inhibitors.

Despite not being utilized as considerably as other antidepressants in the therapy of depression, the monoamine oxidase inhibitors (MAOIs) proceed to hold a place in neurodegeneration and to have a somewhat broad spectrum in respect of the treatment of neurological and psychiatric conditions. Preclinical and clinical studies on MAOIs have been developing in recent times, especially on account of rousing discoveries manifesting that these drugs possess neuroprotective activities. The altered brain levels of monoamine neurotransmitters due to monoamine oxidase (MAO) are directly associated with various neuropsychiatric conditions like Alzheimer's disease (AD). Activated MAO induces the amyloid-beta (Aß) deposition via abnormal cleavage of the amyloid precursor protein (APP). Additionally, activated MAO contributes to the generation of neurofibrillary tangles and cognitive impairment due to neuronal loss. No matter the attention of researchers on the participation of MAOIs in neuroprotection has been on monoamine oxidase-B (MAO-B) inhibitors, there is a developing frame of proof indicating that monoamine oxidase-A (MAO-A) inhibitors may also play a role in neuroprotection. The therapeutic potential of MAOIs alongside the complete understanding of the enzyme's physiology may lead to the future advancement of these drugs.

Highlighting the Relevance of Gut Microbiota Manipulation in Inflammatory Bowel Disease.

Two different conditions are included in inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC), being distinguished by chronic recurrence of gut inflammation in persons that are genetically predisposed and subjected to environmental causative factors. The normal structure of the gut microbiome and its alterations in IBD were defined in several microbial studies. An important factor in the prolonged inflammatory process in IBD is the impaired microbiome or "dysbiosis". Thus, gut microbiome management is likely to be an objective in IBD treatment. In this review, we analyzed the existing data regarding the pathophysiological/therapeutic implications of intestinal microflora in the development and evolution of IBD. Furthermore, the main effects generated by the administration of probiotics, prebiotics, fecal transplantation, and phytochemicals supplementation were analyzed regarding their potential roles in improving the clinical and biochemical status of patients suffering from Crohn's disease (CD) and ulcerative colitis (UC), and are depicted in the sections/subsections of the present paper. Data from the literature give evidence in support of probiotic and prebiotic therapy, showing effects such as improving remission rate, improving macroscopic and microscopic aspects of IBD, reducing the pro-inflammatory cytokines and interleukins, and improving the disease activity index. Therefore, the additional benefits of these therapies should not be ignored as adjuvants to medical therapy.

Current Perspective on the Natural Compounds and Drug Delivery Techniques in Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is one of the debilitating brain tumors, being associated with extremely poor prognosis and short median patient survival. GBM is associated with complex pathogenesis with alterations in various cellular signaling events, that participate in cell proliferation and survival. The impairment in cellular redox pathways leads to tumorigenesis. The current standard pharmacological regimen available for glioblastomas, such as radiotherapy and surgical resection following treatment with chemotherapeutic drug temozolomide, remains fatal, due to drug resistance, metastasis and tumor recurrence. Thus, the demand for an effective therapeutic strategy for GBM remains elusive. Hopefully, novel products from natural compounds are suggested as possible solutions. They protect glial cells by reducing oxidative stress and neuroinflammation, inhibiting proliferation, inducing apoptosis, inhibiting pro-oncogene events and intensifying the potent anti-tumor therapies. Targeting aberrant cellular pathways in the amelioration of GBM could promote the development of new therapeutic options that improve patient quality of life and extend survival. Consequently, our review emphasizes several natural compounds in GBM treatment. We also assessed the potential of drug delivery techniques such as nanoparticles, Gliadel wafers and drug delivery using cellular carriers which could lead to a novel path for the obliteration of GBM.

Bioinformatics Accelerates the Major Tetrad: A Real Boost for the Pharmaceutical Industry.

With advanced technology and its development, bioinformatics is one of the avant-garde fields that has managed to make amazing progress in the pharmaceutical-medical field by modeling the infrastructural dimensions of healthcare and integrating computing tools in drug innovation, facilitating prevention, detection/more accurate diagnosis, and treatment of disorders, while saving time and money. By association, bioinformatics and pharmacovigilance promoted both sample analyzes and interpretation of drug side effects, also focusing on drug discovery and development (DDD), in which systems biology, a personalized approach, and drug repositioning were considered together with translational medicine. The role of bioinformatics has been highlighted in DDD, proteomics, genetics, modeling, miRNA discovery and assessment, and clinical genome sequencing. The authors have collated significant data from the most known online databases and publishers, also narrowing the diversified applications, in order to target four major areas (tetrad): DDD, anti-microbial research, genomic sequencing, and miRNA research and its significance in the management of current pandemic context. Our analysis aims to provide optimal data in the field by stratification of the information related to the published data in key sectors and to capture the attention of researchers interested in bioinformatics, a field that has succeeded in advancing the healthcare paradigm by introducing developing techniques and multiple database platforms, addressed in the manuscript.

Value of Hematological and Coagulation Parameters as Prognostic Factors in Acute Coronary Syndromes.

The values of hematological and coagulation biomarkers were evaluated as predictors of in hospital mortality and complications, in patients with acute coronary syndromes (ACS). This retrospective observational study enrolled 936 ACS subjects admitted to the Clinical Emergency Hospital of Oradea, Romania, between January-December 2019. Hematological and coagulation parameters were obtained at admission. During hospitalization, the following adverse events were recorded: death, ventricular rhythm disturbances, atrial fibrillation, heart failure, re-infarction, and stroke. Accuracy of hematological and coagulation parameters as predictors of adverse outcome were also evaluated. The diagnosis was unstable angina in 442 patients (47.22%), non-ST-elevation myocardial infarction (NSTEMI) in 113 patients (12.1%) and ST-elevation myocardial infarction (STEMI) in 381 patients (40.70%); 87 patients (9.29%) died during hospitalization and 193 (20.7%) developed complications. Predictors for in hospital mortality were as follows: red cell distribution width (RDW) (AUC 0.691, p < 0.0001), white blood cells (WBC) (AUC 0.684, p < 0.0001), neutrophils (NEU) (AUC 0.684, p < 0.0001), and prothrombin time (PT) (AUC 0.765, p < 0.0001). WBC (AUC 0.659, p < 0.0001), NEU (AUC 0.664, p < 0.0001), RDW (AUC 0.669, p < 0.0001), and PT (AUC 0.669, 95% CI 0.622-0.714, p < 0.0001) also had accuracy for complications prediction. RDW had a good ability to predict heart failure in NSTEMI patients (AUC 0.832, p < 0.0001). An acceptable ability to predict ventricular rhythm disturbances occurrence had WBC (AUC 0.758, p < 0.0001) and NEU (AUC 0.772, p < 0.0001). Hematological and coagulation parameters can help in risk stratification of ACS patients. RDW, WBC, NEU, and PT were able to predict mortality and in-hospital complications in ACS patients. RDW has a good accuracy in predicting complications and heart failure in NSTEMI patients. WBC and NEU are good predictors for ventricular rhythm disturbances.

Recognizing the Benefits of Pre-/Probiotics in Metabolic Syndrome and Type 2 Diabetes Mellitus Considering the Influence of Akkermansia muciniphila as a Key Gut Bacterium.

Metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) are diseases that can be influenced by the structure of gut microbiota, whose improvement is often neglected in metabolic pathology. This review highlights the following main aspects: the relationship between probiotics/gut microbes with the pathogenesis of MetS, the particular positive roles of Akkermansia muciniphila supplementation in the onset of MetS, and the interaction between dietary polyphenols (prebiotics) with gut microbiota. Therefore, an extensive and in-depth analysis of the often-neglected correlation between gut microbiota and chronic metabolic diseases was conducted, considering that this topic continues to fascinate and stimulate researchers through the discovery of novel strains and their beneficial properties.

Social and Neurocognitive Deficits in Remitted Patients with Schizophrenia, Schizoaffective and Bipolar Disorder.

This study assesses the empathy level, cognitive performance and emotion recognition skills of remitted patients with schizophrenia, schizoaffective disorder and bipolar disorder, and also explores the relationship between impairments in the mentioned domains. The study was performed on 77 subjects divided into two groups: PAT sample (N = 37) included remitted patients with either schizophrenia, schizoaffective or bipolar disorder who were compared with healthy control subjects from the HC sample (N = 40). Along with sociodemographic and clinical data, empathy levels (using EQ (Empathy Quotient) scale), the ability to recognize another person's emotional state (using RMET (Reading the Mind in the Eyes Test)), and cognitive performance (using MoCA (Montreal Cognitive Assessment) Scale) were investigated. The intensity of the psychiatric symptoms was measured with BPRS-E (Brief Psychiatric Rating Scale-Expanded). The remitted patients had lower EQ (p = 0.02) and RMET (p < 0.0001) scores than the healthy subjects. In the PAT group, RMET scores were positively correlated with MoCA total scores. Both EQ and RMET scores were negatively correlated with BPRS-E total scores. Psychiatric disorder was a significant predictor for deficits in emotion recognition. There were no significant differences in RMET, EQ and MoCA scores between patients with respect to diagnosis, the type of antipsychotic or the associated medication. In both samples, females had higher empathy levels (p = 0.04) and better emotion recognition abilities (p = 0.04) than males. Patients with schizophrenia, schizoaffective or bipolar disorder, currently in remission, displayed lower empathy levels and poorer emotion recognition skills than healthy subjects. Poor emotion recognition skills were associated with symptom severity and impairments in global cognition.

Non-Alcoholic Fatty Liver Disease and Cardiovascular Comorbidities: Pathophysiological Links, Diagnosis, and Therapeutic Management.

Non-alcoholic fatty liver disease (NAFLD) has a growing prevalence in recent years. Its association with cardiovascular disease has been intensively studied, and certain correlations have been identified. The connection between these two entities has lately aroused interest regarding therapeutic management. In order to find the best therapeutic options, a detailed understanding of the pathophysiology that links (NAFLD) to cardiovascular comorbidities is needed. This review focuses on the pathogenic mechanisms that are behind these two diseases and on the therapeutic management available at this time.