Ioannis Kyriakidis

Serum TNF-α, sTNFR1, IL-6, IL-8 and IL-10 levels in Weil's syndrome.

Studies on cytokine levels in Weils syndrome are lacking. In this study, TNF-α, sTNFR1, IL-6, IL-8 and IL-10 levels were measured in 44 serum samples of patients diagnosed with Leptospira interrogans serovar icterohaemorrhagiae infection. TNF-α levels linked with pulmonary hemorrhagic implications, while elevated sTNFR1 and IL-10 levels linked with fatal cases. IL-6 and IL-8 did not seem to affect the outcome of the disease. Immune response pattern in Weils syndrome bears resemblance to other patterns described for hemorrhagic fevers. IL-10/TNF-α ratio is proposed as a marker for prognosis.

Clinical hepatotoxicity associated with antifungal agents.

ABSTRACT Introduction: Invasive fungal diseases (IFDs) are a leading cause of morbidity and mortality among immunocompromised patients with bone marrow failure syndromes, hematological malignancies, hematopoietic stem cell transplantation (HSCT), those admitted in intensive care units (ICUs) and those with prolonged febrile neutropenia. IFDs occur in a setting of multiple morbidities and are associated with case fatality rates between 30 and 70%. Along with the development of classes and compounds, the last two decades have seen substantial improvements in the prevention and management of these infections and an overall increased use of antifungal agents. Areas covered: All antifungal agents, including amphotericin B formulations, echinocandins and the triazoles, may cause hepatic toxicity that ranges from mild and asymptomatic abnormalities in liver function tests to substantial liver injury and fulminant hepatic failure. Expert opinion: The present article reviews incidence and severity of hepatotoxicity associated with different classes and agents to provide a better understanding of this specific end organ toxicity and safer use of antifungal agents A thorough understanding of the distribution, metabolism, elimination and drug-drug interactions of antifungal agents used for management of IFDs in combination with safety data from clinical trials, pharmacokinetic and pharmacodynamic studies may guide the use of antifungal treatment in patients at high risk for the development of hepatic dysfunction and in those with underlying liver damage due to cytotoxic therapy.

Decreasing Prevalence of Alcohol Consumption Among Greek Adolescents

Aim of this study: To obtain data on alcohol consumption among school children of secondary education and to investigate any correlation to their health behaviors and parental socioeconomic status. Methods: A questionnaire was distributed to students from a representative sample of 15 schools from Thessaloniki, the second (after Athens) largest metropolitan city of Greece. A total of 1185 students (505 males, 680 females) participated. Results: 286 males (56.6%) and 329 females (48.4%) reported consuming alcohol. The initiation of drinking was at the age of 13.2 years for boys and 13 years for girls. Alcohol drinking was positively associated with socio-demographic variables and negative health behaviors such as parental low level of education, lack of physical exercise, coffee consumption, and smoking. Conclusions: Although our results show a decrease in alcohol use, which is more pronounced in male students, the prevalence of frequent alcohol consumption is among the highest in Europes countries.

Serum TNF-α, sTNFR1, IL-6, IL-8 and IL-10 levels in hemorrhagic fever with renal syndrome.

It is generally accepted that the pathogenesis of hantavirus infections is the result of virus-mediated host immune response. Hantaviruses, and mainly Dobrava-Belgrade virus, are present in Greece, and cause to humans hemorrhagic fever with renal syndrome (HFRS). Serum IL-6, IL-8, IL-10, TNF-α and sTNFR1 levels were measured in 29 HFRS Greek patients. Significant higher sTNFR1, IL-6, IL-8 and IL-10 levels were observed in severe than in mild/moderate cases, while TNF-α did not seem to be associated with disease severity. Correlations between cytokine levels and their fluctuation over time after onset of the illness, along with comparisons from previously published data on the field, led in building an immune response pattern for HFRS.

Estrogen receptor beta and ovarian cancer: a key to pathogenesis and response to therapy

AbstractIntroduction Ovarian cancer remains the leading cause of mortality due to gynecological tumors. Estrogen receptors (ERs) seem to participate in tumor progression even in the absence of estrogens. Twenty years after the cloning of the second estrogen receptor, a wide spectrum of studies have shown its implication in both physiologic and pathologic pathways. ERβ, being the predominant type of ER in normal ovary tissue, has not only been linked with pathogenesis of ovarian cancer, but also with response to treatment. Unlike ERα, which is primarily linked with cell growth, ERβ presence is prominent in signaling pathways, cell cycle regulation and apoptosis.MethodsLiterature review of relevant published material (from PubMed, Scopus, and Cochrane databases) was conducted.ResultsPolymorphisms in the respective ESR2 gene, epigenetic modifications and isoforms of the receptor have been extensively studied to assess potential correlations with responsiveness to treatment and tumor behavior. Studies on the exact roles of ERβ and its genetic variations in altering effectiveness and toxicity of ovarian cancer treatment regimens are lacking.ConclusionClinical utilization of ERβ actions in the management of ovarian cancer is discussed in an up-to-date review.

Invasive fungal infections in pediatric patients treated with tumor necrosis alpha (TNF-α) inhibitors

Macromolecular immunosuppressive monoclonal antibodies and fusion proteins directed against molecules or cells involved in inflammation and immunity represent a recent and important addition to our therapeutic armamentarium. Tumor necrosis alpha (TNFα) is a cytokine involved in systemic inflammation and clinical utilization of its antagonists has revolutionized treatment of juvenile rheumatoid and psoriatic arthritis, ankylosing spondylitis, Crohns disease, ulcerative colitis, and plaque psoriasis. Clinical utility has also been demonstrated for use against steroid‐refractory graft‐vs‐host disease and other immune‐mediated conditions. Currently, five anti‐TNFα agents are approved by the European Medicines Agency (EMA), including the monoclonal anti‐TNF antibodies infliximab, adalimumab, golimumab and certolizumab pegol along with etanercept, a TNFα‐receptor/IgG‐Fc fusion protein. Theoretical considerations related to their mode of action and clinical observations suggest that opportunistic infectious complications should be seriously considered as possible adverse events of macromolecular immunosuppressants. The purpose of this review is to critically analyze the literature on invasive fungal infections (IFIs) occurring in association with TNFα inhibitors alone or in combination with other immunosuppressive agents, with a focus on pediatric patients, and to provide a framework of evaluating the risk for IFIs in this population.

Lumbar puncture complicated by spinal epidural hematoma in a child with leukemia

We report a case of spinal epidural hematoma (SEH) preceded by diagnostic lumbar puncture (LP) in a 5‐year‐old boy with acute lymphoblastic leukemia. MRI confirmed the presence of SEH between T7 and L5 levels, but the patient showed fast recovery during the next hours and conservative management was elected.

Invasive fungal infections in paediatric patients treated with macromolecular immunomodulators other than tumour necrosis alpha inhibitors

An expanding list of immunomodulatory or immunosuppressive monoclonal antibodies (mAbs) and biologic therapeutics is currently entering clinical practice, particularly in the areas of oncology, transplantation and autoimmune disorders. These agents are directed against molecules or cells involved in inflammation and immunity and may therefore be associated with serious and opportunistic infections. The purpose of this review was to critically analyse the literature on invasive fungal infections (IFIs) occurring in association with mAbs and fusion proteins other than tumour necrosis alpha (TNF‐α) inhibitors, including therapeutics modulating T‐cell‐mediated pathologies (muromonab, abatacept, belatacept, ipilimumab, basiliximab, daclizumab), inducing lymphopenia (alemtuzumab), depleting CD20+ B cells (rituximab) and interfering with various targets (anakinra, natalizumab, blodalumab, ixekizumab and others) with a focus on children, and to provide a framework of evaluating the risk for IFIs in this population.

A 13-Year-Old Child with Lupus-Like Nephritis and 22q11 Microduplication Syndrome.

To the Editor Dear Editor-In-Chief, Based on a recently published case in your journal concerning the immunodeficiency profile of a child with 22q11.2 microduplication syndrome by Traynor et al. [1], we could like to present an additional interesting case of a 13-year-old Caucasian male with lupus-like nephritis, recurrent episodes of infections, congenital heart defect, and microduplication at the 22q.11 distal region diagnosed with comparative genomic hybridization (CGH) array. Our case, which is to our knowledge the first one published with autoimmune lupus-mediated nephritis, reinforces the hypothesis that patients with 22q11.2 microduplication syndrome might present an increased risk of recurrent infections and various autoimmune phenomena. Bearing in mind the rarity of the present syndrome, we would recommend clinical awareness of these risks and further investigation in patients with 22q11.2 genetic disorders. Microduplication 22q11 syndrome has been recently characterized as a new genomic syndrome having only few overlapping features compared with the classic DiGeorge/ velocardiofacial syndrome [2]. The 22q11 syndrome shows wide phenotypic variability ranging from normal to multiple congenital defects including heart defects and urogenital abnormalities [2]. Herewith, we describe the first 13-yearold Caucasian male case with lupus-like nephritis, recurrent infections, congenital heart defect, and microduplication at the 22q.11 distal region. A 13-year-old Caucasian male was admitted for prolonged macroscopic painless hematuria, without a recent history of trauma or infection. The child was hemodynamically stable, with elevated blood pressure (stage I). The patient’s medical history revealed congenital heart disease, common patent ductus arteriosus, repaired at the age of 9 months with valvuloplasty. The child presented 5 years later subsequent graft stenosis and aortic valve insufficiency. At 7 years of age, the child was hospitalized due to staphylococcal endocarditis. Furthermore, the child had a history of four respiratory tract infection (RTI) episodes—two of them needed hospitalized treatment. There was no family history of autoimmune disorders. On admission to our hospital, initial laboratory and clinical findings excluded hemolytic phenomena and infection but revealed mild anemia (10.3 g/dl), leukopenia (4.900/μl), hypocalcemia (7.6 mg/dl), hematuria (40–50 red blood cells per high-power field), albuminuria (10 mg/m/h), impaired renal function with creatinine clearance of 96 ml/kg/1.73 m, elevated ESR (48 mm/1 h), D-dimers (940 ng/ml), and positive ANA autoantibodies (1/160). Complement/ASTO and Creactive protein were within the normal range. Serum immunoglobulin levels revealed elevation of IgG for his age (IgG 2550 mg/dl, IgA 532 mg/dl, IgM 266 mg/dl, IgE 143 IU/ml). Initial lymphocyte immunophenotyping from the peripheral blood revealed the following: CD3+ (77 %) 624 cells/μl, CD3+/CD4+ (46 %) 373, CD3/CD8 (30 %) 243, T4/T8 ratio of 1:5, CD19+ (14.4 %) 117 cells/μl, CD3−/(CD15/CD56)+ NK (6.3 %) 51, and CD3+/(CD15/CD56)+ NK (1.0%) 15. Due to worsening of the nephritic syndrome, renal biopsy was performed. Genetic testing was also preformed due to * Zoi Dorothea Pana panazoi@gmail.com; zpana1@jhmi.edu

Primary EBV infection and hypersensitivity to mosquito bites: a case report

Abstract