Excessive supraventricular ectopic activity and future onset of atrial fibrillation in patients with cryptogenic stroke.

OBJECTIVES: Although evidence has shown the association of excessive supraventricular ectopic activity (ESVEA) with future development of atrial fibrillation (AF), this relationship is not yet fully understood. This study examines whether ESVEA can predict the future onset of AF, in patients presenting with cryptogenic stroke. MATERIALS AND METHODS: A retrospective cohort of 124 non-AF, consecutive patients, hospitalized for cryptogenic stroke between 2014 and 2015, was retrieved. 24-h inpatient monitoring with Holter was employed to reveal ESVEA, defined as the presence of more than 20 premature atrial complexes per hour (PACs/h) on average, or a more than 5 s duration of the longest supraventricular run (LSVR). After a median follow-up period of 5.2 years, the patients were examined for AF. RESULTS: From initial 124 patients, 12 died and one was lost during follow-up. For the total of 111 patients finally included, the median age was 56 years and 25.2% were females. The overall baseline median CHA2DS2-VASc score was 3. AF was found in 13 (11.71%) patients. Patients who were finally diagnosed with AF had a significantly higher number of PACs/h and a longer median LSVR duration at baseline (16.67 vs. 0.21, p < 0.001 and 3 vs. 0 s, p < 0.001, respectively). The presence of ESVEA was also significantly more frequent among AF patients (46.15%, 95%CI: 17.78%-74.22%) compared to non-AF ones (6.1%, 95%CI: 1.3%-10.7%, p < 0.001). CONCLUSIONS: Excessive atrial ectopy, detected with 24 h inpatient Holter monitoring, is a significant indicator of future development of AF in patients presenting originally with a cryptogenic stroke.

Association between Helicobacter pylori infection and Guillain-Barré Syndrome: A meta-analysis.

BACKGROUND: Helicobacter pylori (H pylori) is a Gram-negative bacterium, considered to trigger autoimmune gastrointestinal disorders. This pathogen has also been linked to the autoimmune sequelae in extra-gastrointestinal diseases and peripheral neuropathies. Guillain-Barré syndrome (GBS) is a serious autoimmune demyelinating disorder of peripheral nerves, usually with a post-infectious onset. About 30% of cases of GBS attributed to by Campylobacter jejuni, so, H pylori, could be also involved. Growing evidence suggests the likely involvement of H pylori infection in the development of GBS. The aim of the current study was to therefore estimate the prevalence of H pylori antibodies in GBS. METHODS: A search of the literature was performed, using the PUBMED database, until December 2018. Data were extracted from six case-control studies, and a stratification analysis was conducted according to cerebrospinal fluid (CSF) or serum detection material. RESULTS: Among 29 records found, 6 studies met in the inclusion criteria for the meta-analysis. In the CSF subgroup, 105 participants were involved (40 GBS patients and 65 controls), while the serum subgroup included 325 participants (152 GBS and 173 controls). Data were combined using a fixed-effects model. Anti-H pylori IgG were significantly more prevalent in GBS patients compared to controls, in both CSF (95% CI: 9.66-186.56, OR: 42.45, Pz < .00001) and serum (95% CI: 1.30-4.11, OR: 2.31, Pz: .004) subgroups. CONCLUSION: The present meta-analysis showed a strong association between GBS and the presence of H pylori antibodies, especially in CSF, thereby suggesting a role of H pylori infection in the pathophysiology of GBS.

New molecular diagnostic trends and biomarkers for amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a rare and fatal neurodegenerative disorder. Two forms are recognized, familial (FALS) that accounts for 5-10% of ALS cases, and sporadic (SALS) that accounts for the rest. Early diagnosis of ALS is important because it improves their therapeutic efficacy. Current diagnosis is based on clinical assessment and requires approximately 12 months, leading to a significant delay in drug administration. Therefore, new methods are required for the earlier diagnosis of ALS. Screening for pathogenic variants in known ALS-associated genes is already exploited as a diagnostic tool in ALS but cannot be applied for population-based screening. New circulating biomarkers (proteins or small molecules) are needed for initial screening, whereas specific diagnostic methods can be applied to confirm the presence of pathogenic variants in the selected population subgroup. Lipids appear as promising biomarkers for population-based screening and for monitoring disease progression. Genetic analysis can also assist in the prediction of disease progression by analyzing disease-modifying genes, for example, EPHA4 and CHGB. Furthermore, molecular diagnosis will aid the stratification of ALS patients for improved pharmacological approaches. Here, we discuss current and novel diagnostic strategies and how they can be applied to revolutionize the field of ALS molecular diagnosis.

Acute Liver Failure: From Textbook to Emergency Room and Intensive Care Unit With Concomitant Established and Modern Novel Therapies.

Acute liver failure is a rare hepatic emergent situation that affects primarily young people and has often a catastrophic or even fatal outcome. Definition of acute liver failure has not reached a universal consensus and the interval between the appearance of jaundice and hepatic encephalopathy for the establishment of the acute failure is a matter of debate. Among the wide variety of causes, acetaminophen intoxication in western societies and viral hepatitis in the developing countries rank at the top of the etiology list. Identification of the clinical appearance and initial management for the stabilization of the patient are of vital significance. Further advanced therapies, that require intensive care unit, should be offered. The hallmark of treatment for selected patients can be orthotopic liver transplantation. Apart from well-established treatments, novel therapies like hepatocyte or stem cell transplantation, additional new therapeutic strategies targeting acetaminophen intoxication and/or hepatic encephalopathy are mainly experimental, and some of them do not belong, yet, to clinical practice. For clinicians, it is substantial to have the alertness to timely identify the patient and transfer them to a specialized center, where more treatment opportunities are available.

Genomic variants in the FTO gene are associated with sporadic amyotrophic lateral sclerosis in Greek patients.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating disease whose complex pathology has been associated with a strong genetic component in the context of both familial and sporadic disease. Herein, we adopted a next-generation sequencing approach to Greek patients suffering from sporadic ALS (together with their healthy counterparts) in order to explore further the genetic basis of sporadic ALS (sALS). RESULTS: Whole-genome sequencing analysis of Greek sALS patients revealed a positive association between FTO and TBC1D1 gene variants and sALS. Further, linkage disequilibrium analyses were suggestive of a specific disease-associated haplotype for FTO gene variants. Genotyping for these variants was performed in Greek, Sardinian, and Turkish sALS patients. A lack of association between FTO and TBC1D1 variants and sALS in patients of Sardinian and Turkish descent may suggest a founder effect in the Greek population. FTO was found to be highly expressed in motor neurons, while in silico analyses predicted an impact on FTO and TBC1D1 mRNA splicing for the genomic variants in question. CONCLUSIONS: To our knowledge, this is the first study to present a possible association between FTO gene variants and the genetic etiology of sALS. In addition, the next-generation sequencing-based genomics approach coupled with the two-step validation strategy described herein has the potential to be applied to other types of human complex genetic disorders in order to identify variants of clinical significance.

Review: Impact of Helicobacter pylori on Alzheimer's disease: What do we know so far?

BACKGROUND: Helicobacter pylori has changed radically gastroenterologic world, offering a new concept in patients' management. Over time, more medical data gave rise to diverse distant, extragastric manifestations and interactions of the "new" discovered bacterium. Special interest appeared within the field of neurodegenerative diseases and particularly Alzheimer's disease, as the latter and Helicobacter pylori infection are associated with a large public health burden and Alzheimer's disease ranks as the leading cause of disability. However, the relationship between Helicobacter pylori infection and Alzheimer's disease remains uncertain. METHODS: We performed a narrative review regarding a possible connection between Helicobacter pylori and Alzheimer's disease. All accessible relevant (pre)clinical studies written in English were included. Both affected pathologies were briefly analyzed, and relevant studies are discussed, trying to focus on the possible pathogenetic role of this bacterium in Alzheimer's disease. RESULTS: Data stemming from both epidemiologic studies and animal experiments seem to be rather encouraging, tending to confirm the hypothesis that Helicobacter pylori infection might influence the course of Alzheimer's disease pleiotropically. Possible main mechanisms may include the bacterium's access to the brain via the oral-nasal-olfactory pathway or by circulating monocytes (infected with Helicobacter pylori due to defective autophagy) through disrupted blood-brain barrier, thereby possibly triggering neurodegeneration. CONCLUSIONS: Current data suggest that Helicobacter pylori infection might influence the pathophysiology of Alzheimer's disease. However, further large-scale randomized controlled trials are mandatory to clarify a possible favorable effect of Helicobacter pylori eradication on Alzheimer's disease pathophysiology, before the recommendation of short-term and cost-effective therapeutic regimens against Helicobacter pylori-related Alzheimer's disease.

Multiple sclerosis deep grey matter: the relation between demyelination, neurodegeneration, inflammation and iron.

In multiple sclerosis (MS), diffuse degenerative processes in the deep grey matter have been associated with clinical disabilities. We performed a systematic study in MS deep grey matter with a focus on the incidence and topographical distribution of lesions in relation to white matter and cortex in a total sample of 75 MS autopsy patients and 12 controls. In addition, detailed analyses of inflammation, acute axonal injury, iron deposition and oxidative stress were performed. MS deep grey matter was affected by two different processes: the formation of focal demyelinating lesions and diffuse neurodegeneration. Deep grey matter demyelination was most prominent in the caudate nucleus and hypothalamus and could already be seen in early MS stages. Lesions developed on the background of inflammation. Deep grey matter inflammation was intermediate between low inflammatory cortical lesions and active white matter lesions. Demyelination and neurodegeneration were associated with oxidative injury. Iron was stored primarily within oligodendrocytes and myelin fibres and released upon demyelination. In addition to focal demyelinated plaques, the MS deep grey matter also showed diffuse and global neurodegeneration. This was reflected by a global reduction of neuronal density, the presence of acutely injured axons, and the accumulation of oxidised phospholipids and DNA in neurons, oligodendrocytes and axons. Neurodegeneration was associated with T cell infiltration, expression of inducible nitric oxide synthase in microglia and profound accumulation of iron. Thus, both focal lesions as well as diffuse neurodegeneration in the deep grey matter appeared to contribute to the neurological disabilities of MS patients.

Impact of Helicobacter pylori and metabolic syndrome on mast cell activation-related pathophysiology and neurodegeneration.

Both Helicobacter pylori (H. pylori) infection and metabolic syndrome (MetS) are highly prevalent worldwide. The emergence of relevant research suggesting a pathogenic linkage between H. pylori infection and MetS-related cardio-cerebrovascular diseases and neurodegenerative disorders, particularly through mechanisms involving brain pericyte deficiency, hyperhomocysteinemia, hyperfibrinogenemia, elevated lipoprotein-a, galectin-3 overexpression, atrial fibrillation, and gut dysbiosis, has raised stimulating questions regarding their pathophysiology and its translational implications for clinicians. An additional stimulating aspect refers to H. pylori and MetS-related activation of innate immune cells, mast cells (MC), which is an important, often early, event in systemic inflammatory pathologies and related brain disorders. Synoptically, MC degranulation may play a role in the pathogenesis of H. pylori and MetS-related obesity, adipokine effects, dyslipidemia, diabetes mellitus, insulin resistance, arterial hypertension, vascular dysfunction and arterial stiffness, an early indicator of atherosclerosis associated with cardio-cerebrovascular and neurodegenerative disorders. Meningeal MC can be activated by triggers including stress and toxins resulting in vascular changes and neurodegeneration. Likewise, H.pylori and MetS-related MC activation is linked with: (a) vasculitis and thromboembolic events that increase the risk of cardio-cerebrovascular and neurodegenerative disorders, and (b) gut dysbiosis-associated neurodegeneration, whereas modulation of gut microbiota and MC activation may promote neuroprotection. This narrative review investigates the intricate relationship between H. pylori infection, MetS, MC activation, and their collective impact on pathophysiological processes linked to neurodegeneration. Through a comprehensive search of current literature, we elucidate the mechanisms through which H. pylori and MetS contribute to MC activation, subsequently triggering cascades of inflammatory responses. This highlights the role of MC as key mediators in the pathogenesis of cardio-cerebrovascular and neurodegenerative disorders, emphasizing their involvement in neuroinflammation, vascular dysfunction and, ultimately, neuronal damage. Although further research is warranted, we provide a novel perspective on the pathophysiology and management of brain disorders by exploring potential therapeutic strategies targeting H. pylori eradication, MetS management, and modulation of MC to mitigate neurodegeneration risk while promoting neuroprotection.

Mental illness through the perspective of undergraduate medical students in Greece: a cross-sectional study at Aristotle University of Thessaloniki.

Introduction: Numerous studies reveal that mental health-related stigma, stereotypes, and prejudices negatively affect the patients, jeopardizing their health, prognosis, and social opportunities. Healthcare professionals, who are in the first line of combating mental disease, are expected to play a significant role in drastically changing discriminatory and stigmatizing attitudes toward psychiatric patients and in diminishing the existing healthcare and social disparities. In this study, we aimed to explore and highlight the views of Greek medical students-that is of the future physicians-toward mental illness and people suffering from it. Materials and methods: It is a cross-sectional, observational study, in which 324 undergraduate students from the most populous Greek medical school of the Aristotle University of Thessaloniki, participated online, during the spring semester of 2022. The tools used were the Opinions about Mental Illness Scale (OMI) that assesses one's viewpoints about mental illness, the Social Distance Scale (SDS) that captures the desired degree of social distancing from patients with mental disorders, and the Level of Contact Report (LCR-12) that estimates the level of familiarity with them. Results: Participants displayed rather positive attitudes regarding the etiology of mental illness, social integration, and discrimination toward psychiatric patients [as evaluated with the respective OMI subscales; Etiology mean score (µ):8.87 ± 4.68, Social Integration (µ):17.79 ± 5.42, Social Discrimination (µ):13.54 ± 11.17], and more clearly favorable opinions concerning the need for social provision or the enactment of restrictive measures [as expressed with the relative OMI subscales; Social Care (µ):22.74 ± 4.56, Social Restriction (µ):13.27 ± 8.98], while claiming to be quite familiar with mental disorders and individuals experiencing them (as assessed with LCR; µ: 8.71 ± 2.16), and relatively willing to interact with them (as measured with SDS; µ:8.95 ± 4.23). Degree of familiarity with mental illness was directly proportional to the desire for contact with patients living with it, while the higher both were, the more improved most of the aforementioned OMI sectors were found to be. Female sex, clinical medical education, previous clinical psychiatric training, and living with or being a person with a mental disorder were the factors that defined a statistically refined profile in many of the aspects above. Conclusion: Our findings are in accordance with many prior and recent studies, while showing improved opinions compared to those of previous research in Greek student and healthcare population. They are calling for vigilance, rather than complacency, as well as educational and social interventions, in order to enable current and future healthcare professionals to perform their function to its fullest extent. Implications of our results and further research suggestions are included.

The Pre-Interictal Network State in Idiopathic Generalized Epilepsies.

Generalized spike wave discharges (GSWDs) are the typical electroencephalographic findings of Idiopathic Generalized Epilepsies (IGEs). These discharges are either interictal or ictal and recent evidence suggests differences in their pathogenesis. The aim of this study is to investigate, through functional connectivity analysis, the pre-interictal network state in IGEs, which precedes the formation of the interictal GSWDs. A high-density electroencephalogram (HD-EEG) was recorded in twenty-one patients with IGEs, and cortical connectivity was analyzed based on lagged coherence and individual anatomy. Graph theory analysis was used to estimate network features, assessed using the characteristic path length and clustering coefficient. The functional connectivity analysis identified two distinct networks during the pre-interictal state. These networks exhibited reversed connectivity attributes, reflecting synchronized activity at 3-4 Hz (delta2), and desynchronized activity at 8-10.5 Hz (alpha1). The delta2 network exhibited a statistically significant (p < 0.001) decrease in characteristic path length and an increase in the mean clustering coefficient. In contrast, the alpha1 network showed opposite trends in these features. The nodes influencing this state were primarily localized in the default mode network (DMN), dorsal attention network (DAN), visual network (VIS), and thalami. In conclusion, the coupling of two networks defined the pre-interictal state in IGEs. This state might be considered as a favorable condition for the generation of interictal GSWDs.

Effect of spironolactone on pharmacological treatment of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) was recently renamed to metabolic (dysfunction)-associated fatty liver disease (MAFLD) to better characterize its pathogenic origin. NAFLD represents, at least in western societies, a potential epidemic with raising prevalence. Its multifactorial pathogenesis is partially unraveled and till now there is no approved pharmacotherapy for NAFLD. A plethora of various choices are investigated in clinical trials, targeting an arsenal of different pathways and molecules. Since the mineralocorticoid receptor (MR) and renin-angiotensin-aldosterone system (RAAS) appear to be implicated in NAFLD, within this concise review, we focus on a rather classical and inexpensive pharmacological agent, spironolactone. We present the current lines of evidence of MR and RAAS-related preclinical models and human trials reporting an association with NAFLD. In conclusion, evidence about spironolactone of RAAS is commented, as potential future pharmacological management of NAFLD.

Nonalcoholic fatty liver disease: multimodal treatment options for a pathogenetically multiple-hit disease.

Nonalcoholic fatty liver disease (NAFLD) has emerged as a significant public health problem. Besides the liver, NAFLD is also associated with increased cardiovascular and overall morbidity and mortality. NAFLD warrants intensive research, because no treatment has been established as yet. This may be partly attributed to the fact that the majority of the relative clinical trials have a monotherapeutic direction. However, the multifactorial pathogenesis of NAFLD may probably direct clinical trials to a combined therapeutic approach. The aim of this review is to provide a description of the multifactorial pathogenesis of NAFLD and type II diabetes mellitus-NAFLD interplay, and to summarize the therapeutic trials focusing on the combined NAFLD treatment, providing a link between the multiple-hit pathogenesis and the multimodal treatment of NAFLD patients. A diabetes-like therapeutic approach for NAFLD is finally proposed.

Serum homocysteine levels in patients with nonalcoholic fatty liver disease.

Background and rational for the study. Nonalcoholic fatty liver disease (NAFLD) is regarded as the hepatic component of insulin resistance (IR) syndrome, but data on serum homocysteine (HCY) are limited. The aim of the study was the evaluation of serum HCY levels in patients with NAFLD. Material and methods. Thirty-one patients (54 ± 11 years, 8 males) with biopsy-proven NAFLD, 15 with simple nonalcoholic fatty liver (NAFL) and 16 with nonalcoholic steatohepatitis (NASH), and 22 healthy controls (52 ± 9 years, 5 males) matched for gender, age and body mass index (BMI), were recruited. Blood samples for HCY, folate, vitamin B12, insulin and standard biochemical tests were obtained after overnight fasting. Homeostatic model of assessment-insulin resistance (HOMA-IR) was calculated. Results. There was no difference in mean serum HCY levels between controls and NAFLD patients (12.6 ± 4.6 vs. 13.5 ± 2.6 mmol/L, respectively; p = 0.432). Serum folate and vitamin B12 were also similar between the study groups. Mean age, BMI, serum folate and vitamin B12 did not differ between NAFL and NASH patients. However, when compared with NAFL patients, NASH patients had lower mean serum HCY levels (12.3 ± 2.5 vs. 14.7 ± 2.1 mmol/L; p = 0.006). HCY was lower by increasing the grading of fibrosis (p = 0.005), portal inflammation (p = 0.029) and steatosis location (p = 0.021). In logistic regression analysis, HCY independently predicted NASH (p = 0.045) after adjustment for gender, age, BMI, AST, glucose and HOMA-IR. Conclusion. Our data suggest that serum HCY levels are lower in NASH compared with NAFL patients and can independently predict NASH. Serum HCY might represent another non-invasive marker for the assessment of NAFLD.

Histological presence of Helicobacter pylori bacteria in the trabeculum and iris of patients with primary open-angle glaucoma.

PURPOSE: To investigate the role of Helicobacter pylori in primary open-angle glaucoma (POAG) pathophysiology by detecting its presence in eye biopsies of POAG patients during trabeculectomy. PATIENTS AND METHODS: Fifty-one consecutive patients who underwent trabeculectomy for POAG not responsive to antiglaucoma therapy, and 35 consecutive anemic controls were examined for H. pylori presence mainly by gastric mucosa histology. In POAG patients, eye biopsies were also obtained and stained for H. pylori presence in situ. RESULTS: Forty-three of 51 (84.3%) POAG patients and 17 of 35 (48.6%) controls were tested H. pylori positive (p = 0.0004). In 5 H. pylori-positive POAG patients, H. pylori bacteria were identified in the trabeculum and iris specimens. CONCLUSION: For the first time, H. pylori bacteria have been detected histologically in eye biopsies of POAG patients.

Serum vitamin B12 and folate levels in patients with non-alcoholic fatty liver disease.

The aim of the study was the evaluation of serum vitamin B12 and folate levels in patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD) and their association with the disease severity. Thirty patients with biopsy-proven NAFLD and 24 healthy controls matched for gender, age, body mass index and waist circumference were recruited. Blood samples for vitamin B12, folate, insulin and standard biochemical tests were obtained after overnight fasting. Homeostatic model of assessment-insulin resistance was calculated. There was no difference in serum vitamin B12 and folate levels between groups. Neither vitamin B12 nor folate levels were significantly different within any histological category, including steatosis grade, fibrosis stage, lobular inflammation, portal inflammation and ballooning. In conclusion, similar vitamin B12 and folate levels were observed in non-alcoholic steatohepatitis and non-alcoholic fatty liver patients, and controls. Furthermore, vitamin B12 and folate levels were not associated with either insulin resistance or the severity of liver disease.