Rethinking Aspergillosis in the Era of Microbiota and Mycobiota.

Aspergillosis encompasses a wide range of clinical conditions based on the interaction between Aspergillus and the host. It ranges from colonization to invasive aspergillosis. The human lung provides an entry door for Aspergillus. Aspergillus has virulence characteristics such as conidia, rapid growth at body temperature, and the production of specific proteins, carbohydrates, and secondary metabolites that allow A. fumigatus to infiltrate the lung's alveoli and cause invasive aspergillosis. Alveolar epithelial cells play an important role in both fungus clearance and immune cell recruitment via cytokine release. Although the innate immune system quickly clears conidia in immunocompetent hosts, A. fumigatus has evolved multiple virulence factors in order to escape immune response such as ROS detoxifying enzymes, the rodlet layer, DHN-melanin and toxins. Bacterial co-infections or interactions can alter the immune response, impact Aspergillus growth and virulence, enhance biofilm formation, confound diagnosis, and reduce treatment efficacy. The gut microbiome's makeup influences pulmonary immune responses generated by A. fumigatus infection and vice versa. The real-time PCR for Aspergillus DNA detection might be a particularly useful tool to diagnose pulmonary aspergillosis. Metagenomics analyses allow quick and easy detection and identification of a great variety of fungi in different clinical samples, although optimization is still required particularly for the use of NGS techniques. This review will analyze the current state of aspergillosis in light of recent discoveries in the microbiota and mycobiota.

Successful pregnancies in a patient with Takayasu arteritis and antiphospholipid syndrome, maintained on infliximab corticosteroid-free regimen: case-based review.

Takayasu arteritis (TA) is a large vessel vasculitis affecting predominantly females below the age of 40. Patients with TA seem to be at increased risk for adverse pregnancy outcomes, resulting in mother or child complications. Although few studies analyzed the presence of antiphospholipid antibodies (APLA) in TA patients, an association between antiphospholipid syndrome (APS) and TA is rarely reported in the literature, mainly in the form of case reports. In fact, very few data regarding pregnancy outcomes in patients with TA and APS are available. An active form of Crohn's disease (CD) might be another risk factor strongly affecting the fertility rate. Here, we would like to present a 33-year-old woman with TA, double-positive APS and Crohn's disease (CD). The report is followed by the literature review of the association of APLA and/or APS with TA, focusing on analyzing the pregnancy outcomes. To our knowledge, this is the first case describing two successful, naturally occurring pregnancies, in a patient suffering from TA, APS and CD, and maintained on infliximab, azathioprine, and a corticosteroid-free regimen.

Epstein-Barr Virus Reactivation as a New Predictor of Achieving Remission or Lupus Low Disease Activity State in Patients with Systemic Lupus Erythematosus with Cutaneous Involvement.

Although Epstein-Barr virus (EBV) reactivation has long been associated with the pathogenesis of systemic lupus erythematosus (SLE), many aspects of this relationship remain unclear. Our objective was to investigate the association between EBV reactivation and the achievement of SLE remission and lupus low disease activity state (LLDAS) over a six-month period. Clinical, laboratory, and virological tests (anti-EBV antibodies and EBV DNA) were performed among 51 patients with the active form of SLE on two occasions six months apart. SLE remission and LLDAS achievement were assessed at the end of the follow-up period. Active EBV infection was detected in 45% of active SLE patients at baseline, and 77% transitioned to latent EBV infection at six months (p < 0.001). Multivariate regression revealed a higher titer of anti-EA(D) IgM-Abs and the presence of anti-EA(D) IgM-Abs as independent predictors of remission and LLDAS in SLE patients with mucocutaneous manifestations (p = 0.042) and rash only (p = 0.023), respectively. Since a higher C3 level was an independent predictor of transition to latent EBV infection (p = 0.027), the estimated cut-off value that could identify active SLE patients who will transition to latent EBV infection after six months was ≥0.780 g/L with a sensitivity of 70.6% and a specificity of 75.0% (AUC = 0.756, p = 0.003). EBV reactivation is common in patients with active SLE, and most of them transition to latent EBV infection after six months. Achieving remission and LLDAS in SLE patients with mucocutaneous manifestations can be predicted by a higher titer, whereas in SLE patients who have only a rash, the presence of anti-EA (D) IgM-Abs was a predictor of remission and LLDAS.

ST2 and the alteration of cobalt, sodium, potassium and calcium concentration in acute inflammation.

INTRODUCTION: ST2 is the receptor for interleukin (IL)-33, the last discovered member of the IL-1 cytokine family. Acute inflammation is an early response of vascularized tissue to injury, in which alteration of micro- and macro-elements occurs. This study aimed to examine the alteration of cobalt, sodium, potassium, and calcium concentration at the site of acute inflammation and the role of ST2 in these alterations. MATERIAL AND METHODS: Wild-type (WT) and ST2 knockout (ST2-/-) mice were divided into groups: WT control group (WT-C), ST2 knockout control group (KO-C), WT inflammatory group (WT-I), and ST2 knockout inflammatory group (KO-I). We induced acute inflammation by intramuscular injection of turpentine oil or saline in the case of the control group. After 12 h, we anesthetized mice and collected treated tissues for histopathological analysis and determination of cobalt, sodium, potassium, and calcium concentration by atomic absorption spectrometer. RESULTS: Histopathological analysis showed the inflammatory infiltrate and cell necrosis in the treated tissue in WT-I and KO-I. The concentration of sodium was significantly lower in WT-I than in WT-C. The concentration of potassium and cobalt was significantly lower in WT-I and KO-I when compared to WT-C and KO-C, respectively. However, the concentration of potassium and cobalt in the tissue was significantly lower in WT-I than in KO-I. The concentration of calcium in the tissue did not significantly differ between groups. CONCLUSION: We reported, to our knowledge for the first time, that ST2 is involved in decreasing sodium, potassium, and cobalt concentration at the site of acute inflammation.

Mortality predictors of patients suffering of acute pancreatitis and development of intraabdominal hypertension

Background/aim: Intraabdominal hypertension (IAH) occurs frequently in patients with acute pancreatitis and adds to their morbidity and mortality. The main aim of the study was to identify the determination of the predictive factors connected to IAH that influence the evolution of acute pancreatitis. Materials and methods: The prospective cohort study was conducted on 100 patients who had acute pancreatitis. According to obtained intraabdominal pressure (IAP) values, the patients were divided into two groups: one group (n = 40) with normal IAP values and the other (IAH group, n = 60) with increased IAP values. Deceased patients were specially analyzed within the IAH group in order to determine mortality predictors. Results: Statistical significance of IAP (P = 0.048), lactates (P = 0.048), peak pressure (P = 0.043), abdominal perfusion pressure (P = 0.05), and mean arterial pressure (P = 0.041) was greater for deceased than for surviving patients in the IAH group. High mortality appears for patients younger than 65 years old, with lactate level higher than 3.22 mmol/L and filtration gradient (GF) lower than 67 mmHg. Conclusion: Age, lactates, GF, and APACHE II score are determined as mortality predictors for patients suffering from acute pancreatitis who developed IAH. The mortality rate is higher when the level of GF is decreasing and the level of lactate increasing.

Gal-3 regulates the capacity of dendritic cells to promote NKT-cell-induced liver injury.

Galectin-3 (Gal-3), an endogenous lectin, exhibits pro- and anti-inflammatory effects in various disease conditions. In order to explore the role of Gal-3 in NKT-cell-dependent pathology, we induced hepatitis in C57BL/6 WT and Gal-3-deficient mice by using specific ligand for NKT cells: α-galactosylceramide, glycolipid Ag presented by CD1d. The injection of α-galactosylceramide significantly enhanced expression of Gal-3 in liver NKT and dendritic cells (DCs). Genetic deletion or selective inhibition of Gal-3 (induced by Gal-3-inhibitor TD139) abrogated the susceptibility to NKT-cell-dependent hepatitis. Blood levels of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-12) and their production by liver DCs and NKT cells were also downregulated. Genetic deletion or selective inhibition of Gal-3 alleviated influx of inflammatory CD11c(+) CD11b(+) DCs in the liver and favored tolerogenic phenotype and IL-10 production of liver NKT and DCs. Deletion of Gal-3 attenuated the capacity of DCs to support liver damage in the passive transfer experiments and to produce pro-inflammatory cytokines in vitro. Gal-3-deficient DCs failed to optimally stimulate production of pro-inflammatory cytokines in NKT cells, in vitro and in vivo. In conclusion, Gal-3 regulates the capacity of DCs to support NKT-cell-mediated liver injury, playing an important pro-inflammatory role in acute liver injury.

Metformin aggravates immune-mediated liver injury in mice.

Hepatotoxicity of the antidiabetic drug metformin has been reported, but the underlying mechanisms remain unclear. We here investigated the effect of metformin in immune-mediated liver damage. While not hepatotoxic alone, metformin (200 mg/kg) aggravated concanavalin A (Con A, 12 mg/kg)-induced hepatitis, an experimental model of T cell-mediated liver injury, in both relatively resistant BALB/c and highly susceptible C57Bl/6 mice. Metformin + Con A-treated mice had elevated serum levels of pro-inflammatory cytokines TNF-α and IFN-γ, accompanied by a massive mononuclear cell infiltration in the liver. This was associated with the higher numbers of CD4(+) T cells producing TNF-α, IFN-γ and IL-17, CD4(+) T cells expressing chemokine receptor CXCR3 and activation marker CD27, CD4(+)CD62L(-)CCR7(-) and CD8(+)CD62L(-)CCR7(-) effector memory cells, IFN-γ producing NK cells, IL-4 and IL-17 producing NKT cells and IL-12 producing macrophages/dendritic cells. The percentage of CD4(+)CXCR3(+)Tbet(+)IL-10(+) and CD4(+)CD69(+)CD25(-) regulatory T cells was reduced. Metformin stimulated inducible nitric oxide synthase (iNOS) expression in the liver and spleen, and genetic deletion of iNOS attenuated the hepatotoxicity of metformin. Metformin increased the autophagic light chain 3 conversion and mRNA expression of important autophagy-inducing (beclin-1, Atg5 and GABARAP) and pro-apoptotic (p21, p27, Puma, Noxa, Bax, Bad, Bak1, Bim and Apaf1), but not anti-apoptotic molecules (Bcl-xL, survivin and XIAP), which correlated with the apoptotic caspase-3/PARP cleavage in the liver. The autophagy inhibitor chloroquine (20 mg/kg) prevented liver injury and apoptotic changes induced by metformin. Therefore, metformin aggravates immune-mediated hepatitis by promoting autophagy and activation of immune cells, affecting effector, as well as liver-specific regulatory T cells and iNOS expression.

Case report: Rapidly progressive neurocognitive disorder with a fatal outcome in a patient with PU.1 mutated agammaglobulinemia.

Introduction: PU.1-mutated agammaglobulinemia (PU.MA) represents a recently described autosomal-dominant form of agammaglobulinemia caused by mutation of the SPI1 gene. This gene codes for PU.1 pioneer transcription factor important for the maturation of monocytes, B lymphocytes, and conventional dendritic cells. Only six cases with PU.MA, presenting with chronic sinopulmonary and systemic enteroviral infections, have been previously described. Accumulating literature evidence suggests a possible relationship between SPI1 mutation, microglial phagocytic dysfunction, and the development of Alzheimer's disease (AD). Case description: We present a Caucasian female patient born from a non-consanguineous marriage, who was diagnosed with agammaglobulinemia at the age of 15 years when the immunoglobulin replacement therapy was started. During the following seventeen years, she was treated for recurrent respiratory and intestinal infections. At the age of 33 years, the diagnosis of celiac-like disease was established. Five years later progressive cognitive deterioration, unstable gait, speech disturbances, and behavioral changes developed. Comprehensive microbiological investigations were negative, excluding possible infective etiology. Brain MRI, 18FDG-PET-CT, and neuropsychological testing were suggestive for a diagnosis of a frontal variant of AD. Clinical exome sequencing revealed the presence of a novel frameshift heterozygous variant c.441dup in exon 4 of the SPI1 gene. Despite intensive therapy, the patient passed away a few months after the onset of the first neurological symptoms. Conclusion: We describe the first case of PU.MA patient presenting with a rapidly progressive neurocognitive deterioration. The possible role of microglial dysfunction in patients with SPI1 mutation could explain their susceptibility to neurodegenerative diseases thus highlighting the importance of genetic testing in patients with inborn errors of immunity. Since PU.MA represents a newly described form of agammaglobulinemia, our case expands the spectrum of manifestations associated with SPI1 mutation.

Evaluation of Intra-Abdominal Hypertension Parameters in Patients with Acute Pancreatitis.

BACKGROUND: Patients with acute pancreatitis develop numerous complications and organ damage due to increased intra-abdominal pressure (IAP). These extrapancreatic complications determine the clinical outcome of the disease. MATERIALS AND METHODS: A total of 100 patients with acute pancreatitis were included in the prospective cohort study. Observed patients were divided into two groups according to their mean values of IAP (normal IAP values and elevated IAP values), which were compared with examined variables. Patients with intra-abdominal hypertension (IAH) were divided into four groups by IAP values, and those groups of patients were also compared with the examined variables. RESULTS: Differences between body mass index (BMI) (p = 0.001), lactates (p = 0.006), and the Sequential Organ Failure Assessment (SOFA) score (p = 0.001) were statistically significant within all examined IAH groups. Differences between the mean arterial pressure (MAP) (p = 0.012) and filtration gradient (FG) (p < 0.001) were statistically significant between the first and second IAH groups in relation to the fourth. Differences in diuresis per hour (p = 0.022) showed statistical significance in relation to the first and third groups of IAH patients. CONCLUSIONS: Changes in IAP values lead to changes in basic vital parameters MAP, APP, FG, diuresis per hour, and lactate levels in patients with acute pancreatitis. Early recognition of changes in the SOFA score accompanying an increase in the IAP value is essential.

Molecular diagnostics and inhibition of cross-reactive carbohydrate determinants in Hymenoptera venom allergy.

BACKGROUND: The composition of venom extracts, cross-reactive carbohydrate determinants (CCD) and the component-resolved diagnostics (CRD) are important fields of investigation. IgE-reactivity to CCD complicates the interpretation of IgE to Hymenoptera venoms, especially in patients with multiple-positivity. We analyzed the clinical importance of CRD and CCD-inhibition for selection of allergens for venom immunotherapy (VIT). METHODS: In 71 patients, we measured specific IgE (sIgE) to honeybee venom (HBV), wasp venom (WV), hornet venom (HV), CCD, and recombinant allergens: phospholipase A2 (rApi m 1), hyaluronidase (rApi m 2), icarapin (rApi m 10), antigen 5 (rVes v 5), and phospholipase A1 (Immunoblot). In 29/71 HBV/WV/HV/CCD-positive patients CCD-inhibition was performed. According to CRD and CCD-inhibition, we identified true sensitization and defined groups of multiple-positive patients who needed CCD-inhibition before starting VIT. RESULTS: sIgE-rApi m 1, sIgE-rApi m 2, and sIgE-rApi m 10 were detected in 65.7%, 68.4%, and 58%, respectively. In HBV allergic patients, CRD sensitivity was 86.8%. In WV allergic patients, sensitivity of sIgE-rVes v 5 was 94%. True multiple-sensitization was found in 44.8% of HBV/WV/HV/CCD-positive patients after CCD-inhibition. Patients with multiple venom- and CCD-positivity had more frequent severe allergic reactions (p < 0.001). CCD-inhibition was helpful in HBV/WV/HV/CCD-positive patients who were negative to all tested recombinant honeybee allergens. Persistence of HBV-positivity after CCD-inhibition requires CRD to other honeybee recombinant allergens. CONCLUSION: CRD, using a profile of five most important recombinant allergens and CCD, has a high sensitivity for the diagnosis of venom allergy, especially in patients positive to several venom extracts. CRD and CCD-inhibition are helpful to reveal the clinically relevant, true sensitization and improve the selection of venoms for long-lasting VIT.

Diagnosis of Chronic Pulmonary Aspergillosis: Clinical, Radiological or Laboratory?

Chronic pulmonary aspergillosis (CPA) is a chronic progressive lung disease associated with a poor prognosis and a 5-year mortality rate of approximately 40-50%. The disease is characterized by slowly progressive destruction of the lung parenchyma, in the form of multiple cavities, nodules, infiltrates or fibrosis. CPA can be challenging to diagnose due to its non-specific symptoms and similarities with other respiratory conditions combined with the poor awareness of the medical community about the disease. This can result in delayed treatment even for years and worsening of the patient's condition. Serological tests certainly play a significant role in diagnosing CPA but cannot be interpreted without radiological confirmation of CPA. Although many data are published on this hot topic, there is yet no single definitive test for diagnosing CPA, and a multidisciplinary approach which involves a combination of clinical picture, radiological findings, microbiological results and exclusion of other mimicking diseases, is essential for the accurate diagnosis of CPA.

Myositis-specific autoantibodies in a non-traveler, patient from a non-endemic country, with Plasmodium vivax malaria.

INTRODUCTION: Autoantibodies (AAb) are a hallmark of immune-mediated inflammatory diseases. Malaria is a parasitic disease caused by Plasmodium protozoa. Individuals with malaria may present with a wide range of symptoms. It is frequently linked to the development of different AAb. CASE DESCRIPTION: A 35-year-old male presented with repeated episodes of fever, malaise, myalgia, dark urine, and yellowish sclera. Initial diagnostic workup revealed severe Coombs-positive anemia, increased C-reactive protein, and procalcitonin, pathological liver tests, high concentration of serum IgE, IgG, IgM, IgA, positive antinuclear antibodies (ANA), and positive antineutrophil cytoplasmatic antibodies (ANCA). In addition, myositis-specific antibodies directed to polymiositis-scleroderma 75 protein (PmScl75), threonyl-tRNA synthetase (PL-7), alanyl-tRNA synthetase (PL-12), Mi-2 antigen (Mi-2), Ku DNA helicase complex (Ku), signal recognition particle (SRP), and antiaminoacyl tRNA synthetase (EJ) were detected. The patient was suspected of having systemic lupus erythematosus and sent to the Clinic of Allergy and Immunology for further evaluation and treatment. A peripheral blood film examined by the hematologist during an episode of fever revealed intra-erythrocytic parasitic forms of Plasmodium vivax (P. vivax). After being diagnosed with P. vivax malaria, he was transferred to the Clinic for Infective and Tropical Diseases. The therapy consisted of artesunate/mefloquine and prednisone led to a complete clinical recovery and autoantibodies gradually disappeared. CONCLUSIONS: Malaria would not normally be considered during the initial diagnostic workup in a non-traveler and a patient from a non-endemic country. However, a thorough parasitic evaluation in patients presenting with a broad range of autoantibodies might be of particular importance.

Large-Vessel Giant Cell Arteritis following COVID-19-What Can HLA Typing Reveal?

Giant cell arteritis (GCA) is an immune-mediated vasculitis that affects large arteries. It has been hypothesized that viruses may trigger inflammation within the vessel walls. Genetic studies on human leukocyte antigens (HLAs) have previously reported HLA-DRB1*04 as a susceptible allele for GCA and HLA-DRB1*15 as a protective allele for GCA. Here, we discuss the clinical presentation, laboratory findings, HLA class I and class II analysis results, and management of patients with extracranial large-vessel (LV) GCA, detected at least six weeks after recovery from COVID-19. This case series encompassed three patients with LV-GCA (two males and a female with an age range of 63-69 years) whose leading clinical presentation included the presence of constitutional symptoms and significantly elevated inflammatory markers. The diagnosis of LV-GCA was confirmed by CT angiography and FDG-PET/CT, revealing inflammation in the large vessels. All were treated with corticosteroids, while two received adjunctive therapy. By analyzing HLA profiles, we found no presence of the susceptible HLA-DRB1*04 allele, while the HLA-DRB1*15 allele was detected in two patients. In conclusion, LV-GCA may be triggered by COVID-19. We highlight the importance of the early identification of LV-GCA following SARS-CoV-2 infection, which may be delayed due to the overlapping clinical features of GCA and COVID-19. The prompt initiation of therapy is necessary in order to avoid severe vascular complications. Future studies will better define the role of specific HLA alleles in patients who developed GCA following COVID-19.

Effect and significance of hyperlipoproteinemia on stent thrombosis in patients with implanted drug-eluting stents: The 5-year follow up study.

BACKGROUND: Elevated blood lipid level, also known as hyperlipoproteinemia (HLP), is the most common metabolic disorder in the general population. According to US National Heart Institute data, about 36% of adults and 10% of children aged 9 to 12 have elevated cholesterol levels. The risk of ischemic heart disease increases by 2-3% with every 1% increase in total cholesterol levels. Therefore, men aged 55-65 with a 10% increase in total cholesterol have about 38% increased ischemic heart disease mortality. The study's main objective is to determine the occurrence of thrombotic complications in patients in whom first-generation drug-eluting stents are implanted and how these events are influenced by the presence of HLP. METHODS: The study is retrospective, clinical, and non-interventional with a five-year follow-up period for each patient. Initially, 800 patients undergoing index percutaneous coronary angioplasty with sirolimus-eluting and paclitaxel-eluting stent implantation were enrolled. Clinical data collected included cardiac disorders, the presence of diabetes mellitus, hyperlipoproteinemia, and smoking as a risk factor. In the examined group of patients, stent thrombosis was monitored according to Academic Research Consortium (ARC) criteria. RESULTS: The study included 800 patients who underwent percutaneous coronary angioplasty index. At the end of the follow-up period, 701 patients (87.6%) completed the clinical trial and were included in the statistical analysis. Stent thrombosis, determined according to ARC criteria, was reported as 'definitive stent thrombosis' in 22 patients (3.06%), 'probable stent thrombosis' in 1 patient (0.14%), and 'possible stent thrombosis' in 1 patient (0.14%). Of the 404 patients with HLP, 120 patients had a total cholesterol value >300 mg/dL. Twenty patients with definitive stent thrombosis had cholesterol >300 mg/dL. Patients with probable and possible stent thrombosis did not have HLP. A comparison of patients with stent thrombosis, with HLP and without HLP, revealed a statistically significant difference (16.67% vs. 1.35%, p <0.001). Comparing patients with unstable angina pectoris, with cholesterol value >300 mg/dL and without HLP, a statistically significant difference was observed (71.7% vs. 17.2%, p <0.001). CONCLUSIONS: We report on the long-term follow up of patients with stent thrombosis after drug-eluting stent insertion with and without HLP. The results suggest that HLP influences the development of coronary disease, with a significant influence on complications following percutaneous coronary intervention.

Gender motivational gap and contribution of different teaching approaches to female students' motivation to learn physics.

This research focuses on potential gender differences in motivation to learn Physics with the aim to determine the weakest female motivational components to learn Physics and the contribution of different teaching approaches (using real and virtual experiments) on those components and motivation for learning Physics in general. These two approaches were chosen as the most commonly used approaches in physics but without clear compared indication on females' motivation. The standardized questionnaire SMTSL (Student's Motivation towards Science Learning) is used for the measurements. The results show that for female students the weakest motivational components to learn Physics are the importance of Physics as a science and self-efficacy. Virtual experiments contribute more to females' motivation to learn Physics than applying real experiments. The female students who used real experiments show fear of being laughed at by their male peers and express doubt in their self-knowledge. Although the applied approaches cause some improvements in female students' self-efficacy, they are not statistically significant. Research results suggest that teachers need to apply such teaching approaches that engage girls and encourage their learning and development in order to improve their self-efficacy and other motivational components.

Prevalence of traditional cardiovascular risk factors for coronary artery disease and elevated fibrinogen among active military personnel in Republic of Serbia: A cross-sectional study.

Background: It is well known that less than 1% of the population achieves ideal cardiovascular health, and 65% of patients do not have their conventional risk biomarkers under control. Military service has its own particularities that may contribute to cardiovascular risk. Methods: To define the preventive strategy goals, we analysed the prevalence of traditional cardiovascular risk factors for coronary artery disease and elevated fibrinogen among active military personnel in the Republic of Serbia. Results: The cross-sectional study included 738 individuals older than 20 years, mostly between 31 and 40 years old. The mean value of SBP for the whole group was 122.39± 9.42 mmHg, and for the DBP, it was 79.94±6.56 mmHg. Among active military personnel, 72.7% (533) had prehypertension, and 13.8% (101) was hypertensive. Both body mass and BMI index among the observed age subgroups were found to increase with the age of the patients and cholesterol values. HDL cholesterol values also differed statistically significantly between age subgroups, with the proportion of individuals with HDL less than 1.5 mmol/L in all subgroups being about 85%, the only in the 41-50 age group was lower, 76.4%. LDL cholesterol and the proportion of individuals who had LDL 3.5 increases with the age of patients, and an identical trend was recorded with triglycerides. With ageing, fibrinogen levels increased. Conclusions: Those findings considering cardio and cerebrovascular risk factors would help create a new approach for primary prevention for these categories of individuals.

Genetic Aspects of Micronutrients Important for Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC) are complex diseases whose etiology is associated with genetic and environmental risk factors, among which are diet and gut microbiota. To date, IBD is an incurable disease and the main goal of its treatment is to reduce symptoms, prevent complications, and improve nutritional status and the quality of life. Patients with IBD usually suffer from nutritional deficiency with imbalances of specific micronutrient levels that contribute to the further deterioration of the disease. Therefore, along with medications usually used for IBD treatment, therapeutic strategies also include the supplementation of micronutrients such as vitamin D, folic acid, iron, and zinc. Micronutrient supplementation tailored according to individual needs could help patients to maintain overall health, avoid the triggering of symptoms, and support remission. The identification of individuals' genotypes associated with the absorption, transport and metabolism of micronutrients can modify future clinical practice in IBD and enable individualized treatment. This review discusses the personalized approach with respect to genetics related to micronutrients commonly used in inflammatory bowel disease treatment.

Autoimmune and immunoserological markers of COVID-19 pneumonia: Can they help in the assessment of disease severity.

Background: Immune dysregulation and associated inefficient anti-viral immunity during Coronavirus Disease 2019 (COVID-19) can cause tissue and organ damage which shares many similarities with pathogenetic processes in systemic autoimmune diseases. In this study, we investigate wide range autoimmune and immunoserological markers in hospitalized patients with COVID-19. Methods: Study included 51 patients with confirmed Severe Acute Respiratory Syndrome Coronavirus 2 infection and hospitalized due to COVID-19 pneumonia. Wide spectrum autoantibodies associated with different autoimmune inflammatory rheumatic diseases were analyzed and correlated with clinical and laboratory features and pneumonia severity. Results: Antinuclear antibodies (ANA) positivity was found in 19.6%, anti-cardiolipin IgG antibodies (aCL IgG) in 15.7%, and anti-cardiolipin IgM antibodies (aCL IgM) in 7.8% of patients. Positive atypical x anti-neutrophil cytoplasmic antibodies (xANCA) were detected in 10.0% (all negative for Proteinase 3 and Myeloperoxidase) and rheumatoid factor was found in 8.2% of patients. None of tested autoantibodies were associated with disease or pneumonia severity, except for aCL IgG being significantly associated with higher pneumonia severity index (p = 0.036). Patients with reduced total serum IgG were more likely to require non-invasive mechanical ventilation (NIMV) (p < 0.0001). Serum concentrations of IgG (p = 0.003) and IgA (p = 0.032) were significantly lower in this group of patients. Higher total serum IgA (p = 0.009) was associated with mortality, with no difference in serum IgG (p = 0.115) or IgM (p = 0.175). Lethal outcome was associated with lower complement C4 (p = 0.013), while there was no difference in complement C3 concentration (p = 0.135). Conclusion: Increased autoimmune responses are present in moderate and severe COVID-19. Severe pneumonia is associated with the presence of aCL IgG, suggesting their role in disease pathogenesis. Evaluation of serum immunoglobulins and complement concentration could help assess the risk of non-invasive mechanical ventilation NIMV and poor outcome.

The Diagnostic Importance of Recombinant Allergen IgE Testing in Patients with Hymenoptera Venom Allergy: Comparison of Two Methods.

Adults with systemic anaphylactic reactions (SAR) to insect sting show often multiple-positivity of serum-specific IgE (sIgE) to Hymenoptera venoms. Unnecessary long-lasting venom-specific immunotherapies (VIT) in false-positive patients increase the risk of recurrent SAR. This report aims to analyze the diagnostic importance of recombinant allergen IgE testing in patients with SAR to Hymenoptera sting. In 82 patients we measured sIgE to honeybee venom (HBV), wasp venom (WV) and hornet venom (HV) extracts, recombinant phospholipase A2 from HBV (sIgE-rApi m1), recombinant antigen 5 from WV (sIgE-rVes v5), and cross-reactive carbohydrate determinants-CCD-bromelain by ImmunoCAP. We analyzed the correlation of ImmunoCAP and Immunoblot for HBV and WV extracts, rApi m1, and rVes v5 in 39/82 patients. According to the history of the culprit insect, we compared sensitivity and specificity between the two methods. The severity of the SAR does not depend on the sIgE level to venom extracts and recombinant allergens. Fifty-one percent of the patients had a multiple-positivity to HBV/WV or HBV/WV/HV extracts. Severe SAR and CCD-sIgE were more frequent in multiple-positive than single-positive patients. CCD-sIgE were more frequent in HBV allergic patients than WV and HV allergic patients. There was a significant correlation between levels of sIgE to venom extracts and recombinant allergens measured by ImmunoCAP and Immunoblot. ImmunoCAP has higher sensitivity and specificity than Immunoblot for diagnosis of SAR to Hymenoptera venoms. IgE testing to recombinant CCD-free allergens is necessary for the adequate selection of long-lasting VIT, especially in patients with multiple sensitivities to venom extracts.

Major Aortic Reconstruction with the Replacement of Supra-Aortic Branches: Successful Surgical Treatment of Takayasu Arteritis Initially Presented as Congestive Heart Failure.

Takayasu arteritis (TA) is a rare, large vessel vasculitis that affects aorta, its major branches, and occasionally pulmonary arteries. Patients with TA can present with constitutional features and/or various symptoms and signs caused by morphological changes in the blood vessels affected by the inflammatory process. Corticosteroids (CS) and immunosuppressives (IS) are the first line treatment for active TA. Open surgery remains a treatment of choice for TA patients with moderate-to-severe aortic regurgitation (AR) and ascending aortic aneurysm (AAA). We present a 26-year-old female diagnosed with an advanced stage of TA, initially presented as congestive heart failure. Due to a progressive course of the disease (AR 3+, AAA 5.5 cm), surgery of the Aortic valve and root (Bentall procedure), with total arch reconstruction and replacement of supra-aortic branches was performed. The patient has had an uneventful recovery during the postoperative course with no complications at one year follow-up. Normal left ventricle (LV) diameter, LV ejection fraction 67%, and a trace of AR were seen on the last echocardiography.