A Potential Role of Interleukin-5 in the Pathogenesis and Progression of Amyotrophic Lateral Sclerosis: A New Molecular Perspective.

Cumulative data suggest that neuroinflammation plays a prominent role in amyotrophic lateral sclerosis (ALS) pathogenesis. The purpose of this work was to assess if patients with ALS present a specific peripheral cytokine profile and if it correlates with neurological disability assessed by ALSFRS-R, the rate of disease progression, and the pattern of disease progression (horizontal spreading [HSP] versus vertical spreading [VSP]). We determined the levels of 15 cytokines in the blood of 59 patients with ALS and 40 controls. We identified a positive correlation between levels of pro-inflammatory cytokines (interleukin [IL]-17F, IL-33, IL-31) and the age of ALS patients, as well as a positive correlation between IL-12p/70 and survival from ALS onset and ALS diagnosis. Additionally, there was a positive correlation between the ALSFRS-R score in the upper limb and respiratory domain and IL-5 levels. In our ALS cohort, the spreading pattern was 42% horizontal and 58% vertical, with patients with VSP showing a faster rate of ALS progression. Furthermore, we identified a negative correlation between IL-5 levels and the rate of disease progression, as well as a positive correlation between IL-5 and HSP of ALS. To the best of our knowledge, this is the first study reporting a "protective" role of IL-5 in ALS.

Pathophysiology, Histopathology, and Differential Diagnostics of Basal Cell Carcinoma and Cutaneous Squamous Cell Carcinoma-An Update from the Pathologist's Point of View.

Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) are the most frequently occurring non-melanocytic skin cancers. The objective of our study is to present the pathophysiology of BCC and cSCC and its direct relationship with the histopathological diagnostics and the differential diagnostics of these types of cancer, based on the morphological characteristics, immunohistochemical profile, and genetic alterations. The qualitative study was based on emphasizing the morphological characteristics and immunohistochemistry profiles of BCC and cSCC and the differential diagnostics based on the tissue samples from the Clinical Pathology Department of Mures Clinical County Hospital between 2020 and 2022. We analyzed the histopathological appearances and immunohistochemical profiles of BCC and cSCC in comparison with those of Bowen disease, keratoacanthoma, hyperkeratotic squamous papilloma, metatypical carcinoma, pilomatricoma, trichoblastoma, Merkel cell carcinoma, pleomorphic dermal sarcoma (PDS), and melanoma. Our study showed the importance of the correct histopathological diagnosis, which has a direct impact on the appropriate treatment and outcome for each patient. The study highlighted the histopathological and morphological characteristics of NMSCs and the precursor lesions in HE and the immunohistochemical profile for lesions that may make the differential diagnosis difficult to establish.

Long-Term Disability Outcomes in Relapsing-Remitting Multiple Sclerosis Patients: Impact of Clinical and Demographic Factors on Disease Progression.

Background: Multiple sclerosis (MS) is a prevalent chronic inflammatory and neurodegenerative disease of the central nervous system. The main evolving forms, relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS), lack clear delineation. Methods: We conducted an observational study on 523 Caucasian RRMS patients receiving first-line disease-modifying therapies (DMTs), analyzing demographic, clinical, and geographical data. Results: RRMS patients experienced a statistically significant reduction in relapse rates post-DMT initiation. Significant differences in time to reach an Expanded Disability Status Score (EDSS) of 3.0 and 6.0 were observed based on demographics and onset topography. Kaplan-Meier analysis revealed that the onset with optic or supratentorial symptoms is linked to a longer time until EDSS = 3.0 is reached. Urban origin correlated with a prolonged time until EDSS = 3.0. Gender and environment showed no significant associations with the hazard of reaching an EDSS = 6.0. Cox regression analysis revealed no significant impact of relapses on the time to reach EDSS scores of 3.0 and 6.0 in our study cohort. Conclusions: Multivariate analysis identified several predictive factors for disability progression, including environment, age at onset, and disability level at DMT initiation.

Incidental Finding of Persistent Trigeminal Artery in a Young Woman: A Case Report.

Persistent trigeminal artery disease is one of the most common types of persistent carotid-vertebrobasilar anastomoses. Usually, it is unilateral, and it can be discovered with a magnetic resonance angiography (MRA), computed tomography angiography (angioCT), or classic angiography exam. It can be associated with non-specific symptoms, such as headaches, or more specific ones, such as III or VI nerve palsy or trigeminal neuralgia, but most of the time it goes undetected, being an incidental finding and not causing any symptoms. On MRA and angioCT, it has the characteristic "tau" sign. We present the case of a young woman who, incidentally, discovered this malformation after undergoing an MRA. She had been experiencing a persistent headache without a known cause, which did not improve despite medication.

Characteristics of Developmental and Epileptic Encephalopathy Associated with PACS2 p.Glu209Lys Pathogenic Variant-Our Experience and Systematic Review of the Literature.

BACKGROUND: Developmental and epileptic encephalopathies (DEE) encompass a group of rare diseases with hereditary and genetic causes as well as acquired causes such as brain injuries or metabolic abnormalities. The phosphofurin acidic cluster sorting protein 2 (PACS2) is a multifunctional protein with nuclear gene expression. The first cases of the recurrent c.625G>A pathogenic variant of PACS2 gene were reported in 2018 by Olson et al. Since then, several case reports and case series have been published. METHODS: We performed a systematic review of the PUBMED and SCOPUS databases using Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Our search parameters included DEE66 with a pathogenic PACS2 gene p.Glu209Lys mutation published cases to which we added our own clinical experience regarding this pathology. RESULTS: A total of 11 articles and 29 patients were included in this review, to which we added our own experience for a total of 30 patients. There was not a significant difference between sexes regarding the incidence of this pathology (M/F: 16/14). The most common neurological and psychiatric symptoms presented by the patients were: early onset epileptic seizures, delayed global development (including motor and speech delays), behavioral disturbances, limited intellectual capacity, nystagmus, hypotonia, and a wide-based gait. Facial dysmorphism and other organs' involvement were also frequently reported. Brain MRIs evidenced anomalies of the posterior cerebellar fossa, foliar distortion of the cerebellum, vermis hypoplasia, white matter reduction, and lateral ventricles enlargement. Genetic testing is more frequent in children. Only 4 cases have been reported in adults to date. CONCLUSIONS: It is important to maintain a high suspicion of new pathogenic gene variants in adult patients presenting with a characteristic clinical picture correlated with radiologic changes. The neurologist must gradually recognize the distinct evolving phenotype of DEE66 in adult patients, and genetic testing must become a scenario with which the neurologist attending adult patients should be familiar. Accurate diagnosis is required for adequate treatment, genetic counseling, and an improved long-term prognosis.

COVID-19 and Clostridioides difficile Coinfection Analysis in the Intensive Care Unit.

Since the emergence of SARS-CoV-2 in late 2019, the global mortality attributable to COVID-19 has reached 6,972,152 deaths according to the World Health Organization (WHO). The association between coinfection with Clostridioides difficile (CDI) and SARS-CoV-2 has limited data in the literature. This retrospective study, conducted at Mureș County Clinical Hospital in Romania, involved 3002 ICU patients. Following stringent inclusion and exclusion criteria, 63 patients were enrolled, with a division into two subgroups-SARS-CoV-2 + CDI patients and CDI patients. Throughout their hospitalization, the patients were closely monitored. Analysis revealed no significant correlation between comorbidities and invasive mechanical ventilation (IMV) or non-invasive mechanical ventilation (NIMV). However, statistically significant associations were noted between renal and hepatic comorbidties (p = 0.009), death and CDI-SARS-CoV-2 coinfection (p = 0.09), flourochinolone treatment and CDI-SARS-CoV-2 infection (p = 0.03), and an association between diabetes mellitus and SARS-CoV-2-CDI infection (p = 0.04), as well as the need for invasive mechanical ventilation (p = 0.04). The patients with CDI treatment were significantly younger and received immuno-modulator or corticotherapy treatment, which was a risk factor for opportunistic agents. Antibiotic and PPI (proton pump inhibitor) treatment were significant risk factors for CDI coinfection, as well as for death, with PPI treatment in combination with antibiotic treatment being a more significant risk factor.

Elevated Leukocyte Glucose Index Is Associated with Long-Term Arteriovenous Fistula Failure in Dialysis Patients.

(1) Background: Arteriovenous fistula (AVF) is the preferred type of vascular access for dialysis in patients with end-stage kidney disease (ESKD). However, the primary patency of AVF at one year is under 70% due to several risk factors and comorbidities. Leukocyte glucose index (LGI), a new biomarker based on blood leukocytes and glucose values, has been found to be associated with poor outcomes in cardiovascular disease. The aim of this study is to analyze the impact of LGI on the long-term primary patency of AVF following dialysis initiation. (2) Methods: We conducted a retrospective observational study in which we initially enrolled 158 patients with ESKD admitted to the Vascular Surgery Department of the Emergency County Hospital of Targu Mures, Romania, to surgically create an AVF for dialysis between January 2020 and July 2023. The primary endpoint was AVF failure, defined as the impossibility of performing a chronic dialysis session due to severe restenosis or AVF thrombosis. After follow-up, we categorized patients into two groups based on their AVF status: "functional AVF" for those with a permeable AVF and "AVF failure" for those with vascular access dysfunction. (3) Results: Patients with AVF failure had a higher prevalence of atrial fibrillation (p = 0.013) and diabetes (p = 0.028), as well as a higher LGI value (1.12 vs. 0.79, p < 0.001). At ROC analysis, LGI had the strongest association with the outcome, with an AUC of 0.729, and an optimal cut-off value of 0.95 (72.4% sensitivity and 68% specificity). In Kaplan-Meier survival analyses, patients in the highest tertile (T3) of LGI had a significantly higher incidence of AVF failure compared to those in tertile 1 (p = 0.019). Moreover, we found that patients with higher baseline LGI values had a significantly higher risk of AVF failure during follow-up (HR: 1.48, p = 0.003). The association is independent of age and sex (HR: 1.65, p = 0.001), cardiovascular risk factors (HR: 1.63, p = 0.012), and pre-operative vascular mapping determinations (HR: 3.49, p = 0.037). (4) Conclusions: In conclusion, high preoperative values of LGI are positively associated with long-term AVF failure. The prognostic role of the biomarker was independent of age, sex, cardiovascular risk factors, and pre-operative vascular mapping determinations.