Contamination during production of heater-cooler units by Mycobacterium chimaera potential cause for invasive cardiovascular infections: results of an outbreak investigation in Germany, April 2015 to February 2016.

Invasive infections with Mycobacterium chimaera were reported in patients with previous open chest surgery and exposure to contaminated heater-cooler units (HCUs). We present results of the surveillance of clinical cases and of contaminated HCUs as well as environmental investigations in Germany up until February 2016. Clinical infections occurred in five male German cases over 50 years of age (range 53-80). Cases had been exposed to HCUs from one single manufacturer during open chest surgery up to five years prior to onset of symptoms. During environmental investigations, M. chimaera was detected in samples from used HCUs from three different countries and samples from new HCUs as well as in the environment at the manufacturing site of one manufacturer in Germany. Our investigation suggests that at least some of the M. chimaera infections may have been caused by contamination of HCUs at manufacturing site. We recommend that until sustainable measures for safe use of HCUs in operation theatres are implemented, users continue to adhere to instructions for use of HCUs and Field Safety Notices issued by the manufacturer, implement local monitoring for bacterial contamination and continuously check the websites of national and European authorities for current recommendations for the safe operation of HCUs.

Primary polydipsia: a case report.

Primary polydipsia (PP) is etiologically associated with physical factors and psychiatric disorders ("psychogenic polydipsia"). We present the case of a 28-year-old man with severe symptoms of polydipsia and polyuria. After a comprehensive physical assessment, the only finding was a lesion suggestive of pituitary microadenoma in the magnetic resonance imaging (MRI) scan of the brain. A thorough clinical and diagnostic assessment and the administration of a wide range of psychometric tools revealed no major psychiatric disorder apart from chronic anxiety and mild depressive symptoms. Our patient's PP symptoms might be associated with a dysfunction of the thirst center, which is located closely to the neuroanatomical lesion found in the MRI scan. Given that the underlying pathophysiology of PP remains, to a large extent, unclear, we emphasize on the difficulties to distinguish between PP's subtypes.

Genetic polymorphisms within tumor necrosis factor gene promoter region: a role for susceptibility to ventilator-associated pneumonia.

Debatable findings exist among various studies regarding the impact of single nucleotide polymorphisms (SNPs) within the promoter region of the tumor necrosis factor (TNF) gene for susceptibility to infections. Their impact was investigated in a cohort of mechanically ventilated patients who developed ventilator-associated pneumonia (VAP). Two-hundred and thirteen mechanically ventilated patients who developed VAP were enrolled. Genomic DNA was extracted and SNPs at the -376, -308 and -238 position of the promoter region of the TNF gene were assessed by restriction fragment length polymorphisms. Monocytes were isolated from 47 patients when they developed sepsis and stimulated by bacterial endotoxin for the production of TNFα and of interleukin-6 (IL-6). Patients were divided into two groups; 166 patients bearing only wild-type alleles of all three studied polymorphisms; and 47 patients carrying at least one A allele of the three studied SNPs. Time between start of mechanical ventilation and advent of VAP was significantly shorter in the second group than in the first group (log-rank: 4.416, p: 0.041). When VAP supervened, disease severity did not differ between groups. Stimulation of TNFα and of IL-6 was much greater by monocytes for patients carrying A alleles. Carriage of at least one A allele of the three studied SNPs at the promoter region of the TNF-gene is associated with shorter time to development of VAP but it is not associated with disease severity. Findings may be related with a role of the studied SNPs in the production of pro-inflammatory cytokines.

Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) detection in cancer patients: a prognostic marker for lung metastases from solid malignancies.

UNLABELLED: The aim of the study was to evaluate the serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) levels in breast, lung and colorectal cancer patients in correlation with clinical variables. PATIENTS AND METHODS: A total of 59 patients with a median age of 64 years and histologically confirmed breast 14, colorectal 15 or lung cancer 30 were evaluated. Five patients with breast cancer, 7 patients with colorectal cancer and 8 patients with lung cancer had lung metastases. Blood was collected upon enrolment, centrifuged and the serum kept at -80 degrees C until assayed for sTREM-1. The estimation of sTREM-1 was performed by a crude enzyme immunoabsorbent assay. RESULTS: High levels of sTREM-1 were observed in 50% of breast cancer, 33.3% of Small Cell Lung carcinoma (SCLC), 26.7% of colorectal cancer and 13.3% of Non Small Cell Lung Carcinoma (NSCLC) patients. sTREM-1 expression showed a correlation to the site of metastases. Higher concentrations were observed in the absence of lung metastases (p=0.019). DISCUSSION: The novel mediator sTREM-1 may be a prognostic marker for the detection of lung metastases in metastatic and locally advanced solid tumors.

Monocytes in systematic inflammatory response syndrome: differences between sepsis and acute pancreatitis.

AIM: To unravel the differences between systematic inflammatory response syndrome (SIRS) of acute pancreatitis compared to the same syndrome in sepsis. METHODS: Twenty-five patients were enrolled, 12 with sepsis and 13 acute pancreatitis. After diagnosis 20 mL blood was sampled. Half were assayed for isolation of monocytes and 10 mL was centrifuged for serum test of tumor necrosis factor alpha (TNFalpha and interleukin-6 (IL-6). Half of monocytes were incubated in the presence of patients' serum and supernatants were collected. The other half was treated for estimation of optical photometry under caspase-3 inhibition. TNFalpha and IL-6 were estimated by an enzyme immunoassay. RESULTS: median+/-SE of serum IL-6 in septic patients and acute pancreatitis patients was 192.30+/-35.40 ng/L and 21.00+/-16.05 ng/L, respectively (P<0.01). Respective values of caspase-3 were 0.94+/-0.17 pmol/min 10(4) cells and 0.34+/-0.09 pmol/min 10(4) cells (P<0.05). IL-6 of monocyte supernatants of patients with sepsis was significantly increased after addition of patients' serum, while that of patients with acute pancreatitis did not show significant difference. CONCLUSION: The data have shown that monocyte activity is different between acute pancreatitis and sepsis. This phenomenon might be explained as a different pathway to the pro-inflammatory cytokines release or could be a novel anti-inflammatory response in acute pancreatitis.

Monocytes as a site of production of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in the septic host.

The role of blood monocytes in the secretion of soluble triggering receptor expressed on myeloiod cells (sTREM-1) was studied in 90 patients with septic syndrome due to ventilator-associated pneumonia. Blood monocytes were isolated on 7 consecutive d after initiation of symptoms. Monocytes were incubated in the absence or presence of LPS and concentrations of sTREM-1 and TNFalpha in cell supernatants and serum were estimated by an enzyme-immunoassay. sTREM-1 and TNFalpha were consistently present at detectable levels in the cell supernatants. LPS induced increased levels of TNFalpha but not of sTREM-1. Supernatants recovered from monocytes on d 1 showed levels of sTREM-1 higher than those recovered on any of the following 6 d (p<0.05); these levels were higher in non-survivors than in survivors. Supernatants recovered from monocytes on d 1 of patients with severe sepsis had elevated concentrations of sTREM-1 compared to patients with septic shock and similar to patients with sepsis. A negative correlation was found between levels of sTREM-1 in the cell supernatants and the percentage of apoptotic monocytes. In essence, the above results suggest that monocytes contribute to the production of sTREM-1 in the event of septic syndrome.

Early apoptosis of blood monocytes in the septic host: is it a mechanism of protection in the event of septic shock?

INTRODUCTION: Based on the central role of the triggering of monocytes for the initiation of the septic cascade, it was investigated whether apoptosis of blood monocytes in septic patients is connected to their final outcome. METHODS: Blood monocytes were isolated from 90 patients with septic syndrome due to ventilator-associated pneumonia on days 1, 3, 5 and 7 from the initiation of symptoms. Apoptosis was defined after incubation with annexin-V-fluorescein isothiocyanate and propidium iodine and reading by a flow cytometer. The function of first-day monocytes was evaluated from the concentrations of tumour necrosis factor alpha (TNFalpha) and IL-6 in supernatants of cell cultures after triggering with endotoxins. TNFalpha, IL-6 and IL-8 were estimated in serum by an enzyme immunoassay. RESULTS: Mortality rates of patients with apoptosis < or =50% compared with patients with apoptosis >50% were 49.12% and 15.15%, respectively (P < 0.0001). Kaplan-Meier analysis showed a 28-day survival benefit in patients with septic shock and monocyte apoptosis >50% compared with those patients with apoptosis < or =50% (P = 0.0032). Production of IL-6 by monocytes on the first day by patients with apoptosis < or =50% was similar compared with monocytes isolated from healthy controls. Serum concentrations of TNFalpha were higher in patients with monocyte apoptosis < or =50% and septic shock compared with patients with apoptosis >50% on day 7; similar findings occurred for serum IL-6 on days 1 and 7 and for serum IL-8 on days 1 and 5. CONCLUSION: Early apoptosis of monocytes upon presentation of clinical signs of sepsis is connected to a favourable outcome. These findings are of particular importance for the patient with septic shock, where they might constitute a mechanism of pathogenesis.

Portal and systemic endotoxemia in abdominal operations: the significance of acute abdomen.

Little evidence is available for the implication of bacterial translocation in cases of acute abdomen. Intraoperative endotoxemia in both portal and systemic circulation was studied in 20 surgical patients with acute abdomen and in 36 controls undergoing elective abdominal surgery. Blood was sampled simultaneously from a mesenteric vein immediately after opening the peritoneum and from a peripheral vein. Endotoxin was measured by a colorimetric Limulus amebocyte lysate assay and malondialdehyde (MDA) was measured by the thiobarbiturate assay and passage through a high-performance liquid chromatography (HPLC) system as a marker of the oxidative status. LPS concentrations (mean +/- SE) in portal vein blood from patients with acute abdomen was 5.69 +/- 1.58 and from patients with chronic diseases 1.05 +/- 0.07 EU/ml (P < 0.0001). Respective values for the systemic circulation were 4.98 +/- 1.47 and 1.36 +/- 0.31 EU/ml (P < 0.0001). Concentrations of MDA (mean +/- SE) in portal vein blood from patients with acute abdomen was 11.16 +/- 4.00 and from patients with chronic diseases was 10.56 +/- 2.39 mum (P NS). Positive correlations were observed between endotoxin and MDA in both portal and systemic circulation. These results indicate increased levels of endotoxin in acute abdominal conditions pointing to the gut as the site of origin of the bacterial products.

Clarithromycin: immunomodulatory therapy of experimental sepsis and acute pyelonephritis by Escherichia coli.

The potency of clarithromycin as immunomodulator was assessed in an experimental model of sepsis based on acute pyelonephritis by susceptible Escherichia coli. 55 rabbits were utilized; 5 for preliminary pharmacokinetic study and 50 for treatment. The latter were divided into 5 groups of treatment, A: controls; B: clarithromycin pretreatment; C: amikacin pretreatment; D: clarithromycin treatment on presentation of pulmonary oedema; and E; amikacin treatment on presentation of pulmonary oedema. Survival was recorded; tumour necrosis factor-alpha (TNFalpha), and malondialdehyde (MDA) were estimated in serum; activities of caspase-3 in monocyte cytosolic extracts were studied; and bacterial counts made in various organs. Median survival of animals of groups A, B, C, D and E was 1.0, 21.0, 12.5, 2.0 and 5.0 d, respectively. TNFalpha and MDA and monocyte caspase-3 activity of group A increased over time; no increases were detected in groups B and C. Concentrations of MDA and activities of monocytic caspase-3 were decreased after administration of clarithromycin in group D, an effect not occurring in group E. Bacterial load was decreased in renal tissue of group D compared to group A. It is concluded that intravenous clarithromycin might constitute a promising immunomodulator in sepsis even in the advent of pulmonary oedema.