Case Report Myasthenia Gravis and Stroke in the Setting of Giant Cell Arteritis

This case report concerns the diagnosis of two independent chronic diseases in a patient hospitalized for stroke, myasthenia gravis (MG) and giant cell arteritis (GCA). MG has been found to be associated with several diseases, but there are very few cases documenting its coexistence with GCA. We report the case of a 79-year-old woman initially hospitalized for stroke. Patient's concurrent symptoms of blepharoptosis, dysphagia, and proximal muscle weakness were strongly suggestive of myasthenia gravis. The persistent low-grade fever and elevated inflammatory markers in combination with the visual deterioration that developed also raised the suspicion of GCA. Histological examination confirmed GCA, while muscle acetylcholine receptor antibodies were also present. Even though in medicine one strives to interpret a patient's symptoms with one diagnosis, when one entity cannot fully interpret the clinical and laboratory findings, clinicians must consider the possibility of a second coexisting illness

Investigation of the neuro-immunopharmacological tole of histamine in the hypothalamus

The relatively recently described alterations in the communication among the immune, nervous and endocrine systems, under various pathological conditions, drove biomedical research to the investigation of the structural, functional and pharmacological interactions amongst them. The neurotransmitter role of histamine in the central nervous system, in combination to its classical peripheral properties as a mediator of mast cells and of atopic and inflammatory responses point to the need for the investigation of its neuroimmunopharmacological role. The major source of histamine in the brain is the hypothalamus, where it is located both in neurons and in mast cells. Aiming at investigating the neuroimmunopharmacological role of hypothalamic histamine and its cellular origin that is likely to be involved in the observed changes under pathological situations, this study investigated the effect on the hypothalamic histamine levels of (i) substances that affect the activation of mast cells (ii) experimental models of arthritis and hyperthyroidism characterized by alterations of the circulating inflammatory mediators and impairment of the hypothalamic-pituitaryadrenal (HPA) and hypothalamic-pituitary-thyroid (HPT) axes. Histamine was quantified fluorometrically following its extraction from the rat hypothalamus with and without in vivo systemic administration of suitable pharmacologically active substances at various dosages. The results showed that the histamine levels in the hypothalamus of normal rats were 0.20-0.40 ng/mg tissue, significantly higher than those detected in other brain regions in accordance to the anatomical distribution of histamine in the brain. The reduction of the hypothalamic histamine levels upon various experimental treatments was attributed to the stress induced by them, independently of their characteristics. The presence and functionality of hypothalamic mast cells were confirmed by the (i) reduction of the hypothalamic histamine levels following administration of C48/80, codeine and substance P, that induce non immunological degranulation, and the partial inhibition of this action by the mast cell stabilizer sodium cromoglycate, (ii) rough cytological evaluation and (iii) induction of non immunological secretion of histamine by isolated hypothalamic mast cells. Furthermore, the alterations in histamine content following administration of the selective serotonin reuptake inhibitor fluoxetine indicated a direct or indirect interaction between histaminergic and serotoninergic circuits in the rat. In contrast, H4 receptors seemed not to be involved in the regulation of the hypothalamic histamine levels under physiological conditions. The reduced amine levels in experimental arthritis or experimental hyperthyroidism indicated the immunoneuroendocrine role of histamine in the hypothalamus. In the case of experimental hyperthyroidism, the inhibition of this reduction by sodium cromoglycate provided evidence for mast cell participation, while the partial increase to normal levels following dronedarone administration implied the involvement of TRα1 receptors in the underlying mechanisms. Finally, this study provided data supporting the participation of histamine and mast cells in the immunoneuroendocrine systems of the hypothalamus both in physiological and in pharmacologically modified conditions. Targeting the development and evaluation of therapeutic interventions in related pathological conditions, further investigation of the quantitative, functional and metabolic changes under pathological conditions and especially of the direct or indirect interactions between mast cells, histamine, thyroid hormones and regulatory factors of the HPA and HPT axes are proposed.Η σχετικά πρόσφατη ανάδειξη µεταβολών στην επικοινωνία του ανοσοποιητικού, νευρικού και ενδοκρινικού συστήµατος σε πολλές παθολογικές καταστάσεις ώθησε τη βιοϊατρική έρευνα στη διερεύνηση της δοµικής, λειτουργικής και φαρµακολογικής αλληλεπίδρασης µεταξύ των συστηµάτων αυτών. H νευροδιαβιβαστική δράση της ισταµίνης στο κεντρικό νευρικό σύστηµα, σε συνδυασµό µε τις κλασσικές περιφερικές ιδιότητες της ως µεσολαβητή των µαστοκυττάρων και της ατοπικής και φλεγµονώδους απάντησης υποδεικνύουν την ανάγκη διερεύνησης του νευροανοσοφαρµακολογικού της ρόλου. ?ς κύρια πηγή της ισταµίνης στον εγκέφαλο αναφέρεται ο υποθάλαµος, όπου εντοπίζεται τόσο σε νευρώνες όσο και σε µαστοκύτταρα. Με σκοπό τη µελέτη του νευροανοσοφαρµακολογικού ρόλου της ισταµίνης στον υποθάλαµο και κυρίως της κυτταρικής προέλευσής της, η οποία ενδεχοµένως εµπλέκεται στις παρατηρούµενες µεταβολές σε παθολογικό υπόστρωµα, διερευνήθηκε η επίδραση στα υποθαλαµικά επίπεδα ισταµίνης (i) ουσιών που δρουν στην ενεργοποίηση των µαστοκυττάρων (ii) πειραµατικών προτύπων αρθρίτιδας και υπερθυρεοειδισµού που χαρακτηρίζονται από µεταβολές των κυκλοφορούντων µεσο- λαβητών της φλεγµονής και από διαταραχές στους άξονες υποθαλάµου-υπόφυσης- επινεφριδίων (ΥΥΕ) και υποθαλάµου-υπόφυσης-θυρεοειδούς (ΥΥΘ). Ο ποσοτικός προσδιορισµός της ισταµίνης έγινε φθοριοφασµατοµετρικά µετά την αποµόνωση της από τον υποθάλαµο επιµυων, µετά ή χωρίς in vivo συστηµατική χορήγηση κατάλληλων φαρµακολογικώς δραστικών ουσιών, σε διάφορα δοσολογικά σχήµατα. Τα αποτελέσµατα έδειξαν ότι τα επίπεδα της ισταµίνης στον υποθάλαµο φυσιολογικών επιµυων ήταν 0,20-0,40 ng/mg ιστού, σηµαντικά υψηλότερα αυτών που ανιχνεύθηκαν σε άλλες εγκεφαλικές περιοχές, ακολουθώντας την ανατοµική κατανοµή των πηγών ισταµίνης στον εγκέφαλο. Η µείωση των επιπέδων στον υποθάλαµο κατά τους πειραµατικούς χειρισµούς αποδόθηκε στο στρες που προκλήθηκε από αυτούς, ανεξαρτήτως της φύσης τους. Η παρουσία και η λειτουργικότητα των υποθαλαµικών µαστοκυττάρων επιβεβαιώθηκαν από την (i) ελάττωση των επιπέδων ισταµίνης στον υποθάλαµο µετά από χορήγηση C48/80, κωδεΐνης και ουσίας P, που προκαλούν µη ανοσολογικής αιτιολογίας αποκοκκίωση, και µερική αναστολή της δράσης αυτής από τη χρωµολύνη, σταθεροποιητή της µαστοκυτταρικής µεµβράνης, (ii) αδρή κυτταρολογική εκτίµηση και (iii) πρόκληση µη ανοσολογικής αιτιολογίας απελευθέρωσης ισταµίνης σε αποµονωθέντα υποθαλαµικά µαστοκύτταρα. Επιπλέον, η µεταβολή των επιπέδων ισταµίνης µετά τη χορήγηση φλουοξετίνης, αναστολέα της επαναπρόσληψης σεροτονίνης, ανέδειξε άµεση ή έµµεση αλληλεπίδραση µεταξύ ισταµινεργικών και σεροτονινεργικών συστηµάτων στον επίµυ. Αντίθετα, οι Η4 υποδοχείς δε φάνηκε να εµπλέκονται στη ρύθµιση των επιπέδων ισταµίνης στον υποθάλαµο σε φυσιολογικές συνθήκες. Η µείωση των επιπέδων µετά την εγκατάσταση πειραµατικής αρθρίτιδας ή πειραµατικού υπερθυρεοειδισµού έδωσαν ενδείξεις για τον ανοσονευροενδοκρινικό ρόλο της ισταµίνης στον υποθάλαµο. Στον πειραµατικό υπερθυρεοειδισµό, η αναστολή της µείωσης αυτής από τη χρωµολύνη ανέδειξε τη συµµετοχή των µαστοκυττάρων, ενώ η µερική επαναφορά στα φυσιολογικά επίπεδα µετά από τη χορήγηση δρονεδαρόνης υποδήλωσε τη συµµετοχή των TRα1 υποδοχέων στους υποκείµενους µηχανισµούς. Τέλος, η µελέτη συνέβαλε στη συλλογή δεδοµένων που υποστηρίζουν τη συµµετοχή της ισταµίνης και των µαστοκυττάρων στα ανοσονευροενδοκρινικά συστήµατα στον υποθάλαµο, τόσο σε φυσιολογικό όσο και σε φαρµακολογικώς τροποποιηµένο υπόστρωµα. Με προοπτική την ανάπτυξη και αξιολόγηση θεραπευτικής παρέµβασης σε σχετιζόµενες παθολογικές καταστάσεις, προτείνεται η περαιτέρω διερεύνηση ποσοτικών, λειτουργικών και µεταβολικών αλλαγών σε παθολογικό υπόστρωµα, ιδιαιτέρως της άµεσης ή έµµεσης αλληλεπίδρασης υποθαλαµικών µαστοκυττάρων, ισταµίνης, θυρεοειδικών ορµονών και ρυθµιστικών παραγόντων των αξόνων ΥΥΕ και ΥΥΘ. 14

The Complex Interplay between Immunonutrition, Mast Cells, and Histamine Signaling in COVID-19

There is an ongoing need for new therapeutic modalities against SARS-CoV-2 infection. Mast cell histamine has been implicated in the pathophysiology of COVID-19 as a regulator of proinflammatory, fibrotic, and thrombogenic processes. Consequently, mast cell histamine and its receptors represent promising pharmacological targets. At the same time, nutritional modulation of immune system function has been proposed and is being investigated for the prevention of COVID-19 or as an adjunctive strategy combined with conventional therapy. Several studies indicate that several immunonutrients can regulate mast cell activity to reduce the de novo synthesis and/or release of histamine and other mediators that are considered to mediate, at least in part, the complex pathophysiology present in COVID-19. This review summarizes the effects on mast cell histamine of common immunonutrients that have been investigated for use in COVID-19

COVID-19 Disease and Outcomes among Critically Ill Patients: The Case of Medical Nutritional Therapy

The recent COVID-19 pandemic, which resulted from SARS CoV-2 coronavirus infection, contributed toa rapid increasein hospital and intensive care unit (ICU) admissions [...

DETERMINING THE BENDING AND TENSILE STRENGTH OF IMPREGNATED WITH RAPESEED OIL EUROPEAN BEECH (FAGUS SYLVATICA) WOOD JOINTS GLUED WITH PVAc AND PU

Abstract The objective of this study was to examine bending and tensile strength of beech wood (Fagus sylvatica

Incorporating Biomarkers in COPD Management: The Research Keeps Going

Globally, chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality, having a significant socioeconomic effect. Several molecular mechanisms have been related to COPD including chronic inflammation, telomere shortening, and epigenetic modifications. Nowadays, there is an increasing need for novel therapeutic approaches for the management of COPD. These treatment strategies should be based on finding the source of acute exacerbation of COPD episodes and estimating the patient’s own risk. The use of biomarkers and the measurement of their levels in conjunction with COPD exacerbation risk and disease prognosis is considered an encouraging approach. Many types of COPD biomarkers have been identified which include blood protein biomarkers, cellular biomarkers, and protease enzymes. They have been isolated from different sources including peripheral blood, sputum, bronchoalveolar fluid, exhaled air, and genetic material. However, there is still not an exclusive biomarker that is used for the evaluation of COPD but rather a combination of them, and this is attributed to disease complexity. In this review, we summarize the clinical significance of COPD-related biomarkers, their association with disease outcomes, and COPD patients’ management. Finally, we depict the various samples that are used for identifying and measuring these biomarkers

The impact of body mass index on post resuscitation survival after cardiac arrest: A meta-analysis

Background: Observational studies examining the association between body mass index (BMI) and the outcome of cardiac arrest (CA) shows controversial results. Methods: We reviewed literature for studies assessing the impact of BMI on survival and neurological outcome following CA. Eligible studies were subsequently meta-analyzed and pooled odds ratios and their corresponding 95% confidence intervals for post CA survival and neurological status were derived. Results: A total of 7 studies with 24,651 patients were evaluable for this meta-analysis. The studies were also categorized by location of the CA and the use of therapeutic hypothermia. Our results suggested that BMI between 25 and 29.9 kgr/m2had a favorable impact on survival after CA (OR = 1.172, 95% CI, 1.109-1.236) in comparison to normal weight subjects. Likewise, overweight patients presented increased odds for a favorable neurological outcome after CA (OR = 1.112, 95% CI, 1.020-1.213). On the contrary, underweight subjects presented decreased odds of surviving after CA as compared to normal BMI subjects (OR = 0.781, 95% CI, 0.652-0.935). Finally, BMI >30 kgr/m2was not associated with improved survival or neurological outcome as compared to BMI 18.5-24.9 kgr/m2. Conclusions: Overweight patients have a favorable prognosis after CA in terms of both survival and neurological outcome. This effect was amplified when the analysis is restricted in in-hospital cardiac arrest and in patients non-treated with therapeutic hypothermia

Global Leadership Initiative on Malnutrition Criteria Predict Pulmonary Complications and 90-Day Mortality after Major Abdominal Surgery in Cancer Patients

Although several studies have reported an association between malnutrition and the risk of severe complications after abdominal surgery, there have been no studies evaluating the use of Global Leadership Initiative on Malnutrition (GLIM) criteria for predicting postoperative pulmonary complications (PPCs) following major abdominal surgery in cancer patients. This study aimed to investigate the association among the diagnosis of malnutrition by GLIM criteria, PPCs risk and 90-day all-cause mortality rate following major abdominal surgery in cancer patients. We prospectively analyzed 218 patients (45% male, mean age 70.6 ± 11.2 years) with gastrointestinal cancer who underwent major abdominal surgery at our hospital between October 2018 and December 2019. Patients were assessed preoperatively using GLIM criteria of malnutrition, and 90-day all-cause mortality and PPCs were recorded. In total, 70 patients (32.1%) were identified as malnourished according to GLIM criteria, of whom 41.1% fulfilled the criteria for moderate and 12.6% for severe malnutrition. PPCs were detected in 48 of 218 patients (22%) who underwent major abdominal surgery. Univariate logistic regression analysis revealed that the diagnosis of malnutrition was significantly associated with the risk of PPCs. Furthermore, in multivariate model analysis adjusted for other clinical confounding factors, malnutrition remained an independent factor associated with the risk of PPCs (RR = 1.82; CI = 1.21–2.73) and 90-day all-cause mortality (RR = 1.97; CI = 1.28–2.63, for severely malnourished patients). In conclusion, preoperative presence of malnutrition, diagnosed by the use of GLIM criteria, is associated with the risk of PPCs and 90-day mortality rate in cancer patients undergoing major abdominal surgery

Does Route of Full Feeding Affect Outcome among Ventilated Critically Ill COVID-19 Patients: A Prospective Observational Study

The outbreak of the new coronavirus strain SARS-CoV-2 (COVID-19) highlighted the need for appropriate feeding practices among critically ill patients admitted to the intensive care unit (ICU). This study aimed to describe feeding practices of intubated COVID-19 patients during their second week of hospitalization in the First Department of Critical Care Medicine, Evaggelismos General Hospital, and evaluate potential associations with all cause 30-day mortality, length of hospital stay, and duration of mechanical ventilation. We enrolled adult intubated COVID-19 patients admitted to the ICU between September 2020 and July 2021 and prospectively monitored until their hospital discharge. Of the 162 patients analyzed (52.8% men, 51.6% overweight/obese, mean age 63.2 ± 11.9 years), 27.2% of patients used parenteral nutrition, while the rest were fed enterally. By 30 days, 34.2% of the patients in the parenteral group had died compared to 32.7% of the patients in the enteral group (relative risk (RR) for the group receiving enteral nutrition = 0.97, 95% confidence interval = 0.88–1.06, p = 0.120). Those in the enteral group demonstrated a lower duration of hospital stay (RR = 0.91, 95% CI = 0.85-0.97, p = 0.036) as well as mechanical ventilation support (RR = 0.94, 95% CI = 0.89–0.99, p = 0.043). Enteral feeding during second week of ICU hospitalization may be associated with a shorter duration of hospitalization and stay in mechanical ventilation support among critically ill intubated patients with COVID-19