Vogt-Koyanagi-Harada disease associated with interferon-A and ribavirin therapy for chronic hepatitis C infection

A rare case of Vogt-Koyanagi-Harada disease associated with ribavirin and interferon-alpha treatment for chronic hepatitis C infection is presented. The potential role of interferon and/or ribavirin therapy is discussed. Physicians should be aware of the association between interferon-alpha and ribavirin use for hepatitis C infection and the development of Harada's disease. Close monitoring of such patients for ocular side effects is necessary.     

Clinical Characteristics and Outcome of Primary Systemic Light-Chain Amyloidosis in Greece

Background:Primary systemic light-chain (AL) amyloidosis is characterized by the deposition of immunoglobulin light chain–derived amyloid fibrils in various tissues leading to multiorgan dysfunction.Patients and Methods:In order to define characteristics, treatment, and outcome of Greek patients with AL amyloidosis, we analyzed 112 unselected patients with AL from several hospitals.Results:The heart was involved in 59% of patients and kidneys in 71%. Patients were treated with several different treatment regimens; high-dose dexamethasone-based regimens were used as primary treatment in 43% and melphalan-based regimens in 37%, while 12% received up-front bortezomib with dexamethasone. A hematologic response to first-line therapy was documented in 50% (complete response, 14.5%), and organ responses were observed in 25% of patients, the latter being strongly associated with achievement of hematologic response. Median overall survival was 34.2 months and was independently affected by heart involvement, creatinine, age, involvement of ≥ 2 organs, and bone marrow plasmacytosis > 30%. In patients with cardiac involvement, advanced age and extended bone marrow plasmacytosis were associated with an even worse outcome, while for patients without heart involvement, only bone marrow plasmacytosis was independently associated with survival. Hematologic response was associated with improved survival in patients with heart involvement but mostly in patients with less bone marrow infiltration.Conclusion:In this first series of patients from Greece with AL amyloidosis, disease features and outcome appeared similar to those reported from tertiary centers. Heart involvement and bone marrow plasma cell infiltration comprise adverse prognostic factors but also indicate the heterogeneity of the disease and the need for individual treatment approaches.     

Susceptibility of Urinary Tract Bacteria to Fosfomycin

We evaluated the in vitro activity of fosfomycin against urinary isolates in a region in Greece that exhibits considerable antimicrobial resistance by evaluating retrospectively relevant susceptibility data retrieved from the microbiological library of the University Hospital of Heraklion, Crete, Greece. We examined 578 urinary isolates. In total, 516 (89.2%) were susceptible to fosfomycin; 415 isolates were gram negative, and 101 isolates were gram positive. Fosfomycin appears to exhibit good levels of in vitro activity against the examined urinary isolates.Urinary tract infections (UTIs) are among the commonest types of bacterial infections (13). The antibiotic treatment for UTIs is associated with important medical and economic implications (12, 17).Antibiotic agents such as beta-lactams, trimethoprim, and cotrimoxazole have been used for the treatment of UTIs (1, 22). However, the emergence of resistant uropathogens led to a shift to fluoroquinolones (18, 21, 26, 27), shorter antibiotic regimens (24, 39), and early switch practices (38). Yet, resistance to fluoroquinolones has been reported (14, 23). Additionally, the emergence of uropathogens, mainly Escherichia coli, exhibiting high rates of resistance due to the production of extended-spectrum beta-lactamases (ESBLs) is worrisome (30, 40).Fosfomycin is an old broad-spectrum bactericidal antibiotic agent that inhibits the synthesis of the bacterial cell. Its pharmacokinetic profile encourages its use for UTIs; the mean peak urinary concentration of an oral single dose of 3 g fosfomycin tromethamine occurs within 4 h, while concentrations sufficient to inhibit the majority of the urinary pathogens are maintained for 1 to 2 days (28). Thus, fosfomycin tromethamine has been approved as an oral single-dose treatment for acute uncomplicated cystitis (34, 39). Data from studies evaluating the role of fosfomycin in infections other than UTIs are also encouraging (8-11). We aimed to evaluate the in vitro activity of fosfomycin against urinary isolates isolated from patients in a 700-bed university hospital in Heraklion, Crete, Greece.The data included in our study were retrieved from the database of the microbiological laboratory of the University Hospital of Heraklion, Crete, Greece. We retrospectively tested fosfomycin susceptibility in all clinical urinary isolates that were collected over a 12-month period (January to December 2008). No specific criteria for the selection of isolates to be subjected to fosfomycin susceptibility testing had been set. Only the first isolate of each species per patient could be included in our study.Quantitative urine cultures were performed by standard techniques using Columbia blood and MacConkey agar plates (bioMérieux, Marcy l''Étoile, France). Plates were incubated for 18 to 24 h at 36°C. The bacterial species identification was performed by using standard biochemical methods, the API system, or the Vitek 2 automated system (bioMérieux, Marcy l''Étoile, France) (36). Antimicrobial susceptibility testing was performed using the disk diffusion method according to the Clinical and Laboratory Standards Institute (CLSI) (5). Due to the lack of acknowledged fosfomycin breakpoints for bacteria other than Escherichia coli and Enterococcus faecalis (2, 5, 33), we used the fosfomycin breakpoints for E. coli proposed by the CLSI for the remaining evaluated gram-negative isolates, a practice that was also followed by authors of similar studies (6). Similarly, we used the CLSI breakpoint regarding E. faecalis for the other evaluated gram-positive bacteria. Identification of ESBL-producing strains was performed by phenotypic testing based on the synergy between clavulanic acid and extended-spectrum cephalosporins (5). Carbapenemase production was detected by the modified Hodge test (29).A total of 578 clinical urinary isolates were included. Two-hundred seven (35.8%) of these 578 isolates originated from adult outpatients, 167 (28.8%) from patients hospitalized in medical wards, 74 (12.8%) from adult patients hospitalized in surgical wards, 17 (2.9%) from intensive care unit adult patients, 9 (1.5%) from adult patients in renal replacement therapy clinics, and 14 (2.4%) from patients from areas other than the above-mentioned hospital units. Ninety (15.5%) of the 578 isolates originated from pediatric patients. Eighty-six (95.5%) of these 90 isolates originated from pediatric inpatients.The 578 tested urinary bacterial isolates represented 456 (78.8%) gram-negative isolates and 122 (21.1%) gram-positive isolates. The 456 gram-negative isolates represented 404 (88.5%) members of the Enterobacteriaceae, 266 (65.8%) of which were Escherichia coli, and 52 (11.5%) of which were gram-negative, nonfermentative bacilli. The 122 tested gram-positive isolates consisted of 74 (60.6%) Enterococcus faecalis isolates, 16 (13.1%) Staphylococcus saprophyticus isolates, 13 (10.6%) Staphylococcus aureus isolates, 12 (9.8%) Enterococcus faecium isolates, 6 (4.9%) Streptococcus agalactiae isolates, and a single (0.8%) Staphylococcus epidermidis isolate. In total, 516 (89.2%) of the 578 tested urinary isolates were found to be susceptible to fosfomycin; 415 were gram negative, and 101 were gram positive. Specific data are presented in Table ​Table1.1. The above-mentioned group of 516 fosfomycin-susceptible urinary isolates included specific categories of resistant isolates. Specific data are presented in Table ​Table22.

TABLE 1.

Susceptibility to fosfomycin of gram-negative and gram-positive urinary isolates tested

Predicting variations to missed nursing care: A three‐nation comparison

Aims

To measure and model Australian, Cypriot and Italian nurses’ beliefs about what care is missed and how frequently it occurs within their settings.

Background

This study expands on previous MISSCARE research but now applies and predicts missed care within three countries.

Methods

Multivariate analysis was performed to estimate 1,896 nurses’ consensus scores about missed care activities based on Alfaro‐Lefevre's conceptual framework of care priorities.

Results

Five latent variables have direct predictor effects on missed care frequencies. Another four variables including the nurses’ age, highest qualifications, absenteeism rate and workplace type, contributed to explaining the overall variance of missed care scores. The nurses’ gender had no influence on missed care.

Conclusion

Cross country comparisons of missed nursing care allow for a more refined identification of strategies for remediation for both managers and clinicians.

Implications for Nursing Management

Reliable consensus estimates about the types and frequencies of missed care can be scaled with variables identified to predict missed care across three different countries. Comparative international studies build on the foundations for understanding missed care in terms of nursing practices, policies and related social policies.     

Proliferation and bone marrow engraftment of AML blasts is dependent on β-catenin signalling

B-catenin is the central effector molecule of the canonical Wnt signalling pathway, which controls self-renewal of haematopoietic stem cells. Deregulation of this pathway occurs in various malignancies including myeloid leukaemias. The present study examined the functional outcome of stable β-catenin down-regulation through lentivirus-mediated expression of short hairpin RNA (shRNA). Reduction of the β-catenin levels in acute myeloid leukaemia (AML) cell lines and patient samples decelerated their in vitro proliferation ability without affecting cell viability. Transplantation of leukaemic cells with control or reduced levels of β-catenin in non-obese diabetic severe combined immunodeficient animals indicated that, while the immediate homing of the cells was unaffected, the bone marrow engraftment was directly dependent on β-catenin levels. Subsequent examination of bone sections revealed that β-catenin was implicated in the localization of AML to the endosteum. Examination of adhesion molecule expression before and after transplantation, revealed down-regulation of CD44 expression, accompanied by reduced in vitro adhesion. Gene expression analysis disclosed the presence of an autocrine compensatory mechanism, which responds to the reduced β-catenin levels by altering the expression of positive and negative pathway regulators. In conclusion, our study showed that β-catenin comprises an integral part of AML cell proliferation, cell cycle progression, and adhesion, and influences disease establishment in vivo.     

IL-2 production by dendritic cells promotes Foxp3(+) regulatory T-cell expansion in autoimmune-resistant NOD congenic mice

Il2 allelic variation in non-obese diabetic mice imparts marked resistance to type 1 diabetes. IL-2 is pivotal for the fitness and homeostasis of Foxp3(+) regulatory T (T(reg)) cells, and the Idd3(B6) locus augments IL-2 production by effector T cells, which in turn enhances the potency of T(reg) cell functions. Given the important role dendritic cells (DCs) play in T(reg) cell-mediated tolerance induction, we hypothesized that DCs from Idd3(B6) congenic mice contribute to increased T(reg) cell activity. Here, we observed that CD11c(+) DCs, harboring protective Idd3(B6) genes, are endowed with the capacity to secrete IL-2, enabling them to preferentially promote T(reg) cell functions in vitro and in vivo. Our results show that Il2 gene variation may imprint DCs to favor T-cell regulation of autoimmunity.     

The role of the non-smoker in enforcing smoke-free laws

Compliance with laws making certain environments smoke free has focused mainly on smokers' behavior, while the role of non-smokers has scarcely been investigated. Our cross-sectional study interviewed 4043 adults (2037 smokers and 2006 non-smokers) in the general population of Greece during April 2009. Non-smokers reported that they would actively work for compliance with the law. The non-smokers were older, more educated (odds ratio, OR 1.4), and were more likely to be annoyed by the smell of environmental tobacco smoke (OR 2.4) or report that it irritates their eyes (OR 1.8). Policymakers should evaluate how non-smokers could actively support smoke-free laws through reporting of violations using media campaigns that inform them of their rights, and other measures.