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.

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.

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.

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.

Mental health-related stigma discrimination and prejudices among Greek healthcare professionals.

Introduction: Research shows that mental health-related stigma, stereotypes, and prejudices have a negative impact on the patients themselves as well as on their families and social entourage. Healthcare professionals, whose expertise and professional ethos are historically acknowledged by public opinion, are expected to play a major role in combating discrimination against psychiatric patients. In this study, we aimed to assess the attitudes of Greek healthcare professionals toward mental illness and people suffering from it. Materials and methods: It is a non-interventional, analytic study, in which 479 health workers from a tertiary hospital in Thessaloniki, Greece, participated. Every single hospital service -except the personnel of the Psychiatric Clinic- was included in our study: from the cleaning service to the administrative staff and the auxiliary staff such as stretcher carriers, food and nutrition services' staff, and social workers, the nursing staff, and finally the attending physicians, taking into consideration that the psychiatric patient, from the moment he/she enters the hospital, consecutively gets in contact with every work grade of the healthcare establishment. Participants' attitudes concerning mental illness have been evaluated using the Opinions about Mental Illness Scale (OMI), the Social Distance Scale (SDS), and the Level of Contact Report (LCR-12). Results: Despite the high level of familiarity [as evaluated with LCR-12; mean score (µ): 8.82 ± 1.73], the employees displayed a rather poor willingness to interact with psychiatric patients (as measured with SDS; µ:11.68 ± 4.28), and endorsed significant prejudice toward individuals with mental disorders (assessed using OMI subscales; Social Discrimination µ: 22.99 ± 12.08, Social Restriction µ: 17.45 ± 9.07, Social Care µ: 21.04 ± 4.12, Social Integration µ: 16.38 ± 4.68, Etiology µ: 9.80 ± 4.95). Age and education stood out as the main determinants of participants' attitudes, with younger and highly educated participants to have shown a relatively refined profile. Conclusion: These results are not significantly improved compared to those of previous decades in Greek healthcare professionals and call for critical reflection and targeted stigma-reduction efforts.

EEG Network Analysis in Epilepsy with Generalized Tonic-Clonic Seizures Alone.

Many contradictory theories regarding epileptogenesis in idiopathic generalized epilepsy have been proposed. This study aims to define the network that takes part in the formation of the spike-wave discharges in patients with generalized tonic-clonic seizures alone (GTCSa) and elucidate the network characteristics. Furthermore, we intend to define the most influential brain areas and clarify the connectivity pattern among them. The data were collected from 23 patients with GTCSa utilizing low-density electroencephalogram (EEG). The source localization of generalized spike-wave discharges (GSWDs) was conducted using the Standardized low-resolution brain electromagnetic tomography (sLORETA) methodology. Cortical connectivity was calculated utilizing the imaginary part of coherence. The network characteristics were investigated through small-world propensity and the integrated value of influence (IVI). Source localization analysis estimated that most sources of GSWDs were in the superior frontal gyrus and anterior cingulate. Graph theory analysis revealed that epileptic sources created a network that tended to be regularized during generalized spike-wave activity. The IVI analysis concluded that the most influential nodes were the left insular gyrus and the left inferior parietal gyrus at 3 and 4 Hz, respectively. In conclusion, some nodes acted mainly as generators of GSWDs and others as influential ones across the whole network.

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.

Real-World Assessment of Quality of Life in Patients with Relapsing Remitting Multiple Sclerosis Treated with Teriflunomide for Two Years: Patient-Reported Outcomes from the AURELIO Study in Greece.

INTRODUCTION: Multiple sclerosis (MS) is a highly heterogeneous inflammatory disease of the central nervous system. Patient-reported outcomes (PROs) in a real-world clinical setting can provide detailed information about MS from the patient's perspective. PROs were used here to assess quality of life (QoL), treatment satisfaction, clinical efficacy, and safety outcomes in a Greek cohort of relapsing remitting MS (RRMS) patients treated with oral teriflunomide (14 mg/day). METHODS: AURELIO was a 2-year, prospective, observational study whose QoL primary endpoint was assessed with the Multiple Sclerosis Impact Scale (MSIS-29). Secondary endpoints included analyses of Patient Determined Disease Steps (PDDS), Treatment Satisfaction Questionnaire for Medication (TSQM), Expanded Disability Status Scale (EDSS), annualized relapse rate (ARR), adherence, and safety outcomes. RESULTS: AURELIO enrolled 282 patients (62.8% female; mean age 44.8 [SD ± 11] years; EDSS 2.0 [SD ± 1.6]; 44.6% treatment-naïve), with 212 patients (75%) remaining on treatment at study end. MSIS-29 total scores remained stable, while the MSIS-29 psychological scale showed significant improvement (p = 0.0015) at 2 years vs. baseline. TSQM scores at 2 years showed significant improvements in effectiveness (+ 6.6, p = 0.0001), convenience (+ 1.9, p = 0.0256), and global satisfaction (+ 8.1, p = 0.0001) vs. baseline. Disease progression was stable as indicated by non-significant changes in PDDS and EDSS vs. baseline. The ARR was low at 0.065, with a slightly higher ARR in previously treated (0.070) vs. naïve patients (0.058). Adherence was high at > 90%. Overall, 91 patients (32.3%) in the study reported a total of 215 safety events (32 serious, of which 21 were classified as mild-moderate). No new safety signals were observed. CONCLUSIONS: These data highlight the importance of PROs to facilitate personalized treatment strategies in MS. In line with other teriflunomide studies, AURELIO showed stable QoL, efficacy and safety outcomes, and good treatment satisfaction both in treatment-naïve and previously treated patients in this Greek cohort of patients with RRMS.

Impact of Helicobacter pylori-Related Metabolic Syndrome Parameters on Arterial Hypertension.

Arterial hypertension is a risk factor for several pathologies, mainly including cardio-cerebrovascular diseases, which rank as leading causes of morbidity and mortality worldwide. Arterial hypertension also constitutes a fundamental component of the metabolic syndrome. Helicobacter pylori infection is one of the most common types of chronic infection globally and displays a plethora of both gastric and extragastric effects. Among other entities, Helicobacter pylori has been implicated in the pathogenesis of the metabolic syndrome. Within this review, we illustrate the current state-of-the-art evidence, which may link several components of the Helicobacter pylori-related metabolic syndrome, including non-alcoholic fatty liver disease and arterial hypertension. In particular, current knowledge of how Helicobacter pylori exerts its virulence through dietary, inflammatory and metabolic pathways will be discussed. Although there is still no causative link between these entities, the emerging evidence from both basic and clinical research supports the proposal that several components of the Helicobacter pylori infection-related metabolic syndrome present an important risk factor in the development of arterial hypertension. The triad of Helicobacter pylori infection, the metabolic syndrome, and hypertension represents a crucial worldwide health problem on a pandemic scale with high morbidity and mortality, like COVID-19, thereby requiring awareness and appropriate management on a global scale.

Impact of Body Mass Index on the Age of Relapsing-Remitting Multiple Sclerosis Onset: A Retrospective Study.

A BACKROUND: Multiple sclerosis (MS) is a complex chronic disease of the central nervous system (CNS). Body mass index (BMI), a component of metabolic syndrome (MetS), is considered among the risk factors for MS. However, its role in MS remains ambiguous. OBJECTIVE: To examine the impact of BMI on the age of onset in patients with relapsing-remitting MS (RRMS) in a Greek cohort. METHODS: Data from 821 Greek patients with RRMS were collected. The BMI values were considered as quartiles. Comparisons for the demographic characteristics between the quartiles were made by Pearson's chi-square test for the categorical variables and by ANOVA for the continuous variables. An overall p-value was calculated corresponding to trend for association. In case of significant association, further post-hoc analysis was performed in order to identify differences in demographic characteristics between specific BMI quartiles groups. Linear regression analyses were used to assess the relationship between BMI and age at onset of MS. RESULTS: Comparisons of participant characteristics by quartiles of BMI revealed that participants with the highest BMI had an older age of disease onset. Results from linear regression analysis showed that with each increase of 1 BMI unit, the age of RRMS onset increases by 0.255 (95% CI 0.136 to 0.374) years, p < 0.001. CONCLUSIONS: Patients with higher BMI, as a parameter of MetS, exhibit increased age of RRMS onset. Our results may present an alternative personalized approach for diagnosis, prognosis, and/or prevention of RRMS.

Brain abscess in a rheumatoid arthritis patient treated with leflunomide - A case presentation and review.

BACKGROUND: Immunosuppression is a significant parameter in the pathogenesis of brain abscesses (BA) and it could be the result of severe infections such as acquired immunodeficiency syndrome or drug-induced, by several medications used for systemic autoimmune diseases. Leflunomide is a pyrimidine synthesis inhibitor that affects the proliferation of lymphocytes and is used as a disease-modifying antirheumatic drug. Mild infections, particularly those of the respiratory tract and herpes zoster, are one of its most common adverse effects. However, atypical and severe infections have also been reported under treatment with leflunomide. CASE DESCRIPTION: A 70-year old female was referred to our hospital with headache, aphasia, and right-sided hemiparesis and a lesion of the left parietal lobe initially interpreted as a malignancy. Her medical history revealed a 12-year old history of rheumatoid arthritis under current treatment with leflunomide. A cerebral magnetic resonance imaging (MRI) revealed typical findings for a BA. She subsequently underwent a left craniotomy, which confirmed the MRI-based diagnosis. The abscess was evacuated and cultures were obtained intraoperatively. In the postoperative examination, the patient showed no neurological deficit. CONCLUSION: The differential diagnostic considerations in immunocompromised patients with neurologic deficits should include focal central nervous system infections such as a BA, even in the absence of fever or immunosuppressant-induced leukopenia. It also demonstrates the importance of early neurosurgical intervention for the prevention of sequelae. To the best of our knowledge, this is the second-to-date reported case of a BA under immunomodulatory therapy with leflunomide.

The trimebutine effect on Helicobacter pylori-related gastrointestinal tract and brain disorders: A hypothesis.

The localization of bacterial components and/or metabolites in the central nervous system may elicit neuroinflammation and/or neurodegeneration. Helicobacter pylori (a non-commensal symbiotic gastrointestinal pathogen) infection and its related metabolic syndrome have been implicated in the pathogenesis of gastrointestinal tract and central nervous system disorders, thus medications affecting the nervous system - gastrointestinal tract may shape the potential of Helicobacter pylori infection to trigger these pathologies. Helicobacter pylori associated metabolic syndrome, by impairing gut motility and promoting bacterial overgrowth and translocation, might lead to brain pathologies. Trimebutine maleate is a prokinetic drug that hastens gastric emptying, by inducing the release of gastrointestinal agents such as motilin and gastrin. Likewise, it appears to protect against inflammatory signal pathways, involved in inflammatory disorders including brain pathologies. Trimebutine maleate also acts as an antimicrobial agent and exerts opioid agonist effect. This study aimed to investigate a hypothesis regarding the recent advances in exploring the potential role of gastrointestinal tract microbiota dysbiosis-related metabolic syndrome and Helicobacter pylori in the pathogenesis of gastrointestinal tract and brain diseases. We hereby proposed a possible neuroprotective role for trimebutine maleate by altering the dynamics of the gut-brain axis interaction, thus suggesting an additional effect of trimebutine maleate on Helicobacter pylori eradication regimens against these pathologies.

Helicobacter pylori infection as a potential risk factor for multiple sclerosis.

Helicobacter pylori infection (Hp-I) has been associated with a wide spectrum of gastrointestinal and extra-digestive manifestations, including neurodegenerative diseases. Contradictory data have been published on Hp-I and multiple sclerosis (MS) association, with studies mainly using serology for Hp-I detection that cannot distinguish between active and past infections. We herein hypothesize that humoral and cellular immune responses induced by active Hp-I, beyond damaging locally the gastric mucosa, they may shape the character of systemic autoimmune responses, contributing to MS pathogenesis. To investigate our hypothesis, active Hp-I has been diagnosed in two small MS Greek cohorts by using primarily gastric mucosa histology. A higher prevalence of active Hp-I was documented in MS patients vs. controls (86.4 vs. 50%, P = 0.002)accompanied by exclusive existence of duodenal ulcer and autoimmune diseases with endoscopic and histological findings of chronic active gastritis for the MS group. Our preliminary data suggested that active Hp-Iunlike other studies, may not protect, but contribute to MS and we proposed possibleHp-relating mechanisms involved in MS pathophysiology, that merit further evaluation.

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.

A perspective on risk factors for esophageal adenocarcinoma: emphasis on Helicobacter pylori infection.

Gastroesophageal reflux disease (GERD) and the increasing rate of its associated complications, including esophageal adenocarcinoma (EAC), has stimulated a plethora of studies attempting to evaluate provocative and protective factors. Helicobacter pylori (Hp) infection (Hp-I) was initially considered as a beneficial condition in GERD management based on rather limited data. Large-scale regional studies revealed an alternative approach, by suggesting a positive relationship between Hp-I and EAC development. Regarding pathophysiology, Hp-I induces gastric microbiota disturbances through hypochlorhydria and chronic inflammation, with a subsequent possible effect on the GERD-Barrett's esophagus (BE)-EAC cascade. Additionally, both direct effects on esophageal mucosa and indirect effects on known mechanisms of GERD, such as acid pocket and transient lower esophageal sphincter relaxation, remain to be elucidated. Hp contribution to carcinogenesis is related to oncogenic gastrin, cyclooxygenase-2, and prostaglandins; Ki-67 is also expressed and represents an index of BE-related malignancy. Moreover, Hp-I is vigorously suggested as a risk factor for metabolic syndrome, which may be the link between Hp-I and EAC. Although further studies are necessary to establish a pathophysiologic risk between Hp-I and the GERD-BE-EAC sequence, the theory of Hp protection against GERD seems outdated.

Body mass index in patients with Multiple Sclerosis: a meta-analysis.

Background: The impact of nutrition and diet on the etiology of Multiple Sclerosis (MS) has been evaluated through a number of studies. Only a limited number reported findings on the association between body mass index (BMI) and MS. We systematically assessed whether BMI differs between MS patients and healthy individuals. Methods: The PubMed database was searched for available studies assessing the relationship between BMI and MS until April 2018. Random effects models were applied for evaluating the association of mean BMI between MS, relapsing-remitting MS (RRMS) patients, females, or males with MS, and their respective healthy control groups. Results: We included 25 studies. The mean BMI of MS patients during the course of the disease and RRMS patients was significantly different from the mean BMI of their healthy counterpart individuals [standardized mean difference (SMD) (95% confidence interval (CI)): -0.25 (-0.44, -0.06), PZ = 0.01 and SMD (95%): -0.27 (-0.54, -0.01), PZ = 0.04, respectively]. The mean BMI of females with MS was significantly differentfrom that of corresponding healthy females [SMD (95% CI): -0.52 (-0.96, -0.07), PZ = 0.02]. Moreover, the mean BMI was significantly different between males with MS and healthy males [SMD (95% CI): -0.75 (-1.33, -0.18), PZ = 0.01]. Conclusions: Statistically significantly lower mean BMI was revealed in the overall MS patients' group during the MS course than in healthy controls. The same difference was revealed in all parts of the meta-analysis demonstrating a significantly lower BMI in patients with RRMS, in females, and in males with MS, when compared to their respective healthy individuals.

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.

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.