A retrospective study evaluating the impact of infectious complications during azacitidine treatment.

Azacitidine has become an available therapy for high-risk myelodysplastic syndromes. Infectious complications (IC) may impede the success of therapy. Since most patients are managed in an outpatient setting, often with low level of clinical and microbiological documentation, the impact of IC remains unclear. We retrospectively evaluated the clinical course of 77 patients with MDS treated with azacitidine between 2004 and 2015 (median age 69 years). Clinical workup included severity and type of IC, days in the hospital and with antimicrobial therapy, response to azacitidine, and overall survival (OS). In total, 614 azacitidine cycles were administered, 81 cycles with at least one IC. The median number of administered cycles was 6 (range 1-43). Median OS after the start of azacitidine was 17 months (range 1-103). Infection rates were higher in the first 3 cycles with bacterial infections leading. The better patients' hematological response to azacitidine with less IC occurred, and fewer days with antimicrobial treatment were needed. Compared to progressive disease, stable disease made no significant improvement in occurrence of IC and days in the hospital. Older age was associated with more IC and longer time in the hospital. Comorbidities or IPSS-R had no influence on IC. The incidence of IC correlated with hematological response and age. Stable disease led to longer OS, but incidence of IC was comparable to progressive disease and survival seemed to be bought by a considerable number of IC. IC rates were highest in the first 3 cycles. We recommend response evaluation after 4-6 cycles.

A novel comprehensive set of fungal Real time PCR assays (fuPCR) for the detection of fungi in immunocompromised haematological patients-A pilot study.

Fungal infections are recognized in an increasing number of patients with immunological deficits and are associated with high rates of mortality (Brown et al., 2012a). In this pilot-study, a rapid Real time PCR (fuPCR) was designed for the detection and differentiation of fungal pathogens in clinical specimens of haematological patients. The fuPCR, targeting the internal transcribed spacer region 2 (ITS2) of rDNA region, is comprised of seven multiplex reactions, which were shown to be specific and sensitive for a comprehensive spectrum of clinically relevant fungal species. This was validated by testing respective fungal DNAs in each fuPCR reaction and 28 respiratory samples of fungal pneumonia-proven patients. Clinical sample sets of throat swab, EDTA-blood and blood sera from 50 patients with severe haematological malignancies, including haematopoietic stem cell transfer (HSCT), and samples from 30 healthy individuals were then analysed. In a first step, 198 samples of immunosuppressed patients were solely examined by fuPCR; and 50.8% (33/65) respiratory swabs, 4.8% (3/63) EDTA blood samples and 1.4% (1/70) blood serum samples were tested positive. In a second step, 56 respiratory samples of immunosuppressed patients and 30 of healthy individuals were simultaneously analysed by fuPCR and standard cultivation techniques. By both methods 30.4% (17/56) swabs of the immunocompromised patients were tested positive, 37.5% (21/56) were tested negative and 32.1% (18/56) were tested fuPCR positive and culture negative. In analysing the blood samples of the immunocompromised patients 5.4% (3/56) EDTA blood samples and 16.1% (9/56) sera samples were tested fuPCR-positive, whereas all samples of 30 healthy individuals with no signs of immunological deficits were tested negative by fuPCR. 38.9% (14/36) of the fungi detected in respiratory samples of the immunosuppressed patients, belonged to Candida spp., 47.2% (17/36) to Saccharomyces spp., 5.6% (2/36) to Cladosporium spp. and 8.3% (3/36) to Alternaria spp., whereas cultivation only identified Candida spp. (10/17) and Saccharomyces spp. (7/17). In this pilot study a novel fuPCR assay was developed and validated for the simultaneous and comprehensive detection of fungal pathogens in clinical respiratory specimens of haematological patients. Future work will focus on the validation of the blood-stream detected fungi in pathogenicity of these patients.

Objective parameters aid the prediction of fistulas in pancreatic surgery.

Insufficiency of pancreatic anastomosis with leakage from the pancreatic stump and the development of fistulas account for the majority of surgical complications following pancreatic resection, which are often life threatening. The cause of pancreatic fistulas of the remnant tissue on a molecular level remains unclear. Thus, the aim of the present study was to investigate risk factors associated with postoperative pancreatic fistula (POPF) formation and to define parameters that may predict the resection outcome. Pancreatic resection margins were selected from 31 patients, including 16 individuals without and 15 patients with POPF, to analyze the degree of fibrosis, lipomatous atrophy, inflammatory activity and infiltration. Wound healing factors were assessed by luminex technology using tissue homogenates, while the distribution in situ was assessed using immunohistochemistry. Increased chronic inflammatory infiltration, a higher degree of fibrosis and a reduction in lipomatous atrophy were observed in the samples without anastomotic fistulas. Multiplex analysis of 38 wound healing factors demonstrated significantly higher levels of interleukin (IL)-6, -8 and -12, glucagon-like peptide-1 and matrix metalloproteinase (MMP)-1, -2, -3 and -12 in the group without fistulas, while lower concentrations of IL-10, IL-17 and gastric inhibitory polypeptide were observed. Therefore, the observations of the present study indicated that increased inflammatory infiltration and inflammatory activity, as well as higher concentrations of proinflammatory cytokines and higher MMP levels at the resection margins, predisposed individuals to a lower fistula incidence rate following pancreatic resection.