miR-155 and miR-21 as Diagnostic and Therapeutic Biomarkers for Ulcerative Colitis: There Is Still a Long Way to Go.

(1) Elucidating the role of miRNAs (miRs) in ulcerative colitis may provide new insights into disease pathogenesis, diagnosis, treatment, and monitoring We aimed to investigate whether plasma levels of miR-21-5p and miR-155-5p may be used to differentiate between patients with organic disease such as ulcerative colitis (UC) and Clostridioides difficile infection (CDI), and patients with functional disease such as irritable bowel syndrome with diarrhea (IBS-D). (2) Serological samples were collected to quantify miR-155 and -21 expression, which was carried out through quantitative real-time polymerase chain reaction (qRT-PCR), from 84 patients: 34 with acute UC (group 1), 17 with CDI (group 2), and 33 with IBS-D (control group). (3) In this study, we found that the expression levels of miR-155-5p were almost the same for the two conditions and the control group (UC: 4.22 ± 1.61, CDI: 3.94 ± 1.62, IBS-D: 4.26 ± 1.26), with no significant differences either for ΔCt- or for ΔΔCt-derived parameters (p = 0.74 and p = 0.73, respectively). For miR-21, ΔCt levels presented significantly higher values among the ulcerative colitis group (p < 0.01), but the most important expression fold change was noticed in patients with CDI (UC:4.11 ± 8,46, CDI: 4.94 ± 9.68, IBS-D: 2.83 ± 5.41). (4) Circulating miR-155 and miR-21 were upregulated in UC, CDI, and IBS-D, but differentiation was not possible among them. But their involvement in the pathogenesis of the three diseases makes them suitable for improving the accuracy of diagnosis and facilitating the development of personalized treatment strategies.

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.

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.

Long-Term Radiological Pulmonary Changes in Mechanically Ventilated Patients with Respiratory Failure due to SARS-CoV-2 Infection.

From the first reports of SARS-CoV-2, at the end of 2019 to the present, the global mortality associated with COVID-19 has reached 6,952,522 deaths as reported by the World Health Organization (WHO). Early intubation and mechanical ventilation can increase the survival rate of critically ill patients. This prospective study was carried out on 885 patients in the ICU of Mureș County Clinical Hospital, Romania. After applying inclusion and exclusion criteria, a total of 54 patients were included. Patients were monitored during hospitalization and at 6-month follow-up. We analyzed the relationship between invasive mechanical ventilation (IMV) and non-invasive mechanical ventilation (NIMV) and radiological changes on thoracic CT scans performed at 6-month follow-up and found no significant association. Regarding paraclinical analysis, there was a statistically significant association between patients grouped by IMV and ferritin level on day 1 of admission (p = 0.034), and between patients grouped by PaO2/FiO2 ratio with metabolic syndrome (p = 0.03) and the level of procalcitonin (p = 0.01). A significant proportion of patients with COVID-19 admitted to the ICU developed pulmonary fibrosis as observed at a 6-month evaluation. Patients with oxygen supplementation or mechanical ventilation require dynamic monitoring and radiological investigations, as there is a possibility of long-term pulmonary fibrosis that requires pharmacological interventions and finding new therapeutic alternatives.

The Occurrence of Acute Disseminated Encephalomyelitis in SARS-CoV-2 Infection/Vaccination: Our Experience and a Systematic Review of the Literature.

BACKGROUND: The neurological complications of coronavirus disease 2019 (COVID-19) infection and the side effects of vaccination include immune-mediated diseases of the central nervous system (CNS) such as acute disseminated encephalomyelitis (ADEM). It is an acute-onset demyelinating disease that involves a rapid evolution and multifocal neurological deficits that develops following a viral or bacterial infection or, less frequently, following vaccination. Acute hemorrhagic leukoencephalitis (AHLE) is the hemorrhagic variant of ADEM that presents a more severe evolution which can be followed by coma and death. The objectives of this study consist in evaluating the diagnosis, clinical characteristics, imaging and laboratory features, evolution, and treatment of ADEM and AHLE following COVID-19 infection or vaccination. METHODS: We performed a systematic review of the medical literature according to PRISMA guidelines that included ADEM cases published between 1 January 2020 and 30 November 2022 following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination and also included our own clinical experience regarding this pathology. RESULTS: A total number of 74 patients were diagnosed with ADEM, 45 following COVID-19 infection and 29 after a SARS-CoV-2 vaccine. A total of 13 patients (17.33%) presented AHLE. The moderate form of COVID-19 presented a positive correlation with AHLE (r = 0.691, p < 0.001). The existence of coma and AHLE was correlated with poor outcomes. The following more aggressive immunomodulatory therapies applied in severe cases were correlated with poor outcomes (major sequelae and death): therapeutic plasma exchange (TPE) treatment (r = 382, p = 0.01) and combined therapy with corticosteroids and TPE (r = 0.337, p = 0.03). CONCLUSIONS: Vaccinations are essential to reduce the spread of the COVID-19 pandemic, and the monitoring of adverse events is an important part of the strategic fight against SARS-CoV-2. The general benefits and the overall good evolution outweigh the risks, and prompt diagnosis is associated with a better prognosis in these patients.

The Impact of Clostridioides Difficile Infection in Hospitalized Patients: What Changed during the Pandemic?

(1) Background: Clostridioides difficile (C. difficile) and SARS-CoV-2 coronavirus represent significant health threats. Our study focused on the impact of concurrent infections on patient outcomes against the backdrop of changes imposed by the pandemic. (2) Materials and methods. We performed a retrospective analysis and included patients diagnosed with CDI who were admitted in our hospital before and during the pandemic. We compared patient exposure to risk factors for CDI in both groups and patient negative outcomes: need for ICU care, prolonged hospitalization, organ failure, toxic megacolon, and death. (3) Results. Overall, 188 patients were included, of which 100 had CDI (the pre-pandemic group), and 88 patients presented both CDI and COVID-19 (the pandemic group). Patients in the pandemic group were significantly older, with a higher Charlson Comorbidity Index (CCI) and a greater exposure to antibiotics and corticosteroids, and were more likely to develop organ dysfunction, to require ICU care and have prolonged hospitalization. The severity of COVID-19, leukocytosis and increased D-dimer levels were indicators of poor prognosis in the pandemic group. Higher CCI scores and leukocytosis increased the risk for negative outcomes in CDI alone patients. (4) Conclusions. The study highlights the negative impact of associated infections on patient outcome. The severity of COVID-19 directly influences the prognosis of patients with concurrent infections.

SARS-CoV-2 associated liver injury: a six-month follow-up analysis of liver function recovery.

Background and aims: SARS-CoV-2 infection has raised the interest in clinical and paraclinical research worldwide, representing a public health issue since the beginning of 2020. Studies have established the variable, unpredictable character of COVID-19. Our main objective was to assess the liver function of patients without pre-existing liver disease, diagnosed with SARS-CoV-2 associated liver injury in a 6-month follow-up study after discharge from hospital. Methods: We conducted a prospective paraclinical and imagingstic follow-up study between 1st September 2020 and 30th April 2021 on patients without pre-existing liver disease previously diagnosed with SARS-CoV-2 associated liver injury who had been admitted in Mures County Clinical Hospital, Targu Mures, Romania. We followed up the patients 'clinical and paraclinical datacharacteristics at index COVID-19 hospitalization and at T1 (6-month follow-up visit). Results: We performed abdominal ultrasonography and laboratory examinations in 78 patients (mean age 45±10 years) hospitalized 6 months earlier for symptomatic COVID-19, with a male:female ratio of 1.3:1.Thirty patients (38.46%) were discharged at index COVID-19 hospitalization with abnormal liver function tests, while the rest presented paraclinical normalization at discharge and mean duration of liver injury of approximately 7 days. Follow-up examination revealed abnormal liver function tests in twenty-four patients, most of which presented with mild liver injury. All patients with severe COVID-19 at index hospitalization presented with abnormal liver function tests at follow-up examination. Conclusions: By performing a complete clinical and paraclinical 6-month follow-up study, with a specific focus on 34.6% of patients in which we noted a persistence of liver function tests abnormality, we could analyzse a possible long-term effect of SARS-CoV-2 infection over liver function and also raise awareness of liver function tests monitoring and therapeutic management in post COVID-19 patients. Long-term follow-up studies of COVID-19 multi-organ sequelae are therefore mandatory in order to improve the practice of consultant gastroenterologists.

Autoimmune Encephalitis in COVID-19 Infection: Our Experience and Systematic Review of the Literature.

The neurologic complications of COVID-19 infection are frequent in hospitalized patients; a high percentage of them present neurologic manifestations at some point during the course of their disease. Headache, muscle pain, encephalopathy and dizziness are among the most common complications. Encephalitis is an inflammatory condition with many etiologies. There are several forms of encephalitis associated with antibodies against intracellular neuronal proteins, cell surfaces or synaptic proteins, referred to as autoimmune encephalitis. Several case reports published in the literature document autoimmune encephalitis cases triggered by COVID-19 infection. Our paper first presents our experience in this issue and then systematically reviews the literature on autoimmune encephalitis that developed in the background of SARS-CoV-2 infections and also discusses the possible pathophysiological mechanisms of auto-immune-mediated damage to the nervous system. This review contributes to improve the management and prognosis of COVID-19-related autoimmune encephalitis.

Impact of the Severity of Liver Injury in COVID-19 Patients Admitted to an Intensive Care Unit During the SARS-CoV2 Pandemic Outbreak.

INTRODUCTION: The World Health Organization (WHO) identified a novel coronavirus, originating in Wuhan, China, in December 2019, as a pneumonia causing pathogen. Epidemiological data in Romania show more than 450.000 confirmed patients, with a constant number of approximately 10% admission in intensive care unit. METHOD: A retrospective, observational study was conducted from 1st March to 30th October 2020, comprising 657 patients, confirmed as having COVID-19, and who had been admitted to the intensive care unit of the Mures County Clinical Hospital, Tîrgu Mures, Romania, which had been designated as a support hospital during the pandemic. Patients who presented at admission or developed abnormal liver function tests in the first seven days of admission, were included in the study; patients with pre-existing liver disease, were excluded. RESULTS: The mean (SD) age of patients included in the study was 59.41 (14.66) years with a male: female ratio of 1.51:1. Survivor status, defined as patients discharged from the intensive care unit, was significantly associated with parameters such as age, leukocyte count, albumin level, glycaemia level (p<0.05 for all parameters.). CONCLUSIONS: Liver injury expressed through liver function tests cannot solely constitute a prognostic factor for COVID-19 patients, but its presence in critically ill patients should be further investigated and included in future guideline protocols.

High-dose intravenous immunoglobulins as a therapeutic option in critical illness polyneuropathy accompanying SARS-CoV-2 infection: A case-based review of the literature (Review).

The still ongoing COVID-19 pandemic has exposed the medical community to a number of major challenges. A significant number of patients require admission to intensive care unit (ICU) services due to severe respiratory, thrombotic and septic complications and require long-term hospitalization. Neuromuscular weakness is a common complication in critically ill patients who are treated in ICUs and are mechanically ventilated. This complication is frequently caused by critical illness myopathy (CIM) or critical illness polyneuropathy (CIP) and leads to difficulty in weaning from the ventilator. It is thought to represent an important neurologic manifestation of the systemic inflammatory response syndrome (SIRS). COVID-19 infection is known to trigger strong immune dysregulation, with an intense cytokine storm, as a result, the frequency of CIP is expected to be higher in this setting. The mainstay in the diagnosis of this entity beside the high level of clinical awareness is the electrophysiological examination that provides evidence of axonal motor and sensory polyneuropathy. The present article presents the case of a 54-year-old woman with severe COVID 19 infection who developed neuromuscular weakness, which turned out to be secondary to CIP and was treated successfully with a high dose of human intravenous immunoglobulins. Related to this case, we reviewed the relevant literature data regarding the epidemiology, pathophysiology and clinical features of this important complication and discussed also the treatment options and prognosis.

Guillain-Barré syndrome associated with Covid-19: A close relationship or just a coincidence? (Review).

Several neurological complications affecting the central and peripheral nervous system were described secondary to COVID-19 infection such as hyposmia, headache, nausea, impaired consciousness, psychosis, neurocognitive syndromes and even cerebrovascular accidents. The mechanism of these complications is not fully understood, but heterogenous mechanisms such as cytokine storm, secondary hypercoagulability and direct neurotropism of the virus are thought to be involved. Guillain-Barré syndrome is a heterogeneous disease that frequently follows a bacterial or viral infection. During the ongoing SARS-CoV-2 pandemic, several isolated case reports and case series have suggested an association between this viral infection and the occurrence of Guillain-Barré syndrome. The main mechanism of Guillain-Barré syndrome is probably post-viral dysregulation of the immune system generated by SARS-CoV-2. The clinical characteristics and disease evolution seem to be similar to those observed in Guillain-Barré syndrome secondary to other etiologies. The aim of the present review is to summarize the relevant literature regarding SARS-CoV-2-related Guillain-Barré syndrome.

Influence of GSTM1, GSTT1, and GSTP1 Polymorphisms on Type 2 Diabetes Mellitus and Diabetic Sensorimotor Peripheral Neuropathy Risk.

BACKGROUND AND AIMS: Diabetic neuropathy is a frequent complication of type 2 diabetes mellitus (T2DM). Genetic susceptibility and oxidative stress may play a role in the appearance of T2DM and diabetic neuropathy. We investigated the relation between polymorphism in genes related to oxidative stress such as GSTM1, GSTT1, and GSTP1 and the presence of T2DM and diabetic neuropathy (DN). METHODS: Samples were collected from 84 patients with T2DM (42 patients with DN and 42 patients without DN) and 98 healthy controls and genotyped by using polymerase chain reaction and restriction fragment length polymorphism method. RESULTS: GSTP1 Ile105Val polymorphism was associated with the risk of developing T2DM (p = 0.05) but not with the risk of developing DN in diabetic cases. GSTM1 and GSTT1 gene polymorphisms were associated with neither the risk of developing T2DM nor the risk of DN occurrence in diabetic patients. No association was observed between the patients with T2DM and DSPN (diabetic sensorimotor peripheral neuropathy) and T2DM without DSPN regarding investigated polymorphism. CONCLUSION: Our data suggest that GSTP1 gene polymorphisms may contribute to the development of T2DM in Romanian population. GSTM1, GSTT1, and GSTP1 gene polymorphisms are not associated with susceptibility of developing diabetic neuropathy in T2DM patients.

Narrow-band imaging with magnifying endoscopy for the evaluation of gastrointestinal lesions.

Narrow band imaging (NBI) endoscopy is an optical image enhancing technology that allows a detailed inspection of vascular and mucosal patterns, providing the ability to predict histology during real-time endoscopy. By combining NBI with magnification endoscopy (NBI-ME), the accurate assessment of lesions in the gastrointestinal tract can be achieved, as well as the early detection of neoplasia by emphasizing neovascularization. Promising results of the method in the diagnosis of premalignant and malignant lesions of gastrointestinal tract have been reported in clinical studies. The usefulness of NBI-ME as an adjunct to endoscopic therapy in clinical practice, the potential to improve diagnostic accuracy, surveillance strategies and cost-saving strategies based on this method are summarized in this review. Various classification systems of mucosal and vascular patterns used to differentiate preneoplastic and neoplastic lesions have been reviewed. We concluded that the clinical applicability of NBI-ME has increased, but standardization of endoscopic criteria and classification systems, validation in randomized multicenter trials and training programs to improve the diagnostic performance are all needed before the widespread acceptance of the method in routine practice. However, published data regarding the usefulness of NBI endoscopy are relevant in order to recommend the method as a reliable tool in diagnostic and therapy, even for less experienced endoscopists.