Management of Keloid-Associated Pruritus With Topical Crisaborole 2% Ointment: A Case Report.

Introduction: The pathophysiology of keloid formation is poorly understood, and current treatments, including intralesional corticosteroids, cryotherapy, and surgery, are often associated with high resistance to treatment and recurrence. The multifactorial pathogenesis of keloid formation suggests that aberrant inflammatory cytokine signaling associated with keratinocyte dysregulation may contribute to keloid-associated pruritus. Case Presentation: In this paper, we report 2 cases of keloid-associated pruritus that were successfully treated with topical crisaborole 2% ointment, a phosphodiesterase 4 (PDE4) inhibitor. Both patients had previously undergone multiple unsuccessful treatments before being treated with crisaborole 2% ointment. In both cases, the patients experienced complete relief of pruritus with no significant change in keloid size, thickness, or appearance. Conclusion: We propose that PDE4 inhibitors, such as crisaborole, may be an effective therapy for keloid- associated pruritus.

Epidemiological, clinical, biological and evolutionary profile of scorpion envenomed children under one year to 15 years in the Souss Massa region of Morocco.

Morocco is one of the main countries affected in North African with the scorpion envenomations. Faced with the threat, significant morbidity and a major risk of death especially in children, a detailed identification of scorpionic profile of stings remains important for health authorities at national or even regional level. The current study aims to establish the epidemiological, clinical, biological and evolutionary data of the scorpionism by analyzing 383 cases of scorpion stings in children from three age groups (<1 year, 1-5 years and >5 years), admitted at the Regional Hospital Hassan II-Agadir in the Souss Massa region during the period of 9 years and 10 months from January 2013 to October 2022. Our results showed that patients under 1 year of age presented the most severe cases and had the highest mortality rate. However, the clinical signs and symptoms observed illustrated severe damages to vital systems, particularly the cardiovascular, neurological and pulmonary systems, although the signs associated with the latter were present only in cases admitted in grades 2 and 3 for the three age categories studied. Fluctuations in vital constants (temperature and peripheral oxygen saturation, blood pressure, heart rate and respiratory rate), biochemical parameters (ASAT, ALAT, urea and blood creatine, as well as blood sugar) and CBC results revealed major functional disturbances in vital organs, especially in envenomated cases admitted in grade 3. A positive correlation was mentioned between the state of evolution and the various epidemiological parameters, digestive symptoms, as well as signs and symptoms linked to hemodynamic state, general and neurological state. The main interest is to illustrate the seriousness of scorpion envenomations, especially in the high-risk population, for whom an improved therapeutic approach in health centers will undoubtedly be reinforced, and the admission of immunotherapy, as a fundamental part of the treatment, remains important.

Understanding epileptogenesis from molecules to network alteration.

Epilepsy is characterized by recurrent seizures. Following an initial insult, a latent period precedes the onset of spontaneous seizures, a process referred to as epileptogenesis. This period plays a critical role in halting the progression toward epilepsy before the onset of abnormal molecular and network alterations. In this study, the fundamental concepts of epileptogenesis as well as the associated molecular and cellular targets are reviewed.

Hypertriglyceridemia: Molecular and Genetic Landscapes.

Lipid disorders represent one of the most worrisome cardiovascular risk factors. The focus on the impact of lipids on cardiac and vascular health usually concerns low-density lipoprotein cholesterol, while the role of triglycerides (TGs) is given poor attention. The literature provides data on the impact of higher plasma concentrations in TGs on the cardiovascular system and, therefore, on the outcomes and comorbidities of patients. The risk for coronary heart diseases varies from 57 to 76% in patients with hypertriglyceridemia. Specifically, the higher the plasma concentrations in TGs, the higher the incidence and prevalence of death, myocardial infarction, and stroke. Nevertheless, the metabolism of TGs and the exact physiopathologic mechanisms which try to explain the relationship between TGs and cardiovascular outcomes are not completely understood. The aims of this narrative review were as follows: to provide a comprehensive evaluation of the metabolism of triglycerides and a possible suggestion for understanding the targets for counteracting hypertriglyceridemia; to describe the inner physiopathological background for the relationship between vascular and cardiac damages derived from higher plasma concentrations in TGs; and to outline the need for promoting further insights in therapies for reducing TGs plasma levels.

A rapid protocol for inducing acute pancreatitis in zebrafish models.

Acute pancreatitis (AP) is an inflammatory disorder that occurs in the exocrine pancreas associated with tissue injury and necrosis. Experimental models of AP typically involve rodents, such as rats or mice. However, rodents exhibit divergent pathophysiological responses after the establishment of AP between themselves and in comparison, with human. The experiments conducted for this manuscript aimed to standardize a new AP model in zebrafish and validate it. Here, we provide a protocol for inducing AP in zebrafish through intraperitoneal injections of synthetic caerulein. Details are provided for solution preparation, pre-injection procedures, injection technique, and monitoring animal survival. Subsequently, validation was performed through biochemical and histological analyses of pancreatic tissue. The administered dose of caerulein for AP induction was 10 µg/kg applied four times in the intraperitoneal region. The histological validation study demonstrated the presence of necrosis within the first 12 h post-injection, accompanied by an excess of zymogen granules in the extracellular milieu. These observations align with those reported in conventional rodent models. We have standardized and validated the AP model in zebrafish. This model can contribute to preclinical and clinical studies of new drugs for AP treatment. Therefore, this novel model expands the toolkit for exploring faster and more effective preventive and therapeutic strategies for AP.

Traumatic lumbar spondylolisthesis: A case report and review of literature.

Traumatic spondylolisthesis of the lumbosacral junction (SPL) is a spinal injury rarely seen in current practice. Few cases are reported in the literature. It arises from complex trauma of high-energy mechanisms. We discussed the case of a young patient. He is 24 years old without notable pathological history victim of a traffic road accident. Clinically, he has no sensory or motor deficit, it is a spinal trauma classified American spinal injury association E (ASIA E) with severe back pain. A whole-body CT scan performed on admission showed a grade 2 L5-S1 SPL. A lumbar MRI revealed a tear of the disc at L5-S1. We performed a laminectomy to decompress the dural sheath and cauda equina roots with transforaminal lumbar interbody fusion. A postoperative CT scan showed the reduction of the spondylolisthesis. Two months later, the patient resumed walking. Surgery is the gold standard for the management of traumatic SPL. The aim of surgery is to achieve neural structure decompression and obtain stability with fusion.

Ventricular Intramyocardial Navigation for Tachycardia Ablation Guided by Electrograms (VINTAGE): Deep Ablation in Inaccessible Targets.

BACKGROUND: Deep intramural ventricular tachycardia substrate targets are difficult to access, map, and ablate from endocardial and epicardial surfaces, resulting in high recurrence rates. OBJECTIVES: In this study, the authors introduce a novel approach called ventricular intramyocardial navigation for tachycardia ablation guided by electrograms (VINTAGE) to access and ablate anatomically challenging ventricular tachycardia from within the myocardium. METHODS: Guidewire/microcatheter combinations were navigated deep throughout the extravascular myocardium, accessed directly from the right ventricle cavity, in Yorkshire swine (6 naive, 1 infarcted). Devices were steered to various intramyocardial targets including the left ventricle summit, guided by fluoroscopy, unipolar electrograms, and/or electroanatomic mapping. Radiofrequency ablations were performed to characterize ablation parameters and reproducibility. Intramyocardial saline irrigation began 1 minute before ablation and continued throughout. Lesions were analyzed on cardiac magnetic resonance and necropsy. RESULTS: VINTAGE was feasible in all animals within naive and infarcted myocardium. Forty-three lesions were created, using various guidewires and power settings. Forty-one (95%) lesions were detected on cardiac magnetic resonance and 38 (88%) on necropsy; all undetected lesions resulted from intentionally subtherapeutic ablation energy (10 W). Larger-diameter guidewires yielded larger size lesions. Lesion volumes on necropsy were significantly larger at 20 W than 10 W (178 mm3 [Q1-Q3: 104-382 mm3] vs 49 mm3 [Q1-Q3: 35-93 mm3]; P = 0.02). Higher power (30 W) did not create larger lesions. Median impedance dropped with preablation irrigation by 12 Ω (Q1-Q3: 8-17 Ω), followed by a further 15-Ω (Q1-Q3: 11-19 Ω) drop during ablation. Intramyocardial navigation, ablation, and irrigation were not associated with any complications. CONCLUSIONS: VINTAGE was safe and effective at creating intramural ablation lesions in targets traditionally considered inaccessible from the endocardium and epicardium, both naive and infarcted. Intramyocardial guidewire irrigation and ablation at 20 W creates reproducibly large intramural lesions.

[Take-home messages from the 2nd COPD 2023 Biennial of the French Society of Respiratory Diseases. Placing the patient at the center of the care pathway]. / Principaux messages de la deuxième Biennale BPCO 2023 de la SPLF. Le patient au cœur du parcours de soins.

INTRODUCTION: The second COPD Biennial organized by the COPD working group of the French Society of Respiratory Diseases took place in Paris (Cochin) on 13th December 2023. STATE OF THE ART: Major trends in 2023 were discussed; they encompassed concepts, definitions, biologics, care pathways, pulmonary rehabilitation and complex situations entailed by respiratory infections, cardiovascular comorbidities and pulmonary hypertension, and modalities of oxygen therapy and ventilation. PERSPECTIVES: The different talks underlined major changes in COPD including the concepts of pre-COPD, etiotypes, health trajectories and new definitions of exacerbation. Recent results in biologics for COPD open the door to new pharmacological options. Assessment of current care pathways in France highlighted some causes for concern. For example, pulmonary rehabilitation is a key but insufficiently practiced element. Respiratory infections require careful assessment and treatments. Diagnosis and treatment of cardiovascular comorbidities and pulmonary hypertension are of paramount importance. As of late, oxygen therapy and ventilation modalities have evolved, and are beginning to afford more personalized options. CONCLUSIONS: As regards COPD, a personalized approach is crucial, placing the patient at the center of the care pathway and facilitating coordination between healthcare providers.

Integrative Approaches for the Diagnosis and Management of Erosive Oral Lichen Planus.

Erosive oral lichen planus (EOLP) represents a significant challenge in dental and medical management due to its chronic inflammatory nature, painful symptoms, and impact on quality of life. This study aims to evaluate the current diagnostic approach with novel non-invasive techniques, such as dermoscopy, and also the landscape of treatment options for EOLP, focusing on its efficacy, safety, and the challenges that it present in clinical practice. Through a comprehensive literature review, we explored the use of topical corticosteroids, systemic immunosuppressants, biologics, and Janus kinase (JAK) inhibitors in treating EOLP, alongside examining patient compliance, psychological impacts, and the risk of adverse effects and recurrence. Our findings reveal that while topical corticosteroids are the cornerstone of EOLP treatment, offering symptomatic relief, their long-term use is limited by side effects and tolerance development. Systemic therapies and biologics provide alternatives for refractory cases but necessitate careful adverse effect monitoring. JAK inhibitors show promise as an innovative treatment avenue but require more evidence on long-term safety and efficacy. This study highlights the necessity of personalized treatment approaches due to the variable disease course and response to treatment, underscoring the importance of a multidisciplinary strategy in managing EOLP. The complexity of EOLP treatment, compounded by its psychological and quality of life impacts, demands ongoing research into targeted therapies, the establishment of standardized treatment protocols, and the development of effective outcome measures to improve patient care and treatment outcomes.

Headache Associated with Coronavirus Disease 2019.

Headache affects around half of patients in the acute phase of COVID-19 and generally occurs at the beginning of the symptomatic phase, has an insidious onset, and is bilateral, and of moderate to severe intensity. COVID-19 may also present complications that cause acute and persistent headaches, such as cerebrovascular diseases, rhinosinusitis, meningitis, and intracranial hypertension. In 10% to 20% of patients with COVID-19, headache may persist beyond the acute phase. In general, the headache improves over time. To date, there are no clinical trials that have assessed the treatment of persistent post-COVID-19 headache.

[Bile Acid Diarrhea].

Diarrhea is a very common gastrointestinal symptom, and the presence of higher concentrations of bile acid in the colon leads to bile acid diarrhea (BAD). In BAD patients, a portion of bile from the small intestine that is normally controlled by enterohepatic circulation is present at a high concentration in the lumen of the large intestine, resulting in increased motility and secretion of the large intestine. The prevalence of BAD is estimated to be 1-2% of the general population, and it comprises one-third of the instances of diarrhea-predominant irritable bowel syndrome. The clinical symptoms of BAD include chronic diarrhea, increased frequency of defecation, urgency to defecate, fecal incontinence, and cramping abdominal pain. The pathophysiology of BAD has not yet been fully elucidated. However, recent studies have reported increased intestinal permeability, shortened intestinal transit time, and changes in the intestinal microbial community to be the possible causes of BAD. Although fecal and serum bile acid tests are widely used for diagnosis, new test methods that are non-invasive, inexpensive, and have high sensitivity and specificity are needed at various institutions to facilitate the diagnosis. The selenium homo-tauro-cholic acid (SeHCAT) test is the gold standard for BAD diagnosis and severity assessment. The validation of several other serum markers, such as 7-hydroxy-4-cholesten-3-one (serum 7αC4) and the fibroblast growth factor 19 (FGF19) for use in clinical practice is ongoing. Although bile acid sequestrants are the mainstay of treatment, the development of drugs that are more effective and have better compliance is required. Farnesoid X receptor (FXR) agonists are showing promising results.

The Relevance, Predictability, and Utility of Annexin A5 for Human Physiopathology.

As an important functional protein molecule in the human body, human annexin A5 (hAnxA5) is widely found in human cells and body fluids. hAnxA5, the smallest type of annexin, performs a variety of biological functions by reversibly and specifically binding phosphatidylserine (PS) in a calcium-dependent manner and plays an important role in many human physiological and pathological processes. The free state hAnxA5 exists in the form of monomers and usually forms a polymer in a specific self-assembly manner when exerting biological activity. This review systematically discusses the current knowledge and understanding of hAnxA5 from three perspectives: physiopathological relevance, diagnostic value, and therapeutic utility. hAnxA5 affects the occurrence and development of many physiopathological processes. Moreover, hAnxA5 can be used independently or in combination as a biomarker of physiopathological phenomena for the diagnosis of certain diseases. Importantly, based on the properties of hAnxA5, many novel drug candidates have been designed and prepared for application in actual medical practice. However, there are also some gaps and shortcomings in hAnxA5 research. This in-depth study will not only expand the understanding of structural and functional relationships but also promote the application of hAnxA5 in the field of biomedicine.

Pathophysiology-Based Management of Secondary Injuries and Insults in TBI.

Traumatic Brain Injury (TBI) remains a leading cause of morbidity and mortality among all ages; despite the advances, understanding pathophysiological responses after TBI is still complex, involving multiple mechanisms. Previous reviews have focused on potential targets; however, the research on potential targets has continuously grown in the last five years, bringing even more alternatives and elucidating previous mechanisms. Knowing the key and updated pathophysiology concepts is vital for adequate management and better outcomes. This article reviews the underlying molecular mechanisms, the latest updates, and future directions for pathophysiology-based TBI management.

Sex Disparities in Rectal Cancer Surgery: An In-Depth Analysis of Surgical Approaches and Outcomes.

Anatomical and physiological differences exist between sex, leading to variations in how diseases, such as rectal cancer, are prevalence and treatment outcomes of diseases including rectal cancer. In particular, in the case of rectal cancer, anatomical differences may be associated with surgical challenges, and these factors are believed to be important contributors to potential disparities in postoperative recovery, associated complications, and oncological outcomes between male and female patients. However, there is still ongoing debate regarding this matter. Significantly, the male pelvic anatomy is distinguished by its narrower dimensions, which can present surgical challenges and impede visual access during operative procedures, rendering it more complex than surgical interventions in the female pelvis. As a result, this anatomical difference leads to a greater occurrence of postoperative complications, such as anastomotic leakage. Moreover, the pelvis houses nerves that are vital for urinary and genital functions, underscoring the need to assess the potential risks of sexual and urinary dysfunction in rectal cancer surgery. These postoperative complications can significantly impact the quality of life; therefore, it is imperative to perform surgery with an understanding of the structural differences between sexes. Therefore, to address the limitations imposed by anatomical structures, new approaches such as robotic surgery, trans-anal total mesorectal excision, and intraoperative neuromonitoring are being introduced. Furthermore, it is essential to conduct research into fundamental mechanisms that may give rise to differences in surgical outcomes and oncological results between sexes. By comprehending the disparities between males and females, we can advance toward personalized treatments. Consequently, this review outlines variations in surgical approaches, complications, and treatments for rectal cancer in male and female patients.

Diagnosis and management of Achilles tendon ailments: the Scottish mist.

The diagnosis and management of Achilles tendon ailments continue to be widely discussed by the scientific community. Also, the nomenclature used to describe the tendinopathic lesion in patients changed over the last decades together with the evolution in the knowledge of the physiopathology of Achilles tendinopathy, and unfortunately, through ignorance and possibly laziness, confusion still abounds. To emerge from these foggy paths, some clarifications are still necessary. The present Editorial tries to clarify some of these issues.

The Impact of Inotropes and Vasopressors on Cerebral Oxygenation in Patients with Traumatic Brain Injury and Subarachnoid Hemorrhage: A Narrative Review.

Traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) are critical neurological conditions that necessitate specialized care in the Intensive Care Unit (ICU). Managing cerebral perfusion pressure (CPP) and mean arterial pressure (MAP) is of primary importance in these patients. To maintain targeted MAP and CPP, vasopressors and/or inotropes are commonly used. However, their effects on cerebral oxygenation are not fully understood. The aim of this review is to provide an up-to date review regarding the current uses and pathophysiological issues related to the use of vasopressors and inotropes in TBI and SAH patients. According to our findings, despite achieving similar hemodynamic parameters and CPP, the effects of various vasopressors and inotropes on cerebral oxygenation, local CBF and metabolism are heterogeneous. Therefore, a more accurate understanding of the cerebral activity of these medications is crucial for optimizing patient management in the ICU setting.

Peripheral Microvascular Dysfunction in Children and Adults with Congenital Heart Disease: A Literature Review.

Although there is a continually growing number of patients with congenital heart disease (CHD) due to medical and surgical advances, these patients still have a poorer prognosis compared to healthy individuals of similar age. In patients with heart failure, microvascular dysfunction (MVD) has recently emerged as a crucial modulator of disease initiation and progression. Because of the substantial pathophysiological overlap between CHD and heart failure induced by other etiologies, MVD could be important in the pathophysiology of CHD as well. MVD is believed to be a systemic disease and may be manifested in several vascular beds. This review will focus on what is currently known about MVD in the peripheral vasculature in CHD. Therefore, a search on the direct assessment of the vasodilatory capacity of the peripheral microcirculation in patients with CHD was conducted in the PubMed database. Since there is little data available and the reported studies are also very heterogeneous, peripheral MVD in CHD is not sufficiently understood to date. Its exact extent and pathophysiological relevance remain to be elucidated in further research.

Osteoarthritis versus psoriasis arthritis: Physiopathology, cellular signaling, and therapeutic strategies.

Osteoarthritis and psoriasis arthritis are two degenerative forms of arthritis that share similar yet also different manifestations at the histological, cellular, and clinical levels. Rheumatologists have marked them as two entirely distinct arthropathies. Given recent discoveries in disease initiation and progression, potential mechanisms, cellular signaling pathways, and ongoing clinical therapeutics, there are now more opportunities for discovering osteoarthritis drugs. This review summarized the osteoarthritis and psoriasis arthritis signaling pathways, crosstalk between BMP, WNT, TGF-ß, VEGF, TLR, and FGF signaling pathways, biomarkers, and anatomical pathologies. Through bench research, we demonstrated that regenerative medicine is a promising alternative for treating osteoarthritis by highlighting significant scientific discoveries on entheses, multiple signaling blockers, and novel molecules such as immunoglobulin new antigen receptors targeted for potential drug evaluation. Furthermore, we offered valuable therapeutic approaches with a multidisciplinary strategy to treat patients with osteoarthritis or psoriasis arthritis in the coming future in the clinic.

Controversial Past, Splendid Present, Unpredictable Future: A Brief Review of Alzheimer Disease History.

Background: The concept of Alzheimer disease (AD)-since its histological discovery by Alzheimer to the present day-has undergone substantial modifications. Methods: We conducted a classical narrative review of this field with a bibliography selection (giving preference to Medline best match). Results: The following subjects are reviewed and discussed: Alzheimer's discovery, Kraepelin's creation of a new disease that was a rare condition until the 1970's, the growing interest and investment in AD as a major killer in a society with a large elderly population in the second half of the 20th century, the consolidation of the AD clinicopathological model, and the modern AD nosology based on the dominant amyloid hypothesis among many others. In the 21st century, the development of AD biomarkers has supported a novel biological definition of AD, although the proposed therapies have failed to cure this disease. The incidence of dementia/AD has shown a decrease in affluent countries (possibly due to control of risk factors), and mixed dementia has been established as the most frequent etiology in the oldest old. Conclusions: The current concept of AD lacks unanimity. Many hypotheses attempt to explain its complex physiopathology entwined with aging, and the dominant amyloid cascade has yielded poor therapeutic results. The reduction in the incidence of dementia/AD appears promising but it should be confirmed in the future. A reevaluation of the AD concept is also necessary.