Aspergillus peritonitis in peritoneal dialysis patients: A systematic review.

Fungal peritonitis in patients undergoing peritoneal dialysis (PD) is very difficult to treat and is associated with significant morbidity and mortality. Among fungal pathogens, Aspergillus peritonitis presents a higher mortality rate when compared to Candida peritonitis and its identification as well as appropriate treatment remains a challenge for the physicians. We critical reviewed all published cases in literature of Aspergillus peritonitis in PD patients. The results showed that a total of 55 cases (51% males) of Aspergillus peritonitis in PD patients were reported from 1968 to 2019. Mean patient age was 49.54±19.63years and mean PD duration prior to fungal infection was 33.31±32.45months. Aspergillus fumigatus was isolated in 17/55 patients, Aspergillus niger in 15, Aspergillus terreus in 9, unidentified Aspergillus spp. in 6, Aspergillus flavus in 4, whereas sporadic cases of other Aspergillus spp. were reported. As far as predisposing factors are concerned, 75% of patients suffered from prior bacterial peritonitis receiving antimicrobial therapy. Initial antifungal treatment was intravenous and/or intraperitoneal administration of amphotericin B formulations monotherapy in 47.2% of patients or in combination with fluconazole in 13.2%, or with itraconazole in 13.2%, or with caspofungin in 3.8%, or with ketoconazole or with 5-FC in 1.9%, each. Peritoneal catheter removal was performed in 85.5% of cases. Mortality rate was 38.2%, while 81.8% of the survived patients switched to hemodialysis. Conclusively, Aspergillus peritonitis diagnosis can be difficult, due to unspecific symptoms. Early treatment with appropriate antifungal agents can be determinant for patient prognosis. Despite appropriate treatment, reported mortality remains high.

Matrix metalloproteinases in ureteropelvic junction obstruction.

BACKGROUND: Management of ureteropelvic junction obstruction (UPJO) remains controversial. The aim of the present study was to measure the levels of matrix metalloproteinases (MMPs) in UPJO patients who were planned to undergo surgery and thus clarify if MMPs levels could serve as potential biomarkers of surgical obstruction in UPJO. METHODS: Serum samples of infants with UPJO diagnosis were compared to serum samples of healthy age-matched controls. MMP2 and MMP9 were quantified using enzyme-linked immunosorbent assay (ELISA). RESULTS: A total of 17 infants with UPJO diagnosis, and median age 1.5 months, were prospectively recruited. MMP9 levels were significantly decreased in the serum samples of UPJO infants compared to controls (p =0.037). Also MMP2 values were higher in UPJO infants compared to controls, but the difference was not statistically significant (p =0.206). CONCLUSIONS: This study found decreased concentrations of MMP9 in infants with obstructive hydronephrosis. However, the results should be tested in larger population samples and even be evaluated simultaneously with urine samples in order to delineate the ability of MMPs to serve as obstruction biomarkers. HIPPOKRATIA 2017, 21(3): 136-139.

Perilobar nephroblastomatosis: natural history and management.

Nephroblastomatosis (NB) has been considered as a precursor of Wilms tumor (WT). The natural history of NB seems to present significant variation as some lesions may regress spontaneously, while others may grow and expand or relapse and develop into WT later in childhood. Although, most investigators suggest adjutant chemotherapy, the effect and duration of treatment are not well established. Children with diffuse perilobar NB, Beckwith-Wiedemann syndrome, and hemihypertrophy seem to particularly benefit from treatment. We discuss our experience on two cases of NB and we review the literature for the management of this rare condition.

Nutrition assessment of children with advanced stages of chronic kidney disease-A single center study.

BACKGROUND: Malnutrition is a major problem among children with Chronic Kidney Disease (CKD) and it is essential to be recognized as early as possible. Aim of our study was to assess the nutrition status of children with CKD. METHODS: Nutrition status of 30 children (1-16 years) with CKD stages IIIV and on peritoneal dialysis was evaluated. Malnutrition risk was assessed by Pediatric Digital Scaled MAlnutrition Risk screening Tool (PeDiSMART) score software.Anthropometry was expressed as Z-scores for age and sex. Phase angle (PhA) and body cell mass were assessed by bioelectrical impedance analysis (BIA). Three-day food intake was recorded and analyzed. Biochemical indexes were assessed. RESULTS: Depending on the marker used for assessment 20-40% of our patients were malnourished. Intake/requirements ratio (median) was 86.5% for actual energy intake and 127% for actual protein intake. Multiple regression analysis has shown that the most determinant factor for Mid Upper Arm Circumference (MUAMC) was actual protein intake, Glomerular Filtration Rate (GFR) and age at diagnosis. PhA was mainly affected by GFR and energy intake. Statistically significant inverse correlation was found between PeDiSMART score and PhA (p=0.001), MUAMC (p=0.008) as well as protein intake (p=0.016). CONCLUSIONS: A considerable proportion of children with advanced CKD are undernourished. Regular dietitian evaluation based on novel tools as PeDiSMART score and PhA may identify earlier patients at risk for malnutrition. Hippokratia 2014; 18 (3): 212-216.

Peritonitis due to uncommon gram-positive pathogens in children undergoing peritoneal dialysis.

Peritonitis is still the main complication of peritoneal dialysis (PD) in children. Staphylococcus, especially Staphylococcus epidermidis and Staphylococcus aureus, are the predominant species isolated, followed by Streptococcus spp. and by far by gram-negative bacteria and fungi. We describe three cases of PD-related peritonitis in pediatric patients due to uncommon gram-positive pathogens, which were treated with intraperitoneal antibiotic agents.

Transfusion-related acute lung injury management in a pediatric intensive care unit.

Transfusion-related acute lung injury (TRALI) constitutes a life threatening complication of blood transfusion. In severe TRALI cases supportive care with mechanical ventilation in intensive care unit is needed. We present two severe TRALI cases caused by leukocyte depleted, ABO compatible, packed red blood cell transfusions, coming from multiparous women donors. In the first case diagnosis was based on clinical findings and established by the identification of leukocyte antibodies in donor's unit and recipient's serum and she deal with invasive mechanical ventilation. In the second case, diagnosis was based on clinical criteria and chest radiograph findings and non-invasive mechanical ventilation was used. Both cases were treated in a Pediatric Intensive Care Unit and they had a favorable outcome.

Oseltamivir-resistant influenza A pandemic (H1N1) 2009 virus in Northern Greece.

Resistance to oseltamivir was observed to influenza A pandemic (H1N1) 2009 virus strains, isolated from two patients in North Greece. Investigations showed resistant viruses with the neuraminidase (NA) 275Y genotypes. Pandemic A (H1N1) 2009 virus should be closely monitored for emergence of resistant variants.

H1N1 influenza A infection.

The 2009 flu outbreak in humans, known as "swine influenza" or H1N1 influenza A, refers to influenza A due to a new H1N1 strain called swine-origin influenza virus A (S-OIV). The new swine flu virus is actually a genetic mixture of two strains, both found in swine, of unknown origin. S-OIV can be transmitted from human to human and causes the normal symptoms of influenza. Prevention of swine influenza spread among humans includes use of standard infection control measures against influenza and constitutes the main scope of World Health Organization. For the treatment of S-OIV influenza oseltamivir and zanamivir are effective in most cases. Prophylaxis against this new flu strain is expected through a new vaccine, which is not available yet. Worldwide extension of S-OIV is a strong signal that a pandemic is imminent and indicates that response actions against S-OIV must be aggressive.

Mutation analysis a prerequisite for prenatal diagnosis of L-2-hydroxyglutaric aciduria?

The prenatal diagnosis of two subsequent pregnancies of the mother of a patient homozygous for a mutation in the L-2-hydroxyglutarate dehydrogenase gene is described. In the first pregnancy, measurement of L-2-hydroxyglutaric acid in amniotic fluid revealed an affected fetus. This pregnancy was terminated. In the prenatal diagnosis of the second pregnancy, mutational analysis was also included and proved to be of pivotal importance. Despite mildly increased levels of L-2-hydroxyglutaric acid in the amniotic fluid, the fetus was heterozygous for this mutation thus excluding L-2-HGA.

Effects of lipid formulations of amphotericin B on activity of human monocytes against Aspergillus fumigatus.

The immunomodulatory effects of liposomal amphotericin B (LAMB), amphotericin B lipid complex, and amphotericin B colloidal dispersion (ABCD) on antifungal activity of human monocytes (MNCs), an important component of antifungal host defense, against Aspergillus fumigatus were compared to those of deoxycholate amphotericin B (DAMB). MNCs from healthy volunteers were incubated with 1 or 5 microg/ml DAMB and 5 or 25 microg/ml lipid formulations for 22 h. Drug-pretreated or untreated MNCs were then washed and assayed for the following: (i) activity against A. fumigatus hyphae by XTT assay at MNC:hypha ratios of 10:1 and 20:1; (ii) production of superoxide anion (O2-) from MNCs in response to hyphae by cytochrome c reduction; (iii) production of hydrogen peroxide (H2O2) and H2O2-dependent intracellular intermediates (DIIs), such as OH- and HOCl, from MNCs in response to A. fumigatus culture supernatant by flow cytometric measurement of dihydrorhodamine-1,2,3 oxidation. With the exception of 1 microg/ml DAMB and 5 mug/ml LAMB or ABCD at 10:1, all amphotericin B formulations at both concentrations and MNC:hypha ratios enhanced MNC-induced damage of A. fumigatus hyphae compared to results with untreated cells (P < 0.01). While MNC O2- production upon hyphal challenge, an early event in oxidative burst, was not affected by the drugs, production of H2O2 and DIIs, late events, were significantly increased by all four drugs (P < 0.01). At clinically relevant concentrations, both conventional amphotericin B and its lipid formulations enhance antihyphal activity of MNCs against A. fumigatus in association with significant augmentation of H2O2 and DIIs but not O2-, further demonstrating the immunomodulatory antifungal activities of these agents.

Survey of neonatal candidiasis in Greece.

In order to estimate the extent of neonatal candidiasis in Greece and to identify trends in clinical management, the present study was conducted using a questionnaire directed to Greek neonatologists and pediatric infectious disease specialists. The respondents represented 15 hospitals in the country's seven largest cities, which are currently the only Greek cities with neonatal intensive care units. Based on the responses, the incidence of neonatal candidiasis was determined to be 1.87 and 1.94 cases per unit-year for the years 2001 and 2002, respectively. Although a shift toward the isolation of non-Candida albicans isolates was noted, C. albicans was still the predominant pathogenic species. Deoxycholate amphotericin B remains the most frequently used antifungal agent in neonatal units nationwide.

Differential expression of cytokines and chemokines in human monocytes induced by lipid formulations of amphotericin B.

The immunomodulatory effects of liposomal amphotericin B (LAMB), amphotericin B lipid complex (ABLC), and amphotericin B colloidal dispersion (ABCD) on mRNA and protein profiles of five cytokines and chemokines expressed by human monocyte-enriched mononuclear leukocytes (MNCs) were comprehensively evaluated by semiquantitative reverse transcription-PCR and enzyme-linked immunosorbent assays; they were compared to those of deoxycholate amphotericin B (DAMB). mRNAs of interleukin-1beta (IL-1beta), IL-1 receptor antagonist (IL-1ra), tumor necrosis factor alpha (TNF-alpha), monocyte chemotactic protein 1 (MCP-1), and macrophage inflammatory protein 1beta (MIP-1beta) were assessed after treatment of MNCs with each drug for 0.5, 2, 6, and 22 h. The cytokine protein profiles were obtained after incubation of MNCs with the drugs for 2 h (TNF-alpha) or 6 h (all the others). In the mRNA studies, DAMB resulted in an early increase of inflammatory cytokines or chemokines IL-1beta, TNF-alpha, MCP-1, and MIP-1beta (2 to 6 h) and in a late increase of anti-inflammatory IL-1ra (22 h). ABCD showed a general similar trend of inflammatory gene up-regulation. LAMB and ABLC decreased or did not affect IL-1beta and TNF-alpha, whereas ABLC additionally decreased MIP-1beta. In protein measurement studies, DAMB and ABCD up-regulated production of IL-1beta (P < 0.05), decreased the IL-1ra/IL-1beta ratio, and up-regulated the production of MCP-1 and MIP-1beta. In comparison, LAMB and ABLC down-regulated or did not affect the production of these cytokines/chemokines compared to untreated MNCs; furthermore, ABLC tended to increase the IL-1ra/IL-1beta ratio. These studies demonstrate that amphotericin B formulations differentially affect gene expression and release of an array of proinflammatory and anti-inflammatory cytokines that potentially may explain the differences in infusion-related reactions and dose-dependent nephrotoxicity as well as modulation of the host immune response to invasive fungal infections.

Neonatal candidiasis: analysis of epidemiology, drug susceptibility, and molecular typing of causative isolates.

A prospective observational study of invasive candidiasis was conducted in the neonatal intensive care unit of Aristotle University in Hippokration Hospital between 1994 and 2000. During this period, 59 neonates developed invasive candidiasis (58 cases of candidemia and 1 case of peritonitis), resulting in an overall incidence of 1.28% that showed a decreasing trend over the study period. Eleven (18.6%) cases developed within the first week of life and the others within a mean (+/-SEM) of 13.4+/-1.7 days after birth. The three most frequent causative species were Candida albicans (65.5%), Candida parapsilosis (15.5%), and Candida tropicalis (7%). C. albicans was the predominant species between 1994 and 1998, whereas, non-albicans Candida spp., particularly C. parapsilosis, were the most frequent species during the period 1999-2000 (P<0.001). While the overall mortality due to candidemia was 29% (17 of 59 cases), mortality associated with C. albicans and C. parapsilosis was 39.5% and 11.1%, respectively (P=0.032), and that observed in the 1999-2000 period was 0% (P=0.011). Virtually all isolates were susceptible to amphotericin B, flucytosine, fluconazole, and itraconazole, and no increases in minimal inhibitory concentrations were observed during these years. With the exception of a limited cluster of cases due to genotypically identical isolates, no clonal relation of C. albicans isolates was found. Moreover, no clonal persistence of C. albicans and no decrease in antifungal drug susceptibility occurred over the 6-year study period. Non-albicans Candida spp., mostly C. parapsilosis, have emerged as important pathogens in neonatal intensive care units, with infected patients having better outcomes as compared to patients infected with C. albicans.

Femoral osteomyelitis due to Aspergillus nidulans in a patient with chronic granulomatous disease.

13 cases of osteomyelitis caused by Aspergillus nidulans have been previously reported in patients with chronic granulomatous disease (CGD). All of them have been associated with simultaneous pulmonary infection and have had an extremely poor outcome. We report an unusual case of femoral osteomyelitis due to A. nidulans in a 16-year-old male with CGD, without pulmonary involvement. Treatment with liposomal amphotericin B and granulocyte colony-stimulating factor as well as extensive surgical debridement followed by prolonged treatment with itraconazole resulted in an excellent clinical response.