Amplifying hepatic L-aspartate levels suppresses CCl4-induced liver fibrosis by reversing glucocorticoid receptor ß-mediated mitochondrial malfunction.

Liver fibrosis is a determinant-stage process of many chronic liver diseases and affected over 7.9 billion populations worldwide with increasing demands of ideal therapeutic agents. Discovery of active molecules with anti-hepatic fibrosis efficacies presents the most attacking filed. Here, we revealed that hepatic L-aspartate levels were decreased in CCl4-induced fibrotic mice. Instead, supplementation of L-aspartate orally alleviated typical manifestations of liver injury and fibrosis. These therapeutic efficacies were alongside improvements of mitochondrial adaptive oxidation. Notably, treatment with L-aspartate rebalanced hepatic cholesterol-steroid metabolism and reduced the levels of liver-impairing metabolites, including corticosterone (CORT). Mechanistically, L-aspartate treatment efficiently reversed CORT-mediated glucocorticoid receptor ß (GRß) signaling activation and subsequent transcriptional suppression of the mitochondrial genome by directly binding to the mitochondrial genome. Knockout of GRß ameliorated corticosterone-mediated mitochondrial dysfunction and hepatocyte damage which also weakened the improvements of L-aspartate in suppressing GRß signaling. These data suggest that L-aspartate ameliorates hepatic fibrosis by suppressing GRß signaling via rebalancing cholesterol-steroid metabolism, would be an ideal candidate for clinical liver fibrosis treatment.

Ovarian Sex Cord Stromal Tumor in a Free-Ranging Brown Bear (Ursus arctos).

Reports on neoplasms in bears are scarce, especially concerning ovarian tumors. A large primary ovarian neoplasm with multiple metastasis was found during the necropsy of a 14-year-old free-ranging Eurasian brown bear (Ursus arctos) from Northwestern Spain. Histopathology and immunohistochemistry allowed for the diagnosis of a sex cord stromal tumor. This is a complex group of neoplasms which differ in the predominant cell morphology and immunohistochemical features. The microscopic examination revealed two types of cells, one with eosinophilic cytoplasm, intermingled with larger vacuolated cells rich in lipids. The evaluation of the immunoreactivity to different markers, frequently used in the characterization of gonadal tumors (INHA, inhibin-alpha; PLAP, placental alkaline phosphatase; Ki-67; α-SMA, actin alpha-smooth muscle) and inflammation patterns (IBA1, ionized calcium-binding adapter molecule for macrophages; CD3 for T lymphocytes; CD20 for B lymphocytes), displayed significant INHA positive immunostaining of neoplastic cells, as well as inflammatory cell infiltration, mainly composed of macrophages and B lymphocytes. These findings were consistent with a malignant ovarian steroid cell tumor, not otherwise specified. The present study characterizes an unusual type of neoplasm, and also represents the first report of an ovarian sex cord stromal tumor in Ursidae.

Glucocorticoid Receptors Orchestrate a Convergence of Host and Cellular Stress Signals in Triple Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks expression of the nuclear steroid receptors that bind estrogens (ER) and progestogens (PRs) and does not exhibit HER2 (Human epidermal growth factor 2) receptor overexpression. Even in the face of initially effective chemotherapies, TNBC patients often relapse. One primary cause for therapy-resistant tumor progression is the activation of cellular stress signaling pathways. The glucocorticoid receptor (GR), a corticosteroid-activated transcription factor most closely related to PR, is a mediator of both endocrine/host stress and local tumor microenvironment (TME)-derived and cellular stress responses. Interestingly, GR expression is associated with a good prognosis in ER+ breast cancer but predicts poor prognosis in TNBC. Classically, GR's transcriptional activity is regulated by circulating glucocorticoids. Additionally, GR is regulated by ligand-independent signaling events. Notably, the stress-activated protein kinase, p38 MAP kinase, phosphorylates GR at serine 134 (Ser134) in response to TME-derived growth factors and cytokines, including HGF and TGFß1. Phospho-Ser134-GR (p-Ser134-GR) associates with cytoplasmic and nuclear signaling molecules, including 14-3-3ζ, aryl hydrocarbon receptors (AhR), and hypoxia-inducible factors (HIFs). Phospho-GR/HIF-containing transcriptional complexes upregulate gene sets whose protein products include the components of inducible oncogenic signaling pathways (PTK6) that further promote cancer cell survival, chemoresistance, altered metabolism, and migratory/invasive behavior in TNBC. Recent studies have implicated liganded p-Ser134-GR (p-GR) in dexamethasone-mediated upregulation of genes related to TNBC cell motility and dysregulated metabolism. Herein, we review the tumor-promoting roles of GR and discuss how both ligand-dependent and ligand-independent/stress signaling-driven inputs to p-GR converge to orchestrate metastatic TNBC progression.

Enhancing contrast distribution with the far lateral approach in lumbar transforaminal epidural steroid injections: A retrospective analysis.

BACKGROUND: Herniated intervertebral disc (HIVD) with radiculopathy is a common degenerative spine disorder. Transforaminal epidural steroid injection (TFESI) is one of the pain relief treatments for lumbar radiculopathy recommended by evidence-based guidelines. Adequate contrast distribution is correlated with better pain control, but the best approach has not been confirmed yet. AIM: To confirm the distribution of contrast medium injected with a new approach of TFESI, that is, far lateral lateral recess approach (FLLR-TFESI). METHODS: Patients receiving TFESI due to HIVD with radiculopathy between 2010 January and 2020 August were retrospectively enrolled. While the FLLR-TFESI was taken as the experimental group, the conventional approach was viewed as the control group. The baseline characteristics, the pattern of contrast enhancement under fluoroscopic guidance, and the complications of these patients were collected and analyzed. RESULTS: A total of 380 patients were analyzed (143 in control group and 237 in experimental group). The two groups were balanced in most baseline characteristics, except disc extrusion (p = 0.01) and scoliosis (p = 0.04). The FLLR-TFESI have a better contrast distribution (p < 0.01), even after adjustment (p < 0.001). No intrathecal injection was noted, but higher rate of intra-disc injection was noted in FLLR-TFESI group (10% vs. 3%, p = 0.008). CONCLUSION: The FLLR-TFESI has a superior contrast enhancement and distribution in comparison to conventional approach. Prospective study to confirm the study result as well as the clinical benefits is suggested in the future.

Cancer to Cataracts: The Mechanistic Impact of Aldo-Keto Reductases in Chronic Diseases.

Aldo-keto reductases (AKRs) are a superfamily of promiscuous enzymes that have been chiseled by evolution to act as catalysts for numerous regulatory pathways in humans. However, they have not lost their promiscuity in the process, essentially making them a double-edged sword. The superfamily is involved in multiple metabolic pathways and are linked to chronic diseases such as cataracts, diabetes, and various cancers. Unlike other detoxifying enzymes such as cytochrome P450s (CYP450s), short-chain dehydrogenases (SDRs), and medium-chain dehydrogenases (MDRs), that participate in essential pathways, AKRs are more widely distributed and have members with interchangeable functions. Moreover, their promiscuity is ubiquitous across all species and participates in the resistance of pathogenic microbes. Moreover, the introduction of synthetic substrates, such as synthetic molecules and processed foods, results in unwanted "toxification" due to enzyme promiscuity, leading to chronic diseases.

Positive Myelin Oligodendrocyte Glycoprotein Antibodies in Isolated Optic Neuritis in a 14-Year-Old Child.

Optic neuritis (ON) is a rare condition in the pediatric age group. Patients with optic neuritis can manifest with a wide range of drops in vision, ranging from mild loss to complete loss of vision. Knowing the cause of optic neuritis is an important point that will affect management and prognosis. Anti-myelin oligodendrocyte glycoprotein (anti-MOG) antibody is an autoantibody that causes demyelination of the central nervous system (CNS). Treatment with a high dose of IV steroids followed by oral steroids is the best regimen that shows a favorable vision outcome. We aim to report this case of isolated optic neuritis with a positive anti-myelin oligodendrocyte glycoprotein antibody to highlight the prognosis of myelin oligodendrocyte glycoprotein disease with isolated optic neuritis and how early diagnosis and treatment can affect the visual outcome.

Chitosan-based crosslinking for controlled topical drug release in rhinosinusitis.

KEY POINTS: Chitosan is a promising drug delivery vector for therapeutics owing to its biocompatibility. Once crosslinked with chitosan, prolonged drug release was noted regardless of hydrophilicity. Hydrophilic drugs may require different strategies to obtain a sustained release profile.

Sex- and age-specific reference intervals of 16 steroid metabolites quantified simultaneously by LC-MS/MS in sera from 2458 healthy subjects aged 0 to 77 years.

BACKGROUND: Reference intervals covering the whole life span for all the metabolites in the steroid hormone biosynthesis quantified by sensitive and robust analytical methods are sparse or not existing. OBJECTIVE: To develop a state-of-the-art LC-MS/MS method for simultaneous quantification of multiple steroid metabolites and to establish detailed sex- and age-specific reference intervals for 16 steroid metabolites. MATERIALS AND METHOD: An isotope diluted LC-MS/MS method was developed for simultaneous quantitation of 16 steroid hormones. Serum samples from cross-sectional cohorts of healthy infants, children, adolescents, and adults aged 0.17 months to 77 years (n = 2458) were analysed. RESULTS: With this novel, specific, and sensitive LC-MS/MS method, it was possible to quantify progesterone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate, androstenedione, testosterone, dihydrotestosterone, 11-deoxycorticosterone, corticosterone, 11-deoxycortisol, cortisol, and cortisone in ≥90 % of the samples, while estrone sulfate, aldosterone and dehydroepiandrosterone were quantified in 77 %, 75 % and 60 % of the samples, respectively. 21-deoxycortisol was only detectable in 2.5 % of samples from healthy subjects. Sex- and age-dependent fluctuations observed in minipuberty, puberty and adulthood including the menopausal transition were modelled. This enabled us to establish valid reference intervals from birth to late adult life for both males and females. CONCLUSION: Detailed sex- and age-specific reference intervals of multiple, simultaneously quantified steroid metabolites by a novel and specific LC-MS/MS method provides a valuable tool for clinical practice and for future research.

Impact of steroid biosynthesis on the aerobic adaptation of eukaryotes.

Steroids are indispensable components of the eukaryotic cellular membrane and the acquisition of steroid biosynthesis was a key factor that enabled the evolution of eukaryotes. The polycyclic carbon structures of steroids can be preserved in sedimentary rocks as chemical fossils for billions of years and thus provide invaluable clues to trace eukaryotic evolution from the distant past. Steroid biosynthesis consists of (1) the production of protosteroids and (2) the subsequent modifications toward "modern-type" steroids such as cholesterol and stigmasterol. While protosteroid biosynthesis requires only two genes for the cyclization of squalene, complete modification of protosteroids involves ~10 additional genes. Eukaryotes universally possess at least some of those additional genes and thus produce modern-type steroids as major final products. The geological biomarker records suggest a prolonged period of solely protosteroid production in the mid-Proterozoic before the advent of modern-type steroids in the Neoproterozoic. It has been proposed that mid-Proterozoic protosteroids were produced by hypothetical stem-group eukaryotes that presumably possessed genes only for protosteroid production, even though in modern environments protosteroid production as a final product is found exclusively in bacteria. The host identity of mid-Proterozoic steroid producers is crucial for understanding the early evolution of eukaryotes. In this perspective, we discuss how geological biomarker data and genetic data complement each other and potentially provide a more coherent scenario for the evolution of steroids and associated early eukaryotes. We further discuss the potential impacts that steroids had on the evolution of aerobic metabolism in eukaryotes, which may have been an important factor for the eventual ecological dominance of eukaryotes in many modern environments.

Rituximab versus tacrolimus as corticosteroid-sparing therapy for children with steroid-dependent nephrotic syndrome: A systematic review and meta-analysis of randomized and nonrandomized controlled trials.

Objectives: Prolonged use of corticosteroids induced complicated course in children with steroid-dependent nephrotic syndrome (SDNS), and the use of tacrolimus, a first-line alternative calcineurin inhibitor (CNI) agent was related to some unwanted adverse effects. Rituximab, a second alternative treatment has been proven to reliably reduce the number of relapses within 12 months with minimal adverse effects. Materials and Methods: Our review follows Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. All the databases were derived from MEDLINE, Proquest, EBSCOhost, Wiley, and Google Scholar within the past 11 years. The risk of bias was evaluated using the Revised Cochrane Risk of Bias Tool for Randomized Trials (RoB 2) and Risk of Bias in Non-Randomized Studies of Interventions. Meta-analysis used Review Manager (version 5.4) with a random effect model to obtain a pooled mean difference (MD) and odds ratio with 95% confidence intervals (CIs). Results: Four studies were included based on our eligibility criteria, and only three were included in the quantitative analysis. Three studies had low and one study had a moderate risk of bias. Pooled data results indicated that Rituximab was superior to tacrolimus in reducing the number of patients with 1-2 relapses (MD = 0.44, [95% CI: 0.21-0.91]) and had higher eGFR values (MD = 6.67; [CI - 2.92-10.61]). However, Rituximab showed insignificant superiority compared to tacrolimus in reducing the number of patients with 3 relapses, sustained remission, cumulative steroid use, serum cholesterol, and serum albumin concentrations. Conclusion: Rituximab exhibits more advantages in treating SDNS compared to tacrolimus, although the treatment options are highly individualized. Both regimens must also be weighed against their potential side effects to achieve a better overall health status.

Combined use of intravitreal bevacizumab and oral steroid treatment in three diabetic papillopathy patients: a diagnostic and treatment challenge.

Diabetic papillopathy (DP), a form of optic disc edema, is characterized by decreased visual acuity and mild to severe visual field defects. While there is no consensus about treatment, some publications report that intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection may be beneficial. To our knowledge, however, no research reports on the effects of combining anti-VEGF injection and oral steroids in DP treatment. In this case report we present three DP cases that showed rapid improvement following therapy with intravitreal bevacizumab and oral steroids. Optic disc edemas were significantly decreased, and visual acuities were markedly increased in the first week of treatment. This report suggests that combined use of these therapies may be safely used in patients diagnosed with DP.

Steroid metabolism and hormonal dynamics in normal and malignant ovaries.

The ovaries are key steroid hormone production sites in post-pubertal females. However, current research on steroidogenic enzymes, endogenous hormone concentrations and their effects on healthy ovarian function and malignant development is limited. Here, we discuss the importance of steroid enzymes in normal and malignant ovaries, alongside hormone concentrations, receptor expression and action. Key enzymes include STS, 3ß-HSD2, HSD17B1, ARK1C3, and aromatase, which influence ovarian steroidal action. Both androgen and oestrogen action, via their facilitating enzyme, drives ovarian follicle activation, development and maturation in healthy ovarian tissue. In ovarian cancer, some data suggest STS and oestrogen receptor α may be linked to aggressive forms, while various oestrogen-responsive factors may be involved in ovarian cancer metastasis. In contrast, androgen receptor expression and action vary across ovarian cancer subtypes. For future studies investigating steroidogenesis and steroidal activity in ovarian cancer, it is necessary to differentiate between disease subtypes for a comprehensive understanding.

Conditional Inhibition of Eip75B Eliminates the Effects of Mating and Mifepristone on Lifespan in Female Drosophila.

Mating in female Drosophila melanogaster causes midgut hypertrophy and reduced lifespan, and these effects are blocked by the drug mifepristone. Eip75B is a transcription factor previously reported to have pleiotropic effects on Drosophila lifespan. Because Eip75B null mutations are lethal, conditional systems and/or partial knock-down are needed to study Eip75B effects in adults. Previous studies showed that Eip75B is required for adult midgut cell proliferation in response to mating. To test the possible role of Eip75B in mediating the lifespan effects of mating and mifepristone, a tripartite FLP-recombinase-based conditional system was employed that provides controls for genetic background. Expression of a Hsp70-FLP transgene was induced in third instar larvae by a brief heat pulse. The FLP recombinase catalyzed the recombination and activation of an Actin5C-GAL4 transgene. The GAL4 transcription factor in turn activated expression of a UAS-Eip75B-RNAi transgene. Inhibition of Eip75B activity was confirmed by loss of midgut hypertrophy upon mating, and the lifespan effects of both mating and mifepristone were eliminated. In addition, the negative effects of mifepristone on egg production were eliminated. The data indicate that Eip75B mediates the effects of mating and mifepristone on female midgut hypertrophy, egg production, and lifespan.

Ultrasonographic evaluation of changes in the joint before and after intra-articular injection in children with juvenile idiopathic arthritis.

OBJECTIVE: The aim of this study is to ultrasonographically (US) evaluate the course of the knee joint in oligoarticular juvenile idiopathic arthritis (JIA) patients who received intra-articular steroid (IAS) application to the knee joint. METHODS: 237 knee joints of 175 patients with oligoarticular JIA were evaluated retrospectively. The patients were divided into two groups: those who received only IAS therapy and those who were methotrexate to IAS therapy. Synovial fluid grade changes, synovial proliferation in B mode examination and power Doppler (PD) changes were evaluated with musculoskeletal ultrasonography (MSUS) separately for each joint before the treatment and at the 2nd, 6th and 12th weeks of the treatment. RESULTS: The percentages of regression in synovial fluid grade at the second, sixth, and 12th weeks were respectively 73.4%, 88.6%, and 89.0% (n=174, 210, 211, respectively). Meanwhile, the percentages of regression in PD grade were 69.2%, 82.7%, and 84.0% (n=164, 196, 199, respectively). At the second, sixth and 12th weeks, the percentage of those with synovial fluid grade 0 was 24.1%, 54.9%, 73.4%, respectively (n=57, 130, 174, respectively), while the percentage of those with PD grade 0 was 39.7%, 67.9%, 80.6%, respectively (n=94,161,191, respectively). The percentage of those without synovial proliferation in the second, sixth and 12th weeks was found to be 26.2%, 54.9%, 73.8% respectively (n=62, 130, 175, respectively). The mean time to regression of synovial fluid, synovial proliferation, and PD in the only IAS group was significantly short. The percentage of synovitis regression was higher in the only IAS group at all weeks. This difference was especially more pronounced in the early period. When the 12th-week results were evaluated, there was no difference between the two groups. CONCLUSION: This study highlights the utility of MSUS in evaluating the early results of IAS therapy applied to the knee joint in oligoarticular JIA patients.

Mid-term survivorship and clinical results of cementless total hip arthroplasty for steroid-induced avascular necrosis.

OBJECTIVE: The purpose of the present study was to evaluate the mid-term implant survivorship, modes of failure, radiographic results, and clinical outcomes of current cementless total hip arthroplasty (THA) treatment designs for steroid-induced avascular necrosis (AVN). METHODS: A time span of 5 years between January 2012 and November 2017 was scanned to accommodate 5 years of follow-up and a total of 15 patients (18 hips), who had undergone implantation of ultra-high molecular weight polyethylene (UHMWPE) and newly designed other head and liner components, were included in the study. Only patients operated for steroid-induced AVN were included in the study. Patients with alcohol-induced, idiopathic, and traumatic AVN were excluded from the study. The primary outcomes were the assessments of Harris Hip Score (HHS) and the presence of loosening, osteolysis, polyethylene wear or a reoperation (with or without revision of components). The fixation of cementless femoral components was assessed according to Engh criteria. RESULTS: The study group consisted of 18 hips from 15 patients. The mean age was 47.6±8.1 (29-55) years. A cementless femoral stem and acetabular cup were used for all patients. Septic loosening was detected in all components of one patient (5.6%). The mean HHS score was 83.3±7.2 (60-92) for all patients. Of the 18 hips, 83% (15 hips), 5.6% (1 hip), 5.6% (1 hip), and 5.6% (1 hip) had good, poor, fair, and excellent HHS scores. Ceramic or polyethylene liner wear was not detected in any of the patients. The Engh Grading Scale revealed a "bone ingrowth" in 16 (89%) hips, "suspected in-growth" in 1 (5.6%) hip and "suboptimum but stable" femoral fixation in a patient with septic loosening (5.6%) just before revision surgery. There was no significant correlation between femoral stem design and Engh score (p=0.842). CONCLUSION: Modern total hip arthroplasty systems, including ceramic on ceramic or ceramic on polyethylene headliner options with cementless femoral stem, offer promising mid-term survivorship and positive clinical outcomes for steroid-induced AVN treatment. However, studies including long-term follow-ups with larger sample size are needed to obtain more precise data.

The effect of hydrocortisone versus hydrocortisone plus fludrocortisone on duration of shock: A propensity score-weighted analysis.

Background: The 2021 Surviving Sepsis Campaign Guidelines recommend the use of hydrocortisone in patients who remain hemodynamically unstable despite adequate fluid resuscitation and vasopressor therapy. Fludrocortisone has been used concomitantly with hydrocortisone in some studies without a clearly defined role or known clinical benefit. The purpose of this study was to assess the impact of fludrocortisone added to hydrocortisone on shock-free days for septic shock. Methods: A single-center, retrospective propensity score-weighted study was conducted to compare hydrocortisone versus hydrocortisone plus fludrocortisone for septic shock. Adults admitted to the medical intensive care unit (ICU) from 2015 to 2020 were included in the study. All patients received ≥200 mg/day hydrocortisone for at least 24 h ± fludrocortisone initiated within 72 h of vasopressors. The primary outcome was shock-free days by day 14. The secondary outcomes included duration of shock, change in Sequential Organ Failure Assessment (SOFA) score, hospital and ICU length of stay, and all-cause inhospital mortality. Results: A total of 228 patients met inclusion criteria with 212 patients retained after propensity score weighting. There was no difference between groups in 14-day shock-free days (6.3 vs. 6.1 days; P = 0.781). Furthermore, no significant differences were observed for the secondary outcomes of ICU/hospital length of stay, duration of shock, change in SOFA score, and all-cause inhospital mortality. Conclusion: The addition of fludrocortisone to hydrocortisone in septic shock did not increase shock-free days by day 14. These results suggest that the use of hydrocortisone alone may be an adequate adjunctive therapy in septic shock. A prospective randomized controlled trial is needed to confirm results.

Case Report of Minimal Change Disease in the Adult Population.

Minimal change disease (MCD), typically linked with pediatric nephrotic syndrome, presents challenges in early identification and diagnosis in adult populations. This case report emphasizes the importance of tailored diagnostic and treatment approaches for adults with MCD. Our patient presented with fatigue, shortness of breath, and confusion, along with other symptoms leading to a renal biopsy which confirmed MCD. This highlights the diagnostic significance of kidney biopsy in adults. While steroids remain the standard treatment, challenges such as resistance and side effects lead to the consideration of alternatives like tacrolimus. There are nuanced differences between adult and pediatric MCD presentations, for which our study calls for increased awareness among physicians. Steroids are considered a first-line treatment for MCD, but prolonged use of steroids has significantly increased risk and alternative therapies should be considered. This study presents an example of MCD in adult populations, urging ongoing research for enhanced understanding and tailored management strategies. It emphasizes the pivotal role of physician awareness, alternative treatments, and continued investigation to improve outcomes for adults with MCD.

Burkholderia cepacia in cystic fibrosis children and adolescents: overall survival and immune alterations.

Background: In current literature there are only scarce data on the host inflammatory response during Burkholderia cepacia complex (Bcc) persistence. The primary objective of the present research was to carry out cross-sectional analyses of biomarkers and evaluate disease progression in cystic fibrosis (CF) patients with chronic Bcc infection and pathogen-free ones. The secondary aim was to assess prospectively overall survival of the study participants during up to 8 years of follow-up. Methods: The study included 116 paediatric patients with CF; 47 CF patients were chronically infected with Bcc, and 69 individuals were Bcc free. Plasma and sputum biomarkers (neutrophil elastase, MMP-8, MMP-9, MMP-12, IL-2, IL-4, IL-6, IL-8, IL-10, IL-18, IL-22, IL-23, IL-17, IFN-γ, TGFß1, TNF-α) were analysed using commercially available kits. Besides, inhibitory effect of dexamethasone on proliferative response of PHA-stimulated peripheral blood lymphocytes had been assessed. Results: Bcc infected patients did not differ from Bcc free ones in demographic and clinical parameters, but demonstrated an increased rate of glucose metabolism disturbances and survival disadvantage during prolong follow-up period. Biomarkers analyses revealed elevated TNF-α and reduced IL-17F levels in sputum samples of Bcc infected patients. These patients also demonstrated improvement of peripheral blood lymphocyte sensitivity to steroid treatment and reduction in plasma pro-inflammatory (IL-17F and IL-18) and anti-inflammatory (TGFß1 and IL-10) cytokine concentrations. Conclusions: Reduction in IL-17F levels may have several important consequences including increase in steroid sensitivity and glycemic control disturbances. Further investigations are needed to clarify the role of IL-17 cytokines in CF complication development. Low plasma TGFß1 and IL-10 levels in Bcc infected group may be a sign of subverted activity of regulatory T cells. Such immune alterations may be one of the factors contributing to the development of the cepacia syndrome.

Difficulties in the Diagnostics and Treatment of Hashimoto's Encephalopathy-A Systematic and Critical Review.

Hashimoto's encephalopathy (HE) has been a poorly understood disease. It has been described in all age group, yet, there is no specific HE marker. Additionally, the treatment data in the available studies are frequently divergent and contradictory. Therefore, the aim of our systematic and critical review is to evaluate the diagnosis and treatment of HE in view of the latest findings. The databases browsed comprised PubMed, Scopus, and Google Scholar as well as Cochrane Library, and the search strategy included controlled vocabulary and keywords. A total of 2443 manuscripts were found, published since the beginning of HE research until February 2024. In order to determine validity of the data collected from studies, bias assessment was performed using RoB 2 tool. Ultimately, six studies were included in our study. HE should be considered in the differential diagnosis in patients with psychiatric and neurological symptoms. According to our findings, negative thyroid peroxidase antibodies (anti-TPOs) may represent a valuable parameter in ruling out HE. Nonetheless, this result cannot be used to confirm HE. Furthermore, the proposed anti NH2-terminal-α-enolase (anti-NAE) is non-specific for HE. The effectiveness of glucocorticoid therapy is 60.94%, although relapse occurs in 31.67% of patients following the treatment. Our review emphasizes the significance of conducting further large-scale research and the need to take into account the potential genetic factor.

Unraveling the Clinical Features and Outcomes of IgG4-Related Ophthalmic Disease.

Background/Objectives: IgG4-related ophthalmic disease (IgG4-ROD), characterized by lymphoplasmacytic infiltration, fibrosis, and elevated IgG4 levels, presents diagnostic challenges while offering insights into immune-mediated inflammatory disorders. The aim of this study was to comprehensively examine the clinical features and outcomes of IgG4-ROD. Materials and Methods: A retrospective study was conducted on 33 patients diagnosed with IgG4-ROD, fulfilling the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria. The demographic characteristics of the IgG4-ROD patients were compared with those of 37 patients diagnosed with IgG4-related disease (IgG4-RD) in departments other than ophthalmology (IgG4-nonROD) at the same hospital during the same period. The patients diagnosed with IgG4-ROD were initially treated with glucocorticosteroid (GCS) monotherapy, GCS combined with steroid-sparing agents (SSAs; mycophenolate mofetil, azathioprine, hydroxychloroquine), biologic agent (rituximab) monotherapy, or watchful waiting. The primary outcome was the assessed treatment response at 6 months, and the secondary outcome was the evaluation of recurrence at 1 year after initial treatment. A response was evaluated as the absence of ocular signs and symptoms, either clinically or radiologically. Results: Eyelid swelling (17 patients, 51.5%) was the most common symptom, and lacrimal gland (17 patients, 51.5%) was the most frequent site of involvement. The response rate for GCS monotherapy was 33.3% (3 out of 9 patients), while the response rate for GCS combined with SSA was 60.0% (9 out of 15 patients). The lacrimal gland group demonstrated a significantly higher treatment response compared to the non-lacrimal gland group (66.7% vs. 20.0%, p = 0.013), and the combination of GCS and SSA resulted in a significantly higher treatment response than the GCS monotherapy (77.8% vs. 33.3%, p = 0.045). The group including hydroxychloroquine (HCQ), which comprised 5 out of 33 patients (15.2%), showed no recurrence at 1 year. Conclusions: The combination therapy of GCS and SSA for IgG4-ROD can be considered an effective treatment approach and HCQ could be considered as a potential adjunctive therapy for IgG4-ROD.