Prevention of legionella infections from toilet flushing cisterns.

INTRODUCTION: Immunocompromised patients are at an increased risk of severe legionella infections. We present the results of an outbreak investigation initiated following a fatal case of hospital-acquired legionellosis linked to contaminated water from a toilet-flushing cistern. Additionally, we provide experimental data on the growth of Legionella spp. in flushing cisterns and propose a straightforward protocol for prevention. METHODS: We monitored the growth of Legionella spp. in the building's hot- and cold-water systems using quantitative bacterial culture on selective agar. Molecular typing of Legionella pneumophila isolates from the infected patient and the water system was conducted through core-genome multi-locus sequence typing (cgMLST). RESULTS: Legionella contamination in the hospital building's cold-water system was significantly higher than in the hot-water system and significantly higher in toilet flushing cistern's water compared with cold water from bathroom sinks and showers. Isolates from the patient and from the flushing cistern of the patient's bathroom were identical by cgMLST. In an experimental setting, daily toilet flushing for a period of 21 days resulted in a 67% reduction in the growth of Legionella spp. in the water of toilet flushing cisterns. Moreover, a one-time disinfection of cisterns with peracetic acid, followed by daily flushing, decreased legionella growth to less than 1% over a period of at least seven weeks in these setting. CONCLUSIONS: One-time disinfection of highly contaminated cisterns with peracetic acid and daily toilet flushing as short-term measure can significantly reduce legionella contamination in flushing cisterns. These measures may aid in preventing legionella infection among immunocompromised patients.

Management of sepsis in neutropenic cancer patients: 2018 guidelines from the Infectious Diseases Working Party (AGIHO) and Intensive Care Working Party (iCHOP) of the German Society of Hematology and Medical Oncology (DGHO).

Sepsis and septic shock are major causes of mortality during chemotherapy-induced neutropenia for malignancies requiring urgent treatment. Thus, awareness of the presenting characteristics and prompt management is most important. Improved management of sepsis during neutropenia may reduce the mortality of cancer therapies. However, optimal management may differ between neutropenic and non-neutropenic patients. The aim of the current guideline is to give evidence-based recommendations for hematologists, oncologists, and intensive care physicians on how to manage adult patients with neutropenia and sepsis.

Consensus statement for cancer patients requiring intensive care support.

This consensus statement is directed to intensivists, hematologists, and oncologists caring for critically ill cancer patients and focuses on the management of these patients.

Diagnosis and management of gastrointestinal complications in adult cancer patients: 2017 updated evidence-based guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO).

Cancer patients frequently suffer from gastrointestinal complications. In this manuscript, we update our 2013 guideline on the diagnosis and management of gastrointestinal complications in adult cancer patients by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO). An expert group was put together by the AGIHO to update the existing guideline. For each sub-topic, a literature search was performed in PubMed, Medline, and Cochrane databases, and strengths of recommendation and the quality of the published evidence for major therapeutic strategies were categorized using the 2015 European Society for Clinical Microbiology and Infectious Diseases (ESCMID) criteria. Final recommendations were approved by the AGIHO plenary conference. Recommendations were made with respect to non-infectious and infectious gastrointestinal complications. Strengths of recommendation and levels of evidence are presented. A multidisciplinary approach to the diagnosis and management of gastrointestinal complications in cancer patients is mandatory. Evidence-based recommendations are provided in this updated guideline.

Influenza virus infections in patients with malignancies -- characteristics and outcome of the season 2014/15. A survey conducted by the Infectious Diseases Working Party (AGIHO) of the German Society of Haematology and Medical Oncology (DGHO).

Influenza virus infections (IVI) may pose a vital threat to immunocompromised patients such as those suffering from malignancies, but specific data on epidemiology and outcome in these patients are scarce. In this study, we collected data on patients with active cancer or with a history of cancer, presenting with documented IVI in eight centres in Germany. Two hundred and three patients were identified, suffering from haematological malignancies or solid tumours; 109 (54 %) patients had active malignant disease. Influenza A was detected in 155 (77 %) and Influenza B in 46 (23 %) of patients (genera not determined in two patients). Clinical symptoms were consistent with upper respiratory tract infection in 55/203 (27 %), influenza-like illness in 82/203 (40 %), and pneumonia in 67/203 (33 %). Anti-viral treatment with oseltamivir was received by 116/195 (59 %). Superinfections occurred in 37/203 (18 %), and admission on an intensive care unit was required in 26/203 (13 %). Seventeen patients (9 %) died. Independent risk factors for death were delayed diagnosis of IVI and bacterial or fungal superinfection, but not underlying malignancy or ongoing immunosuppression. In conclusion, patients with IVI show high rates of pneumonia and mortality. Early and rapid diagnosis is essential. The high rate of pneumonia and superinfections should be taken into account when managing IVI in these patients.

CNS infections in patients with hematological disorders (including allogeneic stem-cell transplantation)-Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO).

Infections of the central nervous system (CNS) are infrequently diagnosed in immunocompetent patients, but they do occur in a significant proportion of patients with hematological disorders. In particular, patients undergoing allogeneic hematopoietic stem-cell transplantation carry a high risk for CNS infections of up to 15%. Fungi and Toxoplasma gondii are the predominant causative agents. The diagnosis of CNS infections is based on neuroimaging, cerebrospinal fluid examination and biopsy of suspicious lesions in selected patients. However, identification of CNS infections in immunocompromised patients could represent a major challenge since metabolic disturbances, side-effects of antineoplastic or immunosuppressive drugs and CNS involvement of the underlying hematological disorder may mimic symptoms of a CNS infection. The prognosis of CNS infections is generally poor in these patients, albeit the introduction of novel substances (e.g. voriconazole) has improved the outcome in distinct patient subgroups. This guideline has been developed by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) with the contribution of a panel of 14 experts certified in internal medicine, hematology/oncology, infectious diseases, intensive care, neurology and neuroradiology. Grades of recommendation and levels of evidence were categorized by using novel criteria, as recently published by the European Society of Clinical Microbiology and Infectious Diseases.

Central venous catheter-related infections in hematology and oncology: 2012 updated guidelines on diagnosis, management and prevention by the Infectious Diseases Working Party of the German Society of Hematology and Medical Oncology.

BACKGROUND: Cancer patients are at increased risk for central venous catheter-related infections (CRIs). Thus, a comprehensive, practical and evidence-based guideline on CRI in patients with malignancies is warranted. PATIENTS AND METHODS: A panel of experts by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) has developed a guideline on CRI in cancer patients. Literature searches of the PubMed, Medline and Cochrane databases were carried out and consensus discussions were held. RESULTS: Recommendations on diagnosis, management and prevention of CRI in cancer patients are made, and the strength of the recommendation and the level of evidence are presented. CONCLUSION: This guideline is an evidence-based approach to the diagnosis, management and prevention of CRI in cancer patients.

Diagnosis and management of gastrointestinal complications in adult cancer patients: evidence-based guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO).

BACKGROUND: Cancer patients frequently suffer from gastrointestinal complications. However, a comprehensive, practical and evidence-based guideline on this issue is not yet available. PATIENTS AND METHODS: An expert group was put together by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO) to develop a guideline on gastrointestinal complications in cancer patients. For each subtopic, a literature search was carried out in PubMed, Medline and Cochrane databases and the strength of recommendation and the quality of the published evidence for major therapeutic strategies were categorized using a modification of the 'Infectious Diseases Society of America' criteria. Consensus discussions were held on each of the topics. RESULTS: Recommendations were made with respect to non-infectious and infectious gastrointestinal complications. For all recommendations, the strength of the recommendation and the level of evidence are presented. CONCLUSION: This guideline is an evidence-based approach to the diagnosis and management of gastrointestinal complications in cancer patients.

Use of capillary blood count parameters in adults.

BACKGROUND AND OBJECTIVES: Capillary samples can provide blood for cell counts in haematologic patients and blood donors. However, some accept only values from venous blood. This study compares capillary and venous blood counts to verify the hypothesis that they are equivalent. MATERIALS AND METHODS: We analysed 463 capillary (fingerstick) and venous blood samples from 428 adults of both sexes (71% haematologic patients, 29% potential blood and apheresis donors). Both samples were taken at the same time from each subject. Haemoglobin (Hb), haematocrit (Hct), white blood cells (WBC), platelets, red blood cells (RBC), mean corpuscular volume (MCV), mean corpuscular Hb (MCH) and mean corpuscular Hb concentration (MCHC) were measured using a haematology analyser (Advia 120, Bayer). RESULTS: Capillary Hb, Hct, WBC, RBC, MCV and MCH were all significantly higher than the venous values [+0.2 mmol/l (+0.3 g/dl), +0.02 l/l (+2%), +0.2 x 10(9)/l, +0.1 x 10(12)/l, +3.1 fl and +0.01 fmol, respectively], whereas the capillary MCHC was lower (-0.6 mmol/l). There was no difference in platelets (-1 x 10(9)/l). Capillary Hb and Hct values were higher in patients with anaemia and polycythaemia, respectively. However, no significant differences occurred in severe thrombocytopenia. CONCLUSION: In adult haematologic patients, however, only the differences in Hb and Hct values may be of clinical relevance. For potential blood and apheresis donors, Hb and platelet screening are equivalent with either capillary and venous blood using a haematology analyser.

Diabetes insipidus due to herpes encephalitis in a patient with diffuse large cell lymphoma. A case report.

The major causes of central diabetes insipidus are neoplastic or infiltrative lesions of the hypothalamus or pituitary, severe head injuries and pituitary or hypothalamic surgery. Central diabetes insipidus caused by viral infections has been rarely reported in immunosuppressed patients, such as those with acquired immunodeficiency syndrome or Cushing's syndrome. We report the case of a 48-year-old woman suffering from diffuse large cell lymphoma, who developed hypotonic polyuria, hypernatriaemia and somnolence after the first course of chemotherapy with CHOEP and rituximab. Diabetes insipidus was diagnosed by low urine osmolarity and an undetectable vasopressin concentration. MRI revealed no pituitary abnormalities but encephalitis, and lumbar punction confirmed herpes zoster infection. To the best of our knowledge this is the first description of central diabetes insipidus in a lymphoma patient caused by an opportunistic CNS-infection.

[Acute myeloid leukemia with pulmonary manifestation]. / Akute myeloische Leukämie mit pulmonaler Manifestation.

BACKGROUND: Extramedullary manifestations of leukemias are often misinterpreted. The prognosis of pulmonary manifested leukemias is poor. CASE REPORT: A 57-year-old female patient was admitted to our hospital because of refractory pneumonia and the suspicion of acute leukemia. The diagnosis of acute myeloid leukemia (AML, FAB M5a) was derived from bone marrow aspiration. The radiograph and the computed tomography of the chest showed infiltrations of both lungs. The cytologic aspect of a bronchoalveolar lavage was dominated by leukemic blasts, therefore AML with pulmonary manifestation was diagnosed. Cytotoxic therapy with cytarabine/idarubicin was combined with prednisolone. In the course of treatment the pulmonary function improved and radiographic alterations diminished significantly. After induction therapy complete haematological remission (CR) was shown by bone marrow aspiration. Two consolidation therapies followed. Unfortunately, the patient died four months after CR in a local hospital. CONCLUSIONS: The pulmonary manifestation of AML can be diagnosed by bronchoscopy. In contrast to the literature the initial course of the disease in this case was favourable possibly due to the addition of prednisolone to the cytotoxic treatment.

Post-transcriptional regulation of the pro alpha 1(I) collagen gene in pro alpha 1(I)-deficient, chemically transformed Syrian hamster embryo fibroblasts.

4-Nitroquinoline-1-oxide-transformed Syrian hamster embryo fibroblasts (NQT-SHE) synthesize the pro alpha 2 chain but not the pro alpha 1 subunit of type I procollagen, and they contain little pro alpha 1(I)mRNA. This study shows that there was no accumulation of pro alpha 1(I) poly(A)+ mRNA in NQT-SHE fibroblasts. BHK cells, a normal established line of hamster fibroblasts that synthesized collagen at approximately the same rate as NQT-SHE fibroblasts, nevertheless produced both subunits of type I collagen and contained pro alpha 1(I)mRNA. Run-off transcription assays with isolated nuclei showed that both the pro alpha 1(I) and pro alpha 2(I) genes were transcribed at about the same rate in NQT-SHE cells as well as in the normal BHK cells. These results suggest that a post-transcriptional defect, probably resulting from transformation, prevents the accumulation of pro alpha 1(I)mRNA in NQT-SHE cells.

Scorbutic and fasted guinea pig sera contain an insulin-like growth factor I-reversible inhibitor of proteoglycan and collagen synthesis in chick embryo chondrocytes and adult human skin fibroblasts.

Chick embryo chondrocytes cultured in sera from scorbutic and fasted guinea pigs exhibited decreases in collagen and proteoglycan production to about 30-50% of control values (I. Oyamada et al., 1988, Biochem. Biophys. Res. Commun. 152, 1490-1496). Here we show by pulse-chase labeling experiments that in the chondrocyte system, as in the cartilage of scorbutic and fasted guinea pigs, decreased incorporation of precursor into collagen was due to decreased synthesis rather than to increased degradation. There was a concomitant decrease in type II procollagen mRNA to about 32% of the control level. As in scorbutic cartilage, proteoglycan synthesis by chondrocytes in scorbutic serum was blocked at the stage of glycosaminoglycan chain initiation. Scorbutic and fasted guinea pig sera also caused a 50-60% decrease in the rates of collagen and proteoglycan synthesis in adult human skin fibroblasts, which synthesize mainly type I collagen. Decreased matrix synthesis in both cell types resulted from the presence of an inhibitor in scorbutic and fasted sera. Elevated cortisol levels in these sera were not responsible for inhibition, as determined by the addition of dexamethasone to chondrocytes cultured in normal serum. Insulin-like growth factor I (IGF-I, 300-350 ng/ml) reversed the inhibition of extracellular matrix synthesis by scorbutic and fasted guinea pig sera in both cell types and prevented the decrease in type II procollagen mRNA in chondrocytes. Therefore, in addition to its established role in proteoglycan metabolism, IGF-I also regulates the synthesis of several collagen types. An increase in the circulating inhibitor of IGF-I action thus could lead to the negative regulation of collagen and cartilage proteoglycan synthesis that occurs in ascorbate-deficient and fasted guinea pigs.

Uncoupled expression of mRNAs for alpha 1(I) and alpha 2(I) procollagen chains in chemically transformed Syrian hamster fibroblasts.

Syrian hamster embryo fibroblasts transformed by 4-nitroquinoline-1-oxide (NQT-SHE cells) failed to synthesize the pro-alpha 1(I) subunit of type I procollagen but continued to synthesize altered forms of the other subunit, pro-alpha 2(I) (Peterkofsky, B., and Prather, W. (1986) J. Biol. Chem. 261, 16818-16826). This was unusual, since synthesis of the two subunits generally is coordinately regulated. Present experiments using cell-free translation and hybridization of RNA from normal and transformed Syrian hamster fibroblasts with labeled pro-alpha 1(I) DNA probes show that mRNA for pro-alpha 1(I) is absent from the transformant. In contrast, dot-blot and Southern blot hybridizations of cellular DNAs with pro-alpha 1(I) DNA probes demonstrated that the transformed cells contained pro-alpha 1(I) gene sequences and that the gross structure of the gene was unchanged by transformation. mRNA for the other type I procollagen subunit, pro-alpha 2(I), was present in transformed cells and the major collagenous polypeptide translated from this RNA migrated like the normal pro-alpha 2 subunit during sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The translated procollagen chain was cleaved to an alpha 2(I)-sized collagen chain by pepsin at 4 degrees C. These studies provide a molecular basis for the observed collagen phenotype of NQT-SHE cells.

Effect of synthetic human parathyroid hormone on the levels of alkaline phosphatase activity and formation of alkaline phosphatase-rich matrix vesicles by primary cultures of chicken epiphyseal growth plate chondrocytes.

The effect of synthetic human parathyroid hormone (hPTH) on the formation of matrix vesicles (MV), and on the rate of cell division, production of cellular alkaline phosphatase (AP) and protein by primary cultures of chicken epiphyseal growth plate hypertrophic chondrocytes was investigated. Addition to serum-containing or serum-free media of physiological levels of hPTH, in a range from 0.1 to 10 nM, caused a progressive decrease in the formation of AP-rich MV. However, studies on incorporation of [3H]choline into MV indicate that MV formation per se was not significantly decreased. hPTH was found to markedly decrease the expression of cellular AP, accompanied by an increase in cell division [( 3H]thymidine incorporation) and protein synthesis. Since these effects of hPTH were augmented by 3-isobutyl-1-methylxanthine (IBMX), a phosphodiesterase inhibitor, and mimicked by the cAMP analogue N6,O2'-dibutyryl-adenosine 3',5'-cyclic-monophosphate (DBcAMP), the findings clearly indicate that hPTH was acting through the classic cAMP-mediated mechanism. Inasmuch as elevation of AP in growth plate chondrocytes coincides with MV formation, maturation and hypertrophy of the cells, and induction of mineralization, the stimulation of cell division and suppression of cellular AP indicates that hPTH would cause the cells to revert to a less differentiated state. Thus, elevation in PTH, which results from lowered circulating levels of Ca2+, should inhibit mineral deposition in the growth plate. This may be a physiological protective mechanism to prevent a further drain on serum Ca2+.

Effect of trifluoperazine and other drugs on matrix vesicle formation by chicken growth plate chondrocytes in primary cell culture.

Growth plate chondrocytes in primary culture release alkaline phosphatase (AP)-rich matrix vesicles (MV) into the culture medium. While these are thought to derive from the plasma membrane by a membrane fusion-dependent process, the mechanism is not fully understood. Recently, a cytosolic protein, synexin, has been shown to promote membrane fusion in a number of systems, and thus may be involved in MV formation. Since the action of synexin is selectively inhibited by trifluoperazine (TFP) and other phenothiazines, we examined the effects of these drugs, and imipramine, on cellular AP production and formation of AP-containing MV by cultured chondrocytes. In addition, we studied the effect on cell division, protein biosynthesis, and incorporation of palmitate into cellular and MV lipids. All of the drugs reduced cellular AP in a concentration-dependent manner; however, at the higher levels, chlorpromazine (CPZ) and TFP caused a transient sharp rise in MV AP activity. At IC50 levels, the drugs were more inhibitory to cellular AP than to MV AP, appearing to enhance significantly the transfer of available cellular AP into MV. In contrast, the drugs stimulated incorporation of [3H]palmitate into cellular lipids, but either had no effect on, or actually inhibited, incorporation of the fatty acid into MV. At these levels, the drugs had little effect on cell division and protein biosynthesis. The inhibitory effect of IC50 levels of CPZ on palmitate incorporation into MV appears to have resulted from impairment of vesicle formation per se, since at these levels the drug stimulated incorporation of the fatty acid into the cells. The transient stimulatory effect of higher levels of CPZ on MV AP levels, and the enhanced transfer of AP into MV by the drugs generally, may result from the effect of the drugs on membrane structure. Since TFP was not inhibitory to MV formation, it is doubtful that synexin was directly involved.

Effect of amino acid levels on matrix vesicle formation by epiphyseal growth plate chondrocytes in primary culture.

The effect of varying the amino acid concentrations of the culture medium on matrix vesicle formation was studied in primary cultures of chicken epiphyseal growth plate chondrocytes grown in Dulbecco's modified Eagle's medium (DME) supplemented with 10% fetal bovine serum (FBS). Decreasing the levels of free amino acids in the culture medium to levels of one-half, one quarter, and one eighth of the values normally present in DME caused a progressive decline in matrix vesicle (MV) formation. Increasing the level in the culture medium of those amino acids that are enriched in extracellular fluid (ECF) of growth plate cartilage significantly increased formation of matrix vesicles (MV), as assayed by the alkaline phosphatase (AP) activities present in high-speed sediments from spent culture media. However, adjusting the levels of all amino acids to match those of the ECF produced the greatest stimulation of MV formation. Of the amino acids that are notably enriched in ECF, glutamate (GLU), alanine (ALA), serine (SER), asparagine (ASN), and taurine (TAU) individually enhanced MV production, whereas proline (PRO), glycine (GLY), and aspartate (ASP) had essentially no effect. The simple combination of ECF levels of ALA and GLU resulted in a stimulation of MV formation equal to that observed when the eight aforementioned amino acids were elevated to ECF levels. Other combinations of ASP and GLY, or of TAU, SER, and ASN showed some stimulation, but at a lower level. Increasing the amino acid concentrations, alone or in combination, also increased the levels of cellular AP, and to a lesser extent cellular protein. While increases in cellular AP were generally correlated with increased formation of AP-rich MV, this was not uniformly true. These results indicate that in addition to hormones and growth factors, nutritional factors such as the levels of amino acids are also critical for normal phenotypic expression, growth, and matrix formation by epiphyseal chondrocytes.