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Autoimmune thyroid disease (AITD) is the leading cause of thyroid dysfunction globally, characterized primarily by two distinct clinical manifestations: Hashimoto's thyroiditis (HT) and Graves' disease (GD). The prevalence of AITD is approximately twice as high in women compared to men, with a particularly pronounced risk during the reproductive years. Pregnancy exerts profound effects on thyroid physiology and immune regulation due to hormonal fluctuations and immune adaptations aimed at fostering maternal-fetal tolerance, potentially triggering or exacerbating AITD. The impact of AITD on pregnancy outcomes is multifaceted. Both HT and GD have been associated with adverse obstetric and neonatal outcomes, including miscarriage, preterm delivery, preeclampsia and fetal growth restriction. Inadequately managed AITD can also affect fetal neurodevelopment due to disrupted maternal thyroid hormone availability during critical periods of brain maturation. This review explores the complex interplay between the genetic, epigenetic and environmental factors that drive AITD during pregnancy, highlighting their roles in disease development and impacts on pregnancy outcomes. Gaining a deeper understanding of these mechanisms is crucial for improving diagnostic tools, treatment options and preventive measures to enhance the health and well-being of both the mother and the newborn.

Maintaining the physiological function of the vascular endothelium and endothelial glycocalyx is crucial for the prevention of cardiovascular disease, which is one of the leading causes of morbidity and mortality worldwide. Damage to these structures can lead to atherosclerosis, hypertension, and other cardiovascular problems, especially in individuals with risk factors such as diabetes and obesity. Endothelial dysfunction is associated with ischemic disease and has a negative impact on overall cardiovascular health. The aim of this review was to comprehensively summarize the crucial role of the vascular endothelium and glycocalyx in cardiovascular health and associated thrombo-inflammatory conditions. It highlights how endothelial dysfunction, influenced by factors such as diabetes, chronic kidney disease, and obesity, leads to adverse cardiovascular outcomes, including heart failure. Recent evidence suggests that hyperbaric oxygen therapy (HBOT) may offer therapeutic benefits in the treatment of cardiovascular risk factors and disease. This review presents the current evidence on the mechanisms by which HBOT promotes angiogenesis, shows antimicrobial and immunomodulatory effects, enhances antioxidant defenses, and stimulates stem cell activity. The latest findings on important topics will be presented, including the effects of HBOT on endothelial dysfunction, cardiac function, atherosclerosis, plaque stability, and endothelial integrity. In addition, the role of HBOT in alleviating cardiovascular risk factors such as hypertension, aging, obesity, and glucose metabolism regulation is discussed, along with its impact on inflammation in cardiovascular disease and its potential benefit in ischemia-reperfusion injury. While HBOT demonstrates significant therapeutic potential, the review also addresses potential risks associated with excessive oxidative stress and oxygen toxicity. By combining information on the molecular mechanisms of HBOT and its effects on the maintenance of vascular homeostasis, this review provides valuable insights into the development of innovative therapeutic strategies aimed at protecting and restoring endothelial function to prevent and treat cardiovascular diseases.

Since its introduction, the number of heart surgeries has risen continuously. It is a high-risk procedure, usually involving cardiopulmonary bypass, which is associated with an inflammatory reaction that can lead to perioperative and postoperative organ dysfunction. The extent of complications following cardiac surgery has been the focus of interest for several years because of their impact on patient outcomes. Recently, numerous scientific efforts have been made to uncover the complex mechanisms of interaction between inflammation, oxidative stress, and endothelial dysfunction that occur after cardiac surgery. Numerous factors, such as surgical and anesthetic techniques, hypervolemia and hypovolemia, hypothermia, and various drugs used during cardiac surgery trigger the development of systemic inflammatory response and the release of oxidative species. They affect the endothelium, especially endothelial glycocalyx (EG), a thin surface endothelial layer responsible for vascular hemostasis, its permeability and the interaction between leukocytes and endothelium. This review highlights the current knowledge of the molecular mechanisms involved in endothelial dysfunction, particularly in the degradation of EG. In addition, the major inflammatory events and oxidative stress responses that occur in cardiac surgery, their interaction with EG, and the clinical implications of these events have been summarized and discussed in detail. A better understanding of the complex molecular mechanisms underlying cardiac surgery, leading to endothelial dysfunction, is needed to improve patient management during and after surgery and to develop effective strategies to prevent adverse outcomes that complicate recovery.

The endothelial glycocalyx (EGC) is a layer of proteoglycans (associated with glycosaminoglycans) and glycoproteins, which adsorbs plasma proteins on the luminal surface of endothelial cells. Its main function is to participate in separating the circulating blood from the inner layers of the vessels and the surrounding tissues. Physiologically, the EGC stimulates mechanotransduction, the endothelial charge, thrombocyte adhesion, leukocyte tissue recruitment, and molecule extravasation. Hence, severe impairment of the EGC has been implicated in various pathological conditions, including sepsis, diabetes, chronic kidney disease, inflammatory disorders, hypernatremia, hypervolemia, atherosclerosis, and ischemia/reperfusion injury. Moreover, alterations in EGC have been associated with altered responses to therapeutic interventions in conditions such as cardiovascular diseases. Investigation into the function of the glycocalyx has expanded knowledge about vascular disorders and indicated the need to consider new approaches in the treatment of severe endothelial dysfunction. This review aims to present the current understanding of the molecular mechanisms underlying cardiovascular diseases and to elucidate the impact of heart surgery on EGC dysfunction.

Background and Objectives: General anesthesia induces reversible unconsciousness, eliminating sensation and enabling painless medical procedures. Vital for dental care, it addresses patients with medical conditions, those needing extensive procedures, and those unable to cooperate due to fear. Dental care for patients with disabilities is a significant unmet need, with studies showing increased oral disease prevalence. This research aims to analyze postoperative morbidity both in healthy and disabled children undergoing dental procedures under general anesthesia. Materials and Methods: This study involved 96 children aged 3 to 15 with dental caries. Two groups were formed: the control group (CTL) (52.94%) included healthy patients requiring general anesthesia due to unsatisfactory cooperation, and the other group included children with physical or intellectual disabilities (CD) (47.96%). Postoperative complications were monitored 1 h after the procedure and 1, 3, 7, and 14 days after the procedure by contacting parents/caregivers by phone. The intensity of postoperative pain was assessed using the Wong-Baker faces pain rating scale. General anesthesia was conducted following a standardized protocol for dental procedures. Results: CTL patients complained more often about postoperative pain 1 h after the procedure ( p = 0.03). One day after the procedure, oral bleeding ( p = 0.04), fever ( p = 0.009), and diarrhea ( p = 0.037) occurred more often in CD. In the same period, sore throat appeared more often in CTL ( p = 0.036). Three days after the dental treatment, there were statistically significant increases in the occurrence of agitation ( p = 0.043) and constipation ( p = 0.043) in CD. Seven days later, CD demonstrated a higher occurrence of agitation ( p = 0.037). According to the Wong-Baker faces pain rating scale, CTL experienced more frequent and intense pain. Conclusions: CD more frequently reported complications like oral bleeding, fever, and diarrhea. In contrast, the CTL group more often reported pain-related symptoms. The conclusion underscores the need for a pain control protocol for CD and emphasizes the importance of frequent monitoring to prevent unwanted consequences during tooth restoration under general anesthesia.

Autoimmune thyroid disease (AITD) is the most common organ-specific autoimmune disorder clinically presented as Hashimoto thyroiditis (HT) and Graves' disease (GD). The pathogenesis of AITD is caused by an inappropriate immune response related to genetic, non-genetic, and environmental factors. Pregnancy is one of the factors that have a great influence on the function of the thyroid gland because of the increased metabolic demand and the effects of hormones related to pregnancy. During pregnancy, an adaptation of the maternal immune system occurs, especially of the innate immune system engaged in maintaining adaptive immunity in the tolerant state, preventing the rejection of the fetus. Pregnancy-related hormonal changes (estrogen, progesterone, hCG) may modulate the activity of innate immune cells, potentially worsening the course of AITD during pregnancy. This especially applies to NK cells, which are associated with exacerbation of HD and GD. On the other hand, previous thyroid disorders can affect fertility and cause adverse outcomes of pregnancy, such as placental abruption, spontaneous abortion, and premature delivery. Additionally, it can cause fetal growth retardation and may contribute to impaired neuropsychological development of the fetus. Therefore, maintaining the thyroid equilibrium in women of reproductive age and in pregnant women is of the highest importance.

Cardiac surgery is one of the highest-risk procedures, usually involving cardiopulmonary bypass and commonly inducing endothelial injury that contributes to the development of perioperative and postoperative organ dysfunction. Substantial scientific efforts are being made to unravel the complex interaction of biomolecules involved in endothelial dysfunction to find new therapeutic targets and biomarkers and to develop therapeutic strategies to protect and restore the endothelium. This review highlights the current state-of-the-art knowledge on the structure and function of the endothelial glycocalyx and mechanisms of endothelial glycocalyx shedding in cardiac surgery. Particular emphasis is placed on potential strategies to protect and restore the endothelial glycocalyx in cardiac surgery. In addition, we have summarized and elaborated the latest evidence on conventional and potential biomarkers of endothelial dysfunction to provide a comprehensive synthesis of crucial mechanisms of endothelial dysfunction in patients undergoing cardiac surgery, and to highlight their clinical implications.

Lichen planus is a chronic disease affecting the skin, appendages, and mucous membranes. A cutaneous lichen planus is a rare disease occurring in less than 1% of the general population, while oral illness is up to five times more prevalent; still, both forms equally impair the patient's quality of life. The etiology of lichen planus is not entirely understood. Yet, immune-mediated mechanisms have been recognized since environmental factors such as hepatitis virus infection, mechanical trauma, psychological stress, or microbiome changes can trigger the disease in genetically susceptible individuals. According to current understanding, lichen planus immunopathogenesis is caused by cell-mediated cytotoxicity, particularly cytotoxic T lymphocytes, whose activity is further influenced by Th1 and IL-23/Th-17 axis. However, other immunocytes and inflammatory pathways complement these mechanisms. This paper presents a comprehensive insight into the actual knowledge about lichen planus, with the causal genetic and environmental factors being discussed, the immunopathogenesis described, and the principal effectors of its inflammatory circuits identified.

Bilateral COVID-19 pneumonia is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and usually leads to life-threatening acute respiratory distress syndrome (ARDS). Treatment of patients with ARDS is difficult and usually involves protective mechanical ventilation and various types of recruitment maneuvers. A segmental lung recruitment maneuver by independent lung ventilation has been described as a successful recruitment maneuver in patients with lobar pneumonia, and may, therefore, be useful for the treatment of patients with bilateral COVID-19 pneumonia complicated by ARDS in the critical phase of the disease when all other therapeutic options have been exhausted. The aim of this case series was to present a case report of four mechanically ventilated patients with severe bilateral COVID-19 pneumonia complicated by ARDS using the segmental lung recruitment maneuver. The effect of the segmental lung recruitment maneuver was assessed by the increase in PaO 2 /FiO 2 ratio and the lung ultrasound (LUS) scoring system (0 points-presence of sliding lungs with A-lines or one or two isolated B-lines; 1 point-moderate loss of lung ventilation with three to five B lines; 2 points-severe loss of lung ventilation with more than five B lines (B pattern); and 3 points-lung consolidation) determined 12, 24, and 48 h after segmental lung recruitment. In three of four patients with bilateral COVID-19 pneumonia complicated by ARDS, an increase in the PaO 2 /FiO 2 ratio and an improvement in the LUS scoring system were observed 48 h after segmental lung recruitment. In conclusion, the segmental lung recruitment maneuver in patients with bilateral COVID-19 complicated by ARDS is an effective method of lung recruitment and may be a useful treatment method.

Psoriasis is a recurrent, chronic, immune-mediated, systemic inflammatory disease of the skin, joints, and other organic systems. After atopic dermatitis, chronic stationary psoriasis is the most common inflammatory skin disease, affecting an average of 2-4% of the world's population. The disease carries a significant burden due to its numerous comorbidities and the major impact on patients' social and emotional aspects of life. According to current knowledge, psoriasis is a multifactorial disease that occurs in genetically predisposed individuals under various environmental factors, which trigger an immune response disorder with a series of complex inflammatory cascades. The disease is initiated and maintained by mutual interaction of the innate and adaptive immune cells, primarily dendritic cells, T lymphocytes, and keratinocytes, whose leading role alternates at different stages of the disease, consisting mainly in the IL-23/Th17 pathway. Inflammatory events result in consequent epidermal and dermal changes and evolution of the characteristic psoriatic phenotype, respectively. This paper aims to present a comprehensive overview of current knowledge on psoriasis genetic and environmental etiological factors, immunopathogenesis, and the leading cellular and cytokine participants in the inflammatory pathways of this disease.

Aim: To compare the effect of adjunctive lidocaine-based scalp block and laryngotracheal local anesthesia vs general anesthesia only on pro-inflammatory cytokine concentrations in patients with non-ruptured brain aneurysms undergoing elective open surgery., Methods: This parallel, randomized, controlled, open-label trial was conducted at Clinical Hospital Center Zagreb between March 2019 and March 2020. At the beginning of anesthesia, lidocaine group received 40 mg of 2% lidocaine for laryngotracheal topical anesthesia and 4 mg/kg for the scalp block. Control group underwent general anesthesia only. Plasma concentrations of IL-6, TNF-α, and IL-1β were measured before anesthesia (S0); at the incision (S1); at the end of surgery (S2); 24 hours postoperatively (S3). Cerebrospinal fluid (CSF) cytokine concentrations were measured at the incision (L1) and the end of surgery (L2)., Results: Forty patients (each group, 20) were randomized; 37 were left in the final analysis. IL-6 plasma concentrations increased significantly compared with baseline at S3 in lidocaine group, and at S2 and S3 in control group. In both groups, changes in TNF-α and IL-1β were not significant. CSF cytokine concentrations in lidocaine group did not change significantly; in control group IL-6 and IL-1β were significantly higher at L2 than at L1. CSF IL-6 in control group significantly increased at L2, but TNF-α and IL-1β did not. No differences in clinical outcome and complication rates were observed., Conclusion: Adjunctive lidocaine-based scalp block and laryngotracheal local anesthesia might attenuate CSF IL-6 concentration increase in patients with brain aneurysm.

Lichen planus is a chronic mucocutanous disorder histopathologically characterized with a keratinocytes apoptosis, subsequent basal cell layer liquefaction and accumulation of the inflammatory infiltrate in papillary dermis. A formation of apoptotic bodies in basal cell layer is due to a cytotoxic lymphocyte attack to the basal keratinocytes. It has been demonstrated that the cytotoxic molecules included in this attack are perforin and granzyme B. Both molecules are found upregulated in CD8+ lymphocytes that are in close contact to keratinocytes. However, their amount is lower in lichen planus than in other skin disease characterized by liquefaction and vacuolar degeneration of the basal epidermal layer. This could speculate about other cytotoxic molecule such as granulysin that could mediate keratinocyte apoptosis. Therefore, in this article we hypothesize about the crucial role of granulysin molecule in keratinocytes killing that could contribute to a lichen planus pathogenesis., (Copyright © 2021. Published by Elsevier Ltd.)

It is increasingly recognized that modulation of brain inflammation may uncover new potential therapeutic strategies for stroke. Recent studies have shifted focus from immunological implications in ischemic stroke to a more devastating form; the hemorrhagic stroke.The aim of this study was to investigate the neuroinflammatory response in cerebrospinal fluid in patients with primary intracerebral hemorrhage (ICH) associated with intraventricular hemorrhage (IVH) in the presence of low-dose recombinant tissue plasminogen activator (rt-PA).This retrospective study included 88 adults with primary ICH associated with IVH. Patients were divided into 2 groups: rt-PA group and non-rt-PA group, which received normal standard of care for this diagnosis. The rt-PA group was treated via catheter-based clot lysis using low-dose rt-PA injected through the external ventricular drain (EVD) system, and the non-rt-PA group was treated with saline applied to EVD system in equivalent volume. Cerebrospinal fluid samples from rt-PA were obtained from the EVD system at 4 time points: once before the drug administration, and then on day 1, 3, and 7. No attempt at randomization was made. The decision to inject rt-PA was based on the preference of the primary attending neurologist and the ability to obtain consent. Temporal interleukin-1 beta and transforming growth factor beta concentration changes were analyzed and compared between the 2 groups.The concentration of interleukin-1 beta was significantly lower in the rt-PA group than in the non-rt-PA group on day 7. In addition, the concentration of transforming growth factor beta was significantly higher in the rt-PA group than in the non-rt-PA group on day 1. There was a significant difference in interleukin-1 beta concentration between days 0 and 1 in comparison to day 3 in the rt-PA group, and between day 0 in comparison to day 3 and 7 in the non-rt-PA group. We also observed a significant difference in transforming growth factor beta concentration between days 0 and 1 and between days 3 and 7.The different pattern of pro- and anti-inflammatory cytokines in patients with ICH associated with IVH suggest distinct characteristics of secondary brain injury depending on the treatment modality.

Modic changes (MCs) have attracted great interest in recent years. The complex process of MC development and progression seems to involve interplay between mechanical, infective, inflammatory, and degenerative processes that cannot be clearly differentiated. Based on signal intensity on T1- and T2-weighted MRI scans, MCs can be divided three types: Type 1, Type 2, and Type 3. Predominantly Type 1 MCs are commonly associated with chronic low back pain that is unresponsive to classic treatment options. Infection with low-virulent anaerobic microorganisms, most commonly Propionibacterium acnes, has been implicated in MC development following a disc herniation when a tear enables bacteria to enter the disc. Recent studies in patients with chronic low back pain following a lumbar disc herniation associated with Type 1 MCs have reported promising results following prolonged systemic antibiotic treatment with amoxicillin-clavulanate. Hyperbaric oxygen therapy, as primary or adjuvant treatment in association combination with systemic antibiotics or anti-inflammatory therapy, could offer important advantages in treating patients with suspected low-virulent disc infections due to anaerobic microorganisms associated with Type 1 MCs. We believe that hyperbaric oxygenation could contribute to faster resolution of Type 1 MCs and associated pain through multiple effects-including direct antimicrobial effects through formation of reactive oxygen species (ROS), altering the favorable low oxygen tension milieu such that it becomes unfavorable for bacterial growth and survival, and anti-biofilm effects. Additionally, hyperbaric oxygenation could contribute to faster pain resolution via direct and indirect anti-inflammatory effects. As an adjuvant treatment administered in combination with systemic antibiotics, HBOT could increase the sensitivity of Propionibacterium acnes to antimicrobial drugs under hyperoxic conditions, resulting in faster MC resolution. Overall, the faster infection resolution, diminished bacterial load, and anti-inflammatory effects due to reduced cytokine expression and levels of infectious by-products could lead to faster pain resolution following HBOT, and a significant improvement of quality of life in these patients., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Cerebral aneurysm surgery has significant mortality and morbidity rate. Inflammation plays a key role in the pathogenesis of intracranial aneurysms, their rupture, subarachnoid hemorrhage and neurologic complications. Proinflammatory cytokine level in blood and cerebrospinal fluid (CSF) is an indicator of inflammatory response. Cytokines contribute to secondary brain injury and can worsen the outcome of the treatment. Lidocaine is local anesthetic that can be applied in neurosurgery as regional anesthesia of the scalp and as topical anesthesia of the throat before direct laryngoscopy and endotracheal intubation. Besides analgesic, lidocaine has systemic anti-inflammatory and neuroprotective effect.Primary aim of this trial is to determine the influence of local anesthesia with lidocaine on the perioperative levels of pro-inflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α in plasma and CSF in cerebral aneurysm patients., Methods: We will conduct prospective randomized clinical trial among patients undergoing craniotomy and cerebral aneurysm clipping surgery in general anesthesia. Patients included in the trial will be randomly assigned to the lidocaine group (Group L) or to the control group (Group C). Patients in Group L, following general anesthesia induction, will receive topical anesthesia of the throat before endotracheal intubation and also regional anesthesia of the scalp before Mayfield frame placement, both done with lidocaine. Patients in Group C will have general anesthesia only without any lidocaine administration. The primary outcomes are concentrations of cytokines interleukin-1β, interleukin-6 and tumor necrosis factor-α in plasma and CSF, measured at specific timepoints perioperatively. Secondary outcome is incidence of major neurological and infectious complications, as well as treatment outcome in both groups., Discussion: Results of the trial could provide insight into influence of lidocaine on local and systemic inflammatory response in cerebrovascular surgery, and might improve future anesthesia practice and treatment outcome. TRIAL IS REGISTERED AT CLINICALTRIALS.GOV:: NCT03823482.