The Molecular Mechanisms Underlying the Systemic Effects Mediated by Parathormone in the Context of Chronic Kidney Disease.

Chronic kidney disease (CKD) stands as a prominent non-communicable ailment, significantly impacting life expectancy. Physiopathology stands mainly upon the triangle represented by parathormone-Vitamin D-Fibroblast Growth Factor-23. Parathormone (PTH), the key hormone in mineral homeostasis, is one of the less easily modifiable parameters in CKD; however, it stands as a significant marker for assessing the risk of complications. The updated "trade-off hypothesis" reveals that levels of PTH spike out of the normal range as early as stage G2 CKD, advancing it as a possible determinant of systemic damage. The present review aims to review the effects exhibited by PTH on several organs while linking the molecular mechanisms to the observed actions in the context of CKD. From a diagnostic perspective, PTH is the most reliable and accessible biochemical marker in CKD, but its trend bears a higher significance on a patient's prognosis rather than the absolute value. Classically, PTH acts in a dichotomous manner on bone tissue, maintaining a balance between formation and resorption. Under the uremic conditions of advanced CKD, the altered intestinal microbiota majorly tips the balance towards bone lysis. Probiotic treatment has proven reliable in animal models, but in humans, data are limited. Regarding bone status, persistently high levels of PTH determine a reduction in mineral density and a concurrent increase in fracture risk. Pharmacological manipulation of serum PTH requires appropriate patient selection and monitoring since dangerously low levels of PTH may completely inhibit bone turnover. Moreover, the altered mineral balance extends to the cardiovascular system, promoting vascular calcifications. Lastly, the involvement of PTH in the Renin-Angiotensin-Aldosterone axis highlights the importance of opting for the appropriate pharmacological agent should hypertension develop.

Trauma Outcomes in Pediatric Nonfatal Road Traffic Accidents.

BACKGROUND: By 2025, road traffic injuries are projected to rank third in the global burden of disease, posing a significant challenge that affects health, social well-being, and economic aspects. According to data from the Romanian Police National Statistics Center, there have been an average of 342 traffic accidents per year involving pediatric patients over the past 10 years. MATERIALS AND METHODS: A retrospective research study was conducted, encompassing 358 cases of road traffic accidents identified for the study, with data collected over a span of eight years, and with the aim of analyzing the types of injury and treatment methods in relation to age and sex, while also focusing on the duration of hospitalization and the occurrence of complications. RESULTS: An oscillating trend is observed from 2015 to 2020, with its lowest value recorded in 2017 at around 6.8% and its peak in 2019 at 20.1%. Notably, post-pandemic (COVID-19), the cases underwent a substantial decline of approximately 60%. At least 78.7% of those who did not undergo orthopedic reduction required surgery, whereas among those who underwent orthopedic reduction, only 23.4% needed surgery. Regarding the frequency of complications 17.3% of the total cases experienced complications. CONCLUSIONS: According to our findings, age has a significant effect on the type of accident (p < 0.05). Complications occurred in 17.3% of patients, most commonly surgical (24 cases, 38.7%), orthopedic (17 cases, 27.4%), and neurological (15 cases, 24.2%).

Traffic Accidents in Children and Adolescents: A Complex Orthopedic and Medico-Legal Approach.

Traffic accidents involving children and adolescents present complex challenges from both the medico-legal and orthopedic standpoints. Despite the implementation of road traffic safety laws, pediatric road traffic injuries continue to be a significant contributor to mortality rates, physical harm, and hospitalization on a global scale. For children and young people, automobile accidents are considered to be the primary culprit of mortality in developed nations. Even in highly developed nations, trauma is a significant factor in infant mortality. Each age category, from childhood to young adulthood, has its fracture patterns, as their skeletons are considerably different from those of adults. The consequences of traffic accidents extend beyond the immediate physical trauma. The medico-legal aspects surrounding these incidents add another layer of complexity, as legal repercussions may affect the responsible adult or parent, particularly in cases involving child fatalities. To effectively address traffic accidents in children and adolescents, a comprehensive approach is necessary. This approach should involve not only medical professionals but also legal experts and policymakers. Collaboration between orthopedic specialists, medico-legal professionals, law enforcement agencies, and relevant government bodies can facilitate the development and implementation of strategies aimed at prevention, education, the enforcement of traffic laws, and improved infrastructure. By addressing both the medical and legal aspects, it is possible to enhance road safety for children and adolescents, reducing the incidence of injuries and their associated long-term consequences. In this review, we aimed to summarize traffic accidents in children and adolescents from a complex orthopedic and medico-legal approach.

Current Epidemiological Trends of Pediatric Traffic Accidents at a Romanian Clinical Hospital.

BACKGROUND: Pediatric road traffic accidents (RTAs) have a substantial impact on the worldwide youth population, resulting in a considerable burden of disability. According to the World Health Organization's (WHO) Global Status Report on Road Safety, around 1.35 million children die each year in RTAs around the world, having a big effect on health and financial costs. Today's high-income countries like the Netherlands have experienced a decrease in the incidence of fatal traffic accidents (TAs) in children compared to countries with higher-than-average scores, including Romania, where roughly one out of every two minor deaths was a pedestrian; however, there is a lack of comprehensive and up-to-date epidemiological data on non-fatal TAs regarding pediatric patients. The objective of this study is to perform a thorough examination of the epidemiological aspects of Tas in pediatric patients admitted to the Emergency Department (ED) of "St. Mary's" Emergency Clinical Hospital for Children in Iasi, Romania. MATERIALS AND METHODS: A descriptive retrospective research study was conducted at the "St. Mary's" Emergency Clinical Hospital for Children in Iasi, Romania, from January 2015 to December 2022. The research population includes all pediatric trauma patients that were between the age range of 1 month and 18 years who were treated by the trauma department. A total of 358 cases met the inclusion criteria and fulfilled fulfilled fulfilled. Data concerning variables such as accident incidents, types of injuries, and length of hospitalization have been gathered. RESULTS: The average age of the patients was 11.43 ± 4.07 years, with patients of both sexes, the representation of the male sex being 78.5%. The incidence occurred during the summer, representing 15.3% in June. Of the patients admitted to the ED, 55.5% (n = 196) did not require surgery. Most of the patients spent from a minimum of one day to a maximum of 28 days in the hospital, with an average of 8.50 hospital days. The most common injuries were fractures (n = 221), and the most frequent anatomical region affected was the upper limbs (n = 55.2%). CONCLUSION: While the literature on fatal TA cases shows a declining trend, there is a lack of up-to-date information on non-fatal TAs involving children. The results of our study suggest that there is a high incidence of pediatric TAs due to the scale of "St. Mary's" Emergency Clinical Hospital for Children, from Iasi, which provides medical services to a considerable number of patients coming from both rural and urban areas of the seven counties of Moldova region, in Romania.

Brugada Syndrome: From Molecular Mechanisms and Genetics to Risk Stratification.

Brugada syndrome (BrS) is a rare hereditary arrhythmia disorder, with a distinctive ECG pattern, correlated with an increased risk of ventricular arrhythmias and sudden cardiac death (SCD) in young adults. BrS is a complex entity in terms of mechanisms, genetics, diagnosis, arrhythmia risk stratification, and management. The main electrophysiological mechanism of BrS requires further research, with prevailing theories centered on aberrant repolarization, depolarization, and current-load match. Computational modelling, pre-clinical, and clinical research show that BrS molecular anomalies result in excitation wavelength (k) modifications, which eventually increase the risk of arrhythmia. Although a mutation in the SCN5A (Sodium Voltage-Gated Channel Alpha Subunit 5) gene was first reported almost two decades ago, BrS is still currently regarded as a Mendelian condition inherited in an autosomal dominant manner with incomplete penetrance, despite the recent developments in the field of genetics and the latest hypothesis of additional inheritance pathways proposing a more complex mode of inheritance. In spite of the extensive use of the next-generation sequencing (NGS) technique with high coverage, genetics remains unexplained in a number of clinically confirmed cases. Except for the SCN5A which encodes the cardiac sodium channel NaV1.5, susceptibility genes remain mostly unidentified. The predominance of cardiac transcription factor loci suggests that transcriptional regulation is essential to the Brugada syndrome's pathogenesis. It appears that BrS is a multifactorial disease, which is influenced by several loci, each of which is affected by the environment. The primary challenge in individuals with a BrS type 1 ECG is to identify those who are at risk for sudden death, researchers propose the use of a multiparametric clinical and instrumental strategy for risk stratification. The aim of this review is to summarize the latest findings addressing the genetic architecture of BrS and to provide novel perspectives into its molecular underpinnings and novel models of risk stratification.

Pulmonary Embolism Risk Assessment Using Blood Copeptin Concentration and Pulmonary Arteries Thrombotic Burden Evaluated by Computer Tomography.

(1) Background: Pulmonary embolism (PE) represents the third most important cardiovascular cause of death after myocardial infarction and stroke. The proper management of this condition is dependent on adequate risk stratification, due to the life-threatening complications of more aggressive therapies such as thrombolysis. Copeptin is a surrogate marker of vasopressin which is found increased in several cardiovascular conditions. The Mastora score is an imagistic evaluation of the degree of pulmonary arteries thrombotic burden based on computed tomography angiography. In this study, we aimed to evaluate the diagnostic and prognostic role of copeptin in patients with acute PE. Furthermore, we analyzed the relationship between copeptin and Mastora score and their role in PE risk profiling. (2) Methods: We conducted a single center prospective study that included 112 patients with PE and 53 healthy volunteers. Clinical and paraclinical parameters, together with plasma levels of copeptin and the Mastora score, were evaluated in all patients after admission. (3) Results: Copeptin levels were significantly increased in PE patients compared with the general population (26.05 vs. 9.5 pmol/L, p < 0.001), while receiver operating characteristic (ROC) analysis revealed an AUC of 0.800 (95% CI 0.728−0.873, p < 0.001). Copeptin directly correlated with the Mastora score (r = 0.535, p = 0.011) and both parameters were strong predictors for adverse clinical events and death. Receiver operating characteristic (ROC) analysis for death within 30 days revealed a copeptin cut-off of 38.36 pmol/L, which presented a specificity of 79.6% and a sensitivity of 88.9%, and a Mastora score cut-off of 82 points, which presented a specificity of 74.8% and a sensitivity of 77.8%. (4) Conclusions: Our results showed that copeptin and the Mastora score are both correlated with adverse cardiovascular events and mortality in PE patients, and this may pave the way for their use in clinical practice, helping physicians to select the best therapeutical management.

Modern Approaches for the Treatment of Heart Failure: Recent Advances and Future Perspectives.

Heart failure (HF) is a progressively deteriorating medical condition that significantly reduces both the patients' life expectancy and quality of life. Even though real progress was made in the past decades in the discovery of novel pharmacological treatments for HF, the prevention of premature deaths has only been marginally alleviated. Despite the availability of a plethora of pharmaceutical approaches, proper management of HF is still challenging. Thus, a myriad of experimental and clinical studies focusing on the discovery of new and provocative underlying mechanisms of HF physiopathology pave the way for the development of novel HF therapeutic approaches. Furthermore, recent technological advances made possible the development of various interventional techniques and device-based approaches for the treatment of HF. Since many of these modern approaches interfere with various well-known pathological mechanisms in HF, they have a real ability to complement and or increase the efficiency of existing medications and thus improve the prognosis and survival rate of HF patients. Their promising and encouraging results reported to date compel the extension of heart failure treatment beyond the classical view. The aim of this review was to summarize modern approaches, new perspectives, and future directions for the treatment of HF.