A cutting-edge new framework for the pain management in children: nanotechnology.

Pain is a subjective concept which is ever-present in the medical field. Health professionals are confronted with a variety of pain types and sources, as well as the challenge of managing a patient with acute or chronic suffering. An even bigger challenge is presented in the pediatric population, which often cannot quantify pain in a numerical scale like adults. Infants and small children especially show their discomfort through behavioral and physiological indicators, leaving the health provider with the task of rating the pain. Depending on the pathophysiology of it, pain can be classified as neuropathic or nociceptive, with the first being defined by an irregular signal processing in the nervous system and the second appearing in cases of direct tissue damage or prolonged contact with a certain stimulant. The approach is generally either pharmacological or non-pharmacological and it can vary from using NSAIDs, local anesthetics, opiates to physical and psychological routes. Unfortunately, some pathologies involve either intense or chronic pain that cannot be managed with traditional methods. Recent studies have involved nanoparticles with special characteristics such as small dimension and large surface area that can facilitate carrying treatments to tissues and even offer intrinsic analgesic properties. Pediatrics has benefited significantly from the application of nanotechnology, which has enabled the development of novel strategies for drug delivery, disease diagnosis, and tissue engineering. This narrative review aims to evaluate the role of nanotechnology in current pain therapy, with emphasis on pain in children.

Identifying Childhood Risk Factors for Hepatitis B with a Focus on Vertical Transmission.

BACKGROUND: Despite worldwide vaccination efforts, Hepatitis B virus (HBV) infection remains a significant global health burden, particularly in regions where vertical transmission is prevalent. Given Romania's history as an endemic area for hepatitis B from the 1990s until the early 2000s and the previously high infection rates among children, it is crucial to continually evaluate HBV infection in this population to monitor current trends, assess the long-term impact of vaccination programs, and address any remaining gaps in prevention and treatment efforts. This study aims to identify childhood risk factors associated with HBV acquisition, examining the role of maternal HBV status in child HBV infection, focusing on vertical transmission among a cohort of 654 children, with maternal infection as the independent variable and child infection as the dependent variable. METHODS: We assessed potential risk factors and vaccination coverage among these children. The cohort included 148 children who tested positive for chronic hepatitis B from those 654 tested for HBsAg. Anamnestic data and vaccination history were analyzed, with particular attention to birth type and surgical interventions. RESULTS: Of the 148 HBV-positive children, 80.4% were delivered naturally. Among these, 130 had received hepatitis B vaccination, and 5 were also given hepatitis B immunoglobulin at birth, 4 of whom were born via cesarean section. In the control group, comprising 418 vaccinated children, a lesser proportion were unvaccinated (2.2%). Documented surgical interventions included general and dental surgeries, as well as a single blood transfusion. CONCLUSIONS: The study emphasizes the need for comprehensive vaccination strategies and illuminates potential correlations between birth type and vaccination status with childhood HBV infection. Crucially, it highlights the necessity of diligent monitoring and treatment of pregnant women with HBV to prevent vertical transmission as effectively as possible.

Triangular fossa of the third cerebral ventricle - an original 3D model and morphometric study.

Introduction: The triangular recess (TR), also called triangular fossa or vulva cerebri, represents the anterior extension of the diencephalic ventricle, located between the anterior columns of the fornix and the anterior white commissure. Over time, this structure of the third cerebral ventricle generated many disputes. While some anatomists support its presence, others have opposite opinions, considering that it only becomes visible under certain conditions. The aim of the study is to demonstrate the tangible structure of the triangular recess. Secondly, the quantitative analysis allowed us to establish an anatomical morphometric standard, as well as the deviations from the standard. Materials and methods: Our study is both a quantitative and a qualitative evaluation of the triangular fossa. We dissected 100 non-neurological adult brains, which were fixed in 10% formaldehyde solution for 10 weeks. The samples are part of the collection of the Institute of Anatomy, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi. We highlighted the triangular fossa by performing dissections in two stages at the level of the roof of the III ventricle. Results: The qualitative analysis is a re-evaluation of the classical data concerning the anatomy of the fossa triangularis. We proposed an original 3D model of the triangular recess in which we described a superficial part called vestibule and a deep part called pars profunda. We measured the sides of the communication between the two proposed segments, as well as the communication with the III ventricle. By applying the Heron's formula, we calculated the area of the two communications. Statistical evaluations have shown that these communications are higher than they are wide. In addition, there is a statistical difference between the surfaces of the two communications: 34.07 mm2 ± 7.01 vs. 271.43 mm2 ± 46.36 (p = 0.001). Conclusion: The outcome of our study is both qualitative and quantitative. Firstly, we demonstrated the existence of the triangular fossa and we conceived a spatial division of this structure. Secondly, the measurements carried out establish an anatomo-morphometric norm of the triangular recess, which is useful in assessing the degree of hydrocephalus during the third endoscopic ventriculoscopy.

Is oxidative stress - antioxidants imbalance the physiopathogenic core in pediatric obesity?

Despite the early recognition of obesity as an epidemic with global implications, research on its pathogenesis and therapeutic approach is still on the rise. The literature of the 21st century records an excess weight found in up to 1/3 of children. Both the determining factors and its systemic effects are multiple and variable. Regarding its involvement in the potentiation of cardio-vascular, pulmonary, digestive, metabolic, neuro-psychic or even dermatological diseases, the information is already broadly outlined. The connection between the underlying disease and the associated comorbidities seems to be partially attributable to oxidative stress. In addition to these, and in the light of the recent COVID-19 pandemic, the role played by oxidative stress in the induction, maintenance and potentiation of chronic inflammation among overweight children and adolescents becomes a topic of interest again. Thus, this review's purpose is to update general data on obesity, with an emphasis on the physiopathological mechanisms that underlie it and involve oxidative stress. At the same time, we briefly present the latest principles of pathology diagnosis and management. Among these, we will mainly emphasize the impact played by endogenous and exogenous antioxidants in the evolutionary course of pediatric obesity. In order to achieve our objectives, we will refer to the most recent studies published in the specialized literature.

Insights into the Natural and Treatment Courses of Hepatitis B in Children: A Retrospective Study.

Chronic Hepatitis B virus (HBV) infection in children remains a significant public health challenge. The natural history and treatment outcomes of HBV can vary widely, influencing management strategies. This retrospective study was conducted in Northeast Romania and involved a cohort of 148 pediatric patients diagnosed with chronic viral Hepatitis B. Of these, 59 children underwent antiviral treatment while 89 were not treated. One of the main objectives was the rate of HBeAg (Hepatitis B-e antigen) seroconversion, a marker of disease progression and response to therapy. Among the treated group, 26 children (44%) achieved HBeAg seroconversion following therapy. In contrast, 44 of the untreated children (49%) experienced spontaneous HBeAg seroconversion, indicating a substantial rate of natural resolution within this population subset. The findings highlight a significant proportion of spontaneous seroconversion in untreated pediatric patients, suggesting a potential re-evaluation of treatment criteria and timing for children with chronic HBV infection. The comparable rates of seroconversion between treated and untreated cohorts underscore the need for individualized treatment approaches based on a combination of virological, biochemical, and clinical parameters. Further studies are required to refine management strategies to optimize long-term outcomes in pediatric HBV infections.

Pediatric Perspectives on Liver Cirrhosis: Unravelling Clinical Patterns and Therapeutic Challenges.

Background: Liver cirrhosis presents significant challenges in the pediatric population due to a complex interplay of etiological factors, clinical manifestations, and limited therapeutic options. The leading contributors to cirrhosis among pediatric patients are chronic cholestasis, metabolic disorders present from birth, and long-term hepatitis. Materials and method: Our narrative review aimed to synthesize literature data on the etiology, clinical picture, diagnostic techniques, optimal management of complications, and timely transplantation. Results: The epidemiology of liver cirrhosis in pediatric patients is evolving. The introduction of a universal vaccination and effective long-term viral suppression in viral hepatitis have significantly decreased complications rates. Liver transplantation programs worldwide have also improved the management of cirrhosis complications. Conclusions: Early diagnosis, comprehensive management strategies, and advancements in treatment modalities are critical for improving outcomes. Understanding these differences is crucial in providing age-appropriate care and support for those affected by cirrhosis.

Undercover lung damage in pediatrics - a hot spot in morbidity caused by collagenoses.

Connective tissue represents the support matrix and the connection between tissues and organs. In its composition, collagen, the major structural protein, is the main component of the skin, bones, tendons and ligaments. Especially at the pediatric age, its damage in the context of pathologies such as systemic lupus erythematosus, scleroderma or dermatomyositis can have a significant negative impact on the development and optimal functioning of the body. The consequences can extend to various structures (e.g., joints, skin, eyes, lungs, heart, kidneys). Of these, we retain and reveal later in our manuscript, mainly the respiratory involvement. Manifested in various forms that can damage the chest wall, pleura, interstitium or vascularization, lung damage in pediatric systemic inflammatory diseases is underdeveloped in the literature compared to that described in adults. Under the threat of severe evolution, sometimes rapidly progressive and leading to death, it is necessary to increase the popularization of information aimed at physiopathological triggering and maintenance mechanisms, diagnostic means, and therapeutic directions among medical specialists. In addition, we emphasize the need for interdisciplinary collaboration, especially between pediatricians, rheumatologists, infectious disease specialists, pulmonologists, and immunologists. Through our narrative review we aimed to bring up to date, in a concise and easy to assimilate, general principles regarding the pulmonary impact of collagenoses using the most recent articles published in international libraries, duplicated by previous articles, of reference for the targeted pathologies.

Pediatric endocarditis - a stone left after the pandemic cascade.

Infective endocarditis is a rare disease in children. The etiology is mainly bacterial. However, viral infective endocarditis, possibly related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has also been reported. The pathophysiological principle of the connection between the two entities seems to be attributed to the transient immune deficiency of the body during the infection. Additionally, SARS-CoV-2 is reported in the literature as a direct cardiopathic virus. Therefore, the new coronavirus seems to have the ability to affect both the intact cardiac tissue and the previously damaged one both during the acute episode and at a distance from it. Consequently, we propose to review the main pathophysiological aspects of pediatric cardiac damage caused by SARS-CoV-2. The ultimate goal is to deepen existing knowledge, broaden the horizon of understanding and analysis regarding the systemic damage induced by viral infections, and strengthen an information base from which to start a meta-analysis. Next, we performed a non-systematized screening of the specialized literature with reference to cases of endocarditis in the pediatric population, reported in the period 2020-2023. From the total of articles found, we chose to include in the review a number of 6 case reports, including a number of 7 patients (5 children and 2 adolescents). Analysis of reports suggests that SARS-CoV-2 infection could play a role in the development of endocarditis, either directly through active infection or indirectly through a post-infectious immune response. Also, pre-existing conditions and complex medical history predispose to an increased risk of developing a severe, complicated form of endocarditis. Also, the lack of data on the vaccination history and the failure to categorize the infection depending on the type of antibodies (IgM or IgG) in some studies represent a major bias in the reports. The latter make it difficult to evaluate the influence of vaccination and the impact of acute versus chronic infection on the course of cases.

Lung microbiome: new insights into bronchiectasis' outcome.

The present treatments for bronchiectasis, which is defined by pathological dilatation of the airways, are confined to symptom relief and minimizing exacerbations. The condition is becoming more common worldwide. Since the disease's pathophysiology is not entirely well understood, developing novel treatments is critically important. The interplay of chronic infection, inflammation, and compromised mucociliary clearance, which results in structural alterations and the emergence of new infection, is most likely responsible for the progression of bronchiectasis. Other than treating bronchiectasis caused by cystic fibrosis, there are no approved treatments. Understanding the involvement of the microbiome in this disease is crucial, the microbiome is defined as the collective genetic material of all bacteria in an environment. In clinical practice, bacteria in the lungs have been studied using cultures; however, in recent years, researchers use next-generation sequencing methods, such as 16S rRNA sequencing. Although the microbiome in bronchiectasis has not been entirely investigated, what is known about it suggests that Haemophilus, Pseudomonas and Streptococcus dominate the lung bacterial ecosystems, they present significant intraindividual stability and interindividual heterogeneity. Pseudomonas and Haemophilus-dominated microbiomes have been linked to more severe diseases and frequent exacerbations, however additional research is required to fully comprehend the role of microbiome in the evolution of bronchiectasis. This review discusses recent findings on the lung microbiota and its association with bronchiectasis.

Congenital Hyperinsulinism Caused by Mutations in ABCC8 Gene Associated with Early-Onset Neonatal Hypoglycemia: Genetic Heterogeneity Correlated with Phenotypic Variability.

Congenital hyperinsulinism (CHI) is a rare disorder of glucose metabolism and is the most common cause of severe and persistent hypoglycemia (hyperinsulinemic hypoglycemia, HH) in the neonatal period and childhood. Most cases are caused by mutations in the ABCC8 and KCNJ11 genes that encode the ATP-sensitive potassium channel (KATP). We present the correlation between genetic heterogeneity and the variable phenotype in patients with early-onset HH caused by ABCC8 gene mutations. In the first patient, who presented persistent severe hypoglycemia since the first day of life, molecular genetic testing revealed the presence of a homozygous mutation in the ABCC8 gene [deletion in the ABCC8 gene c.(2390+1_2391-1)_(3329+1_3330-1)del] that correlated with a diffuse form of hyperinsulinism (the parents being healthy heterozygous carriers). In the second patient, the onset was on the third day of life with severe hypoglycemia, and genetic testing identified a heterozygous mutation in the ABCC8 gene c.1792C>T (p.Arg598*) inherited on the paternal line, which led to the diagnosis of the focal form of hyperinsulinism. To locate the focal lesions, (18)F-DOPA (3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine) positron emission tomography/computed tomography (PET/CT) was recommended (an investigation that cannot be carried out in the country), but the parents refused to carry out the investigation abroad. In this case, early surgical treatment could have been curative. In addition, the second child also presented secondary adrenal insufficiency requiring replacement therapy. At the same time, she developed early recurrent seizures that required antiepileptic treatment. We emphasize the importance of molecular genetic testing for diagnosis, management and genetic counseling in patients with HH.

The role of vitamin D in pediatric systemic lupus erythematosus - a double pawn in the immune and microbial balance.

Having increased popularity during the Covid-19 pandemic, vitamin D3 is currently impressing thanks to the numerous researches aimed at its interactions with the body's homeostasis. At the same time, there is a peak in terms of recommendations for supplementation with it. Some of the studies focus on the link between autoimmune diseases and nutritional deficiencies, especially vitamin D3. Since the specialized literature aimed at children (patients between 0-18 years old) is far from equal to the informational diversity of the adult-centered branch, this review aims to bring up to date the relationship between the microbial and nutritional balance and the activity of pediatric systemic lupus erythematosus (pSLE). The desired practical purpose resides in a better understanding and an adequate, individualized management of the affected persons to reduce morbidity. The center of the summary is to establish the impact of hypovitaminosis D in the development and evolution of pediatric lupus erythematosus. We will address aspects related to the two entities of the impact played by vitamin D3 in the pathophysiological cascade of lupus, but also the risk of toxicity and its effects when the deficiency is over supplemented (hypervitaminosis D). We will debate the relationship of hypovitaminosis D with the modulation of immune function, the potentiation of inflammatory processes, the increase of oxidative stress, the perfusion of cognitive brain areas, the seasonal incidence of SLE and its severity. Finally, we review current knowledge, post-pandemic, regarding the hypovitaminosis D - pSLE relationship.

Celiac disease - a pluripathological model in pediatric practice.

Being defined as an autoimmune, chronic pathology, frequently encountered in any age group, but especially in pediatrics, celiac disease (also called gluten enteropathy), is gaining more and more ground in terms of diagnosis, but also interest in research. The data from the literature of the last decades attest the chameleonic way of its presentation, there may be both classic onset symptoms and atypical symptoms. Given the impact played by celiac disease, especially in the optimal growth and development of children, the current narrative review aims to highlight the atypical presentation methods, intended to guide the clinician towards the inclusion of the pathology in the differential diagnosis scheme. To these we add the summary presentation of the general data and therapeutic lines regarding the underlying condition and the existing comorbidities. In order to place the related information up to date, we performed a literature review of the recent articles published in international databases. We bring forward the current theories and approaches regarding both classic celiac disease and its atypical manifestations. Among these we note mainly constitutional, skin or mucous, bone, neuro-psychic, renal, reproductive injuries, but also disorders of biological constants and association with multiple autoimmunities. Knowing and correlating them with celiac disease is the key to optimal management of patients, thus reducing the subsequent burden of the disease.

Cystic fibrosis management in pediatric population-from clinical features to personalized therapy.

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). In 1949, it's been identified as a monogenic disease and was thought to primarily affect individuals of Northern European descent. It was the most prevalent autosomal recessive disease that shortens life. With the availability of multiple testing methodologies nowadays, there is a chance to create novel and enhanced treatment options. Even in the absence of a high sweat chloride test (SCT) result, the discovery of two causal mutations is diagnostic for cystic fibrosis (CF). For a CF diagnosis, however, at least two positive E sweat chloride tests are still required. In order to achieve early and active intervention to manage cystic fibrosis (CF) and its comorbidities, treatment regimens for pediatric patients should be evaluated, improved, and closely monitored. New developments in the treatment of cystic fibrosis (CF) have led to the development of medications derived from molecules that target the pathogenetic pathway of the illness. These options are very efficient and allow pediatric patients to receive individualized care. However, in order to better direct patient care and enhance patient outcomes, it is crucial to research uncommon CF mutations, which can provide crucial information about the prognosis of the disease and the relationships between genotype and phenotype. To ensure the success of creating novel, safer, and more efficient treatment approaches, a deeper understanding of the pathogeny of the illness is required. In the age of customized medicine, genetic research will be essential to improving patient care and quality of life for those with uncommon mutations.

An Innovative Non-Invasive Method for Early Detection and Monitoring of Acute Compartment Syndrome.

Background: Acute compartment syndrome is a major surgical emergency with complex pathophysiology and a highly unpredictable pattern of evolution. We hypothesized that the onset of acute compartment syndrome of the leg or forearm is associated with variations in the surface temperature of the distal segment (foot or hand) with a distinct pattern, which acts as an early warning sign. Materials and Methods: We developed a monitoring device that consists of two thermic sensors attached to a modular limb splint, which continuously measure the temperature difference between the proximal and distal regions of the limb (i.e., arm-hand, thigh-foot). Firstly, we investigated both the arm-hand and thigh-foot temperature gradients of hospitalized patients' healthy limbs (43 patients, 56 upper limbs, 64 lower limbs) in order to establish a baseline. Secondly, we examined the correlation between the thermic gradients and intracompartmental pressure values in compartment syndrome limbs (20 patients, 6 upper limbs, 14 lower limbs). Results: For the control group, the mean values for the normal limb thermic gradients were -0.17 °C for the upper limbs. and 0.03 °C for the lower limbs. In the impending compartment syndrome group (defined by intracompartmental pressure values), the mean index was -0.38 °C. In the fully developed compartment syndrome group, the mean value was 4.11 °C. Discussions: Analysis was performed using the ANOVA one-way statistical method. This showed significant differences between the compartment syndrome group and the impending and control groups. A decreasing trend in the thermic gradient in patients with impending compartment syndrome compared with the control group was noted. Conclusions: The thermic gradient of limbs presenting signs of impending compartment syndrome decreases as a result of the increased temperature of the distal segment. This pattern can be used as an early diagnostic method for acute compartment syndrome. This technique is non-invasive and bears no risk to the patient, allowing facile continuous monitoring during immobilization.

Unraveling chronic kidney disease in children: a surprising manifestation of celiac disease.

Celiac disease, firstly described in children, is a type of T-cell enteropathy that occurs in individuals genetically predisposed to gluten exposure. The estimated global prevalence of celiac disease is continuously increasing. Although, traditionally, celiac disease was diagnosed in children with failure to thrive and digestive issues, it is now recognized that may present with a wide range of symptoms beyond gastrointestinal ones. Celiac disease continues to pose significant challenges due to the continuous advancement of knowledge in understanding its pathophysiology, diagnosing the condition, managing its effects, and exploring potential therapeutic approaches. The prevalence of celiac disease is increased among individuals with chronic kidney disease, also. The most frequent associations are with diabetic nephropathy, IgA nephropathy and urolithiasis. A gut-kidney axis has been recognized to play a significant role in chronic kidney diseases. This literature review aims to review the chronic renal pathology associated with celiac disease, with emphasis on childhood.

Insights into the Management of Chronic Hepatitis in Children-From Oxidative Stress to Antioxidant Therapy.

Recent research has generated awareness of the existence of various pathophysiological pathways that contribute to the development of chronic diseases; thus, pro-oxidative factors have been accepted as significant contributors to the emergence of a wide range of diseases, from inflammatory to malignant. Redox homeostasis is especially crucial in liver pathology, as disturbances at this level have been linked to a variety of chronic diseases. Hepatitis is an umbrella term used to describe liver inflammation, which is the foundation of this disease regardless of its cause. Chronic hepatitis produces both oxidative stress generated by hepatocyte inflammation and viral inoculation. The majority of hepatitis in children is caused by a virus, and current studies reveal that 60-80% of cases become chronic, with many young patients still at risk of advancing liver damage. This review intends to emphasize the relevance of understanding these pathological redox pathways, as well as the need to update therapeutic strategies in chronic liver pathology, considering the beneficial effects of antioxidants.

Morphological Aspects of the Aberrant Right Subclavian Artery-A Systematic Review of the Literature.

BACKGROUND: The aberrant origin of the right subclavian artery (ARSA), also known as the lusoria artery, is a congenital malformation with an incidence of 0.5-4.4%. Most cases are incidental due to minimal clinical manifestations. Computer tomography (CT) is important in diagnosing and evaluating these patients. MATERIALS AND METHODS: We conduct a computerized search in two databases, PubMed and EMBASE, for articles published between 1 January 2022 and 31 December 2023, PROSPERO code: CRD42024511791. Eligible for inclusion were case reports and case series that presented the aberrant origin of the right subclavian artery. The main outcome was the highlighting of the morphological types of ARSA. In this context, we proposed a new classification system of this anomaly. The secondary outcome was the evaluation of the demographic distribution of the lusoria artery. RESULTS: Our search identified 47 articles describing 51 patients with ARSA. The typical course for ARSA is retroesophageal, being registered in 49 out of 51 patients. This malformation is frequently associated with Kommerell diverticulum (15 out of 51), troncus bicaroticus (7 out of 51), and aberrant origins of the right vertebral artery (7 out of 51). We observed a higher incidence of the condition among women (32 out of 51) compared to men (19 out of 51). From a demographic point of view, ARSA is more frequent in the "44 to 57 years" and "58 to 71 years" age ranges. CONCLUSIONS: ARSA is a congenital malformation resulting from a defect in the development of the aortic arches. The imaging studies such as computer tomography play a defined diagnostic role.

SARS-CoV-2 Seroprevalence in Children under 5 Years Old-A Regional Seroepidemiological Study.

Background and Objectives: The aim of this research was to assess the spread of SARS-CoV-2 infection; the study was motivated by parental hesitancy regarding child vaccination, and the potential passive immunity of infants acquired through breastfeeding from mothers vaccinated against COVID-19 or infected with SARS-CoV-2. Materials and Methods: We quantified the anti-SARS-CoV-2 immunoglobulin G (IgG) titer in the serum of 743 children under 5 years old, hospitalized between 1 August 2022, and 15 September 2023. Results: Among the participants, 52.76% had an anti-SARS-CoV-2 IgG titer that exceeded the reactivity threshold of the kit used, with an average of 1558.01 U/mL across the entire group. By age-specific categories, SARS-CoV-2 antibody prevalence was 43.04% for 0-12 months, 42.22% for 12-24 months, 61.67% for 24-36 months, 65.17% for 36-48 months, and 68.55% for 48-59 months. Gender analysis revealed 55.32% male participants, with a 52.07% seropositivity rate. Notably, IgG titer correlated positively with the child's age. Gender, admission diagnosis, and emergency department presentation were not variation factors of the IgG titer. Conclusions: The majority of children in the study group demonstrated IgG against SARS-CoV-2, and this rate increased with the child's age. Also, the IgG titer increased with the child's age.

Exploring the Microbial Landscape: Gut Dysbiosis and Therapeutic Strategies in Pancreatitis-A Narrative Review.

The gut microbiota is emerging as an important contributor to the homeostasis of the human body through its involvement in nutrition and metabolism, protection against pathogens, and the development and modulation of the immune system. It has therefore become an important research topic in recent decades. Although the association between intestinal dysbiosis and numerous digestive pathologies has been thoroughly researched, its involvement in pancreatic diseases constitutes a novelty in the specialized literature. In recent years, growing evidence has pointed to the critical involvement of the pancreas in regulating the intestinal microbiota, as well as the impact of the intestinal microbiota on pancreatic physiology, which implies the existence of a bidirectional connection known as the "gut-pancreas axis". It is theorized that any change at either of these levels triggers a response in the other component, hence leading to the evolution of pancreatitis. However, there are not enough data to determine whether gut dysbiosis is an underlying cause or a result of pancreatitis; therefore, more research is needed in this area. The purpose of this narrative review is to highlight the role of gut dysbiosis in the pathogenesis of acute and chronic pancreatitis, its evolution, and the prospect of employing the microbiota as a therapeutic intervention for pancreatitis.

Cardiac and Renal Fibrosis, the Silent Killer in the Cardiovascular Continuum: An Up-to-Date.

Cardiovascular disease (CVD) and chronic kidney disease (CKD) often coexist and have a major impact on patient prognosis. Organ fibrosis plays a significant role in the pathogenesis of cardio-renal syndrome (CRS), explaining the high incidence of heart failure and sudden cardiac death in these patients. Various mediators and mechanisms have been proposed as contributors to the alteration of fibroblasts and collagen turnover, varying from hemodynamic changes to the activation of the renin-angiotensin system, involvement of FGF 23, and Klotho protein or collagen deposition. A better understanding of all the mechanisms involved has prompted the search for alternative therapeutic targets, such as novel inhibitors of the renin-angiotensin-aldosterone system (RAAS), serelaxin, and neutralizing interleukin-11 (IL-11) antibodies. This review focuses on the molecular mechanisms of cardiac and renal fibrosis in the CKD and heart failure (HF) population and highlights the therapeutic alternatives designed to target the responsible pathways.