Thoracic organ transplantation may not increase the risk of bacterial transmission in intensive care units

A transmission study was performed to investigate whether organ recipients suffer more transmissions of bacteria than do non-transplanted patients. We chose enterococci for molecular typing because of their high prevalence, transmissibility, and predominance in causing nosocomial infections. Patients staying longer than 48h in a cardiovascular surgery intensive care unit (ICU) were included in our one-year prospective cohort study. Enterococci identified from clinical or surveillance isolates were collected and typed by PFGE. Episodes of transmission were defined by the identification of genetically indistinguishable isolates in two or more patients who were treated during overlapping intervals or within a 9-day window period in the same ICU. Risk factor analysis was performed. Out of 585 patients microbiological specimens were cultured from 336 patients. From 187 of these, enterococci were isolated. From 81 patients 186 enterococci isolates were typed. Out of 105 different enterococci strains, 16 cluster strains were detected and 30 episodes of transmissions occurred. The transmission rate was 7.8 per 1000 patient days. No significant association was found between "being cluster member "and "patient organ transplanted" (OR 1.5, CI(95%) 0.58; 3.98, p=0.38) or "patient treated in a single-room only" (OR 1.06, CI(95%) 0.36;3, 12, p=0.91), respectively. In contrast, "being cluster member" was associated with a prolonged length of stay (OR per additional days of stay 1.05, CI(95%) 1.01-1.09, p<0.01). Thoracic organ transplantation was not found to be a risk factor for bacterial transmission, but transmission was associated with a prolonged length of stay.     

Lipophilicity parameters for ionic liquid cations and their correlation to in vitro cytotoxicity

Regarding the great structural variability of the currently expanding group of ionic liquids, it is highly desirable to understand the basic factors affecting their toxicity in different biological systems. The present study of a set of 74 ionic liquids with imidazolium, pyrrolidinium, pyridinium, quinolinium, quaternary phosphonium and quaternary ammonium cations and the comparatively small anions Cl(-), Br(-), BF(4)(-), or PF(6)(-) demonstrates the influence of the cation lipophilicity on the cytotoxicity in IPC-81 leukemia cells from rats. The scope of this correlation is limited to ionic liquids with these or similarly small anions that are sufficiently nonreactive under physiological and chromatographic conditions and whose cation lipophilicity does not exceed a certain threshold.     

Bacterial contamination of multiple-dose vials: a prevalence study

BACKGROUND: Two patients died of a meningitis caused by Pseudomonas aeruginosa in a hospital in Germany in July 2001, their infections having been caused by a contaminated contrast media (iomeprol [Imeron]) used as a multiple-dose vial (MDV) over 8 days. Therefore, a prevalence study was performed to investigate the use and contamination of multiple-use vials in a tertiary hospital. METHODS: In a 1300-bed hospital on a specific day in November 2001, all used MDVs were collected by the infection control nurses. Information was recorded about the medication, labeling of vials, storing temperature, wards, and dates of opening. Each vial was also tested for sterility. RESULTS: Opened vials were to be found in all wards. Of the 227 vials available, 1 vial and 1 spike were contaminated with Staphylococcus epidermidis (contamination rate 0.9%; 95% CI, 0.3-2.1). The opening dates were marked on only 114 (50%) MDVs, 15 (13%) of which had already expired. Only 44 (19%) MDVs had been stored in the refrigerator, whereas 109 MDVs contained medications without any preserving agent. CONCLUSION: Results revealed somewhat risky handling of MDVs. In light of a possible high risk in this hospital of about 1 contaminated MDV per day, and in view of many reported outbreaks induced by contaminated MDVs, the following infection control measures were encouraged: alcohol hand hygiene, the disinfection of gums, observance of the manufacturer's recommendations, appropriate storing temperatures, marking the opening time, and avoiding the multiple use of medications not containing preserving agents.     

Acquired von Willebrand syndrome: experience from 2 years in a single laboratory compared with data from the literature and an international registry

Acquired von Willebrand syndrome (avWS) has gained more attention during the last years. An International Registry has been compared with the literature. It could be shown that the data collected from 123 publications compared well with the data from the registry, albeit with differences in the number of patients suffering from lymphoproliferative diseases and cardiovascular disorders, that were more prominent in the registry and the group of miscellaneous conditions underrepresented in the registry. Our data are clearly different for the lymphoproliferative diseases with only four patients in 2 years. These patients usually suffer from severe bleeding complications together with low to very low factor VIII/von Willebrand factor (FVIII/vWF) concentrations and thus will not go undiagnosed. In contrast to this, patients with cardiovascular disorders usually bleed only during surgical procedures or catheter procedures. At that time they have increased vWF parameters. Because of this and because the acute bleeding is of limited duration and usually not life threatening, many of them are discharged without a proper diagnosis and are only rarely referred to a specialized diagnostic work-up thereafter. In conclusion, avWS, although not a frequent disease, is nevertheless clearly underdiagnosed. This should be addressed in future prospective studies.     

Mechanoenzymatics of titin kinase

Biological responses to mechanical stress require strain-sensing molecules, whose mechanically induced conformational changes are relayed to signaling cascades mediating changes in cell and tissue properties. In vertebrate muscle, the giant elastic protein titin is involved in strain sensing via its C-terminal kinase domain (TK) at the sarcomeric M-band and contributes to the adaptation of muscle in response to changes in mechanical strain. TK is regulated in a unique dual autoinhibition mechanism by a C-terminal regulatory tail, blocking the ATP binding site, and tyrosine autoinhibition of the catalytic base. For access to the ATP binding site and phosphorylation of the autoinhibitory tyrosine, the C-terminal autoinhibitory tail needs to be removed. Here, we use AFM-based single-molecule force spectroscopy, molecular dynamics simulations, and enzymatics to study the conformational changes during strain-induced activation of human TK. We show that mechanical strain activates ATP binding before unfolding of the structural titin domains, and that TK can thus act as a biological force sensor. Furthermore, we identify the steps in which the autoinhibition of TK is mechanically relieved at low forces, leading to binding of the cosubstrate ATP and priming the enzyme for subsequent autophosphorylation and substrate turnover.     

Predictors for clinically relevant Gleason score upgrade in patients undergoing radical prostatectomy

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Clinically relevant GSU in the prostatectomy specimen is a common phenomenon. Clinically relevant GSU occurs in one of three patients with clinically ‘very’ low‐risk PCa, and a low number of biopsy cores is the key negative predictor.

OBJECTIVE

? To evaluate clinical predictors for Gleason score upgrade (GSU) in radical prostatectomy (RP) specimen, especially in patients with ‘very’ low risk PCA (T1c and biopsy Gleason score ≤6 and PSA <10 ng/ml and ≤2 positive biopsy cores and PSA density <0.15).

Patients and Methods

? 402 consecutive patients undergoing RP between 2004 and 2006, including a subgroup of 62 patients with ‘very’ low risk PCA, were examined. ? Patients were categorized for clinically relevant GSU (defined as upgrade into a higher PCA risk category). ? Parameters including number of biopsy cores obtained, positive biopsy cores, prostate weight, PSA, DRE and pathology department were evaluated for their role as predictors. ? Furthermore, GSU in RP specimen was analyzed for its impact on pT‐stage.

RESULTS

? Clinically relevant GSU occurred in 38.1% in the whole cohort and in 32.3% in the ‘very’ low risk PCA subgroup. Gleason score downgrade (GSD) occurred in 4.7%. ? Number of biopsy cores obtained and prostate weight were independent negative predictors of GSU in all 402 patients (P = 0.02 and P = 0.03, respectively). ? In the ‘very’ low risk group, only number of biopsy cores obtained revealed as an independent negative predictor of GSU (P = 0.02). ? PSA, DRE, number of positive cores or pathology department were not associated to GSU. ? In the ‘very’ low risk group, GSU was related with extracapsular tumor extension (P = 0.05).

Conclusions

? Clinically relevant GSU in RP specimen is still a challenging problem. ? Increasing the number of biopsy cores lower this risk significantly. GSD is rare and thus of minor importance for treatment decisions.