Reproducibility and workability of the European test standard EN 12791 regarding the effectiveness of surgical hand antiseptics: a randomized, multicenter trial.

OBJECTIVES: To evaluate the reproducibility and workability of the in vivo test model of the European test standard EN 12791 regarding the effectiveness of surgical hand antiseptics and, as a secondary objective, to evaluate the power of the model to discriminate between the effectiveness of various formulations of surgical hand antiseptics. DESIGN: Prospective, randomized, multicenter study with a Latin square design. SETTING: Five laboratories at 2 universities, 2 disinfectant manufacturers, and 1 private testing institution. PARTICIPANTS: Twenty healthy adults in each laboratory. INTERVENTION: Surgical hand antisepsis was performed by scrubbing with chlorhexidine gluconate 4% detergent (CHG) or by rubbing the hands with propan-2-OL (70% by volume; Iso 70) or ethanol 85% (E 85); rubbing the hands and forearms for 3 minutes with propan-1-OL (N 60) was used as the reference disinfection procedure. We deliberately chose to use these antiseptics at the given concentrations because they were intended to cover the range of typical antiseptics submitted for approval according to EN 12791. METHODS: In once-weekly tests, the immediate effects of the 4 antiseptics were established according to the method laid down in EN 12791 by assessing the release of skin flora from the fingertips as viable bacteria counts per milliliter of sampling fluids before treatment and viable bacteria counts immediately after treatment, separately for both hands, such that after 4 weeks each volunteer had used every formulation once. RESULTS: The mean log reduction factor (RF) for the release of bacterial skin flora (the log RF was calculated as the log count before treatment minus the log count after treatment) and corresponding standard deviations for the 4 hand antisepsis formulations were as follows: for CHG, 1.1+/-0.3 colony-forming units (cfu) per milliliter of sampled fluid; for Iso 70, 1.7+/-0.3 cfu/mL; for E 85, 2.1+/-0.3 cfu/mL; and for N 60, 2.4+/-0.4 cfu/mL. The differences between these values proved significant (P<.001) by analysis of variance and in Tukey's "honestly significantly different" (HSD) post hoc test. Although, with regard to their immediate antibacterial activity, the same ranking of these antiseptics was found at all laboratories, the levels of efficacy were significantly different across laboratories (P<.001); no statistical difference was found between left and right hands (P>.01). Relating the log RF values of the other 3 formulations to those of the reference formulation (N 60) abolished differences between laboratories (P=.16); in addition, the interclass correlation coefficient decreased from 9.1% to 4.5%. With 20 volunteers, a minimum difference of 0.47 log between the mean log RFs of the reference formulation and an inferior test formulation will be detected as significant at an alpha of .05 (1-sided) and a 1- beta value of .8. CONCLUSION: The test method described in EN 12791 yielded the same conclusion on the effectiveness of the tested formulations in every laboratory and proved, therefore, reproducible and workable.     

Single-stage total C-2 intralesional spondylectomy for chordoma with three-column reconstruction. Technical note

Chordomas are locally invasive, malignant bone tumors that rarely occur in the cervical spine. En bloc resection or even fully resecting the tumor along its margin offers improved patient survival and a potential disease cure. Complete resection of tumors involving the upper cervical vertebrae requires a combined anterior-posterior approach but is complicated by the presence of vertebral arteries (VAs). In addition, reconstruction of the postresection defect may be prone to failure. The authors present a case of a chordoma involving the axis that was treated using a single-stage total intralesional C-2 spondylectomy with preservation of both VAs because the patient did not tolerate a preoperative occlusion test. A three-column reconstruction technique is also presented.     

Acute extracranial occlusion of the internal carotid artery: emergent surgery remains a viable option

Background

Acute symptomatic occlusion of extracranial internal carotid artery (eICA) can lead to a critical and potentially devastating stroke associated with high morbidity and mortality. Optimal treatment remains unclear. We analyzed our institutional experience with emergent surgical recanalization of acutely occluded eICA.

Methods

Retrospective analysis of hospital records, surgical reports, imaging studies and outpatient records. Final outcome was assessed according to modified Rankin Scale (mRS).

Results

Between January 2010 and September 2013, 22 patients underwent emergent surgical recanalization. There were 17 men and five women, mean age 65.4 years (range 37–85). Mean admission National Institute of Health Stroke Scale (NIHSS) was 12 (range 6–21). All patients had evidence of salvageable penumbra on perfusion computed tomography. Tandem intracranial lesion was present in nine patients. Surgical recanalization was successful in 16 patients (72.7 %). Twenty-four hours after surgery, 17 patients (77.2 %) improved by a minimum of 1 point on NIHSS, 14 patients (63.6 %) improved by three and more points; two patients deteriorated by two and five points, the latter treated initially with systemic thrombolysis due to intracranial hemorrhage. No other intracranial hematoma was observed. During 30 days following surgery, two patients died (9 % mortality rate) due to severity of initial stroke. On discharge, four patients were classified as mRS 0, five patients as mRS 1, five patients as mRS 2 and six patients as mRS 4. Favorable recovery (mRS 0–2) was achieved in 14 patients (63.6 %). No change in mRS was observed at three months.

Conclusions

Our results suggest that emergent surgical desobliteration of occluded eICA can lead to favorable recovery in a majority of patients. Patient selection based on penumbra imaging is crucial. Given the popularity and simplicity of carotid endarterectomy, the procedure should by no means be abandoned in the treatment of acute eICA occlusion.     

Evaluation of atezolizumab immunogenicity: Clinical pharmacology (part 1)

Baseline patient characteristics and prognostic factors are important considerations in oncology when evaluating the impact of immunogenicity on pharmacokinetics (PK) and efficacy. Here, we assessed the impact of anti‐drug antibodies (ADA) on the PK of the immune checkpoint inhibitor atezolizumab (an anti–PD‐L1 monoclonal antibody). We evaluated data from ≈ 4500 patients from 12 clinical trials across different tumor types, treatment settings, and dosing regimens. In our dataset, ~ 30% of patients (range, 13–54%) developed treatment‐emergent ADA, and in vitro neutralizing antibodies (NAb) were seen in ~ 50% of ADA‐positive (+) patients. Pooled time course data showed a trend toward lower atezolizumab exposure in ADA+ patients, which was more pronounced in ADA+/NAb+ patients. However, the atezolizumab concentration distributions overlapped, and drug concentrations exceeded 6 µg/ml, the target concentration required for receptor saturation, in greater than 95% of patients. Patients had sufficient exposure regardless of ADA status. The dose selected to allow for dosing over effects from ADA resulted in a flat exposure‐response relationship. Analysis of study results by ADA titer showed that exposure and overall survival were not affected in a clinically meaningful way. High tumor burden, low albumin, and high CRP at baseline showed the greatest association with ADA development but not with subsequent NAb development. These imbalanced factors at baseline can confound analysis of ADA impact. ADA increases atezolizumab clearance minimally (9%), and its impact on exposure based on the totality of the clinical pharmacology assessment does not appear to be clinically meaningful.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Anti‐drug antibodies (ADA) to anticancer therapeutics, including atezolizumab, might affect pharmacokinetics (PK) and drug efficacy.

• WHAT QUESTION DID THIS STUDY ADDRESS?

How do treatment‐emergent ADA impact atezolizumab exposure, and is there association between baseline prognostic factors and the development of ADA?

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

Based on a dataset of ~ 4500 patients, we showed that decreased atezolizumab exposure accompanying ADA and neutralizing ADA (NAb) development does not meaningfully impact drug concentrations required for receptor saturation. Further, differences in atezolizumab concentrations seen prior to ADA development demonstrated that baseline prognostic factor imbalances other than ADA can affect the drug exposure. Notably, baseline tumor burden, albumin, and C‐reactive protein can influence ADA development.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

The traditional approach of using univariate analysis to analyze PK or efficacy by ADA status alone may be inadequate, and confounding from baseline covariates should be considered or accounted for in ADA studies. The impacts of ADA on atezolizumab exposure are not expected to be clinically relevant.     

The intraoperative portable CT scanner-based spinal navigation: a viable option for instrumentation in the region of cervico-thoracic junction

Purpose

Innovative intraoperative imaging modalities open new horizons to more precise image acquisition and possibly to better results of spinal navigation. Planning of screw entry points and trajectories in this prospective study had been based on intraoperative imaging obtained by a portable 32-slice CT scanner. The authors evaluated accuracy and safety of this novel approach in the initial series of 18 instrumented surgeries in anatomically complex segment of cervico-thoracic junction.

Methods

We report on the single-institution results of assessment of anatomical accuracy of C5–T3 pedicle screw insertion as well as its clinical safety. The evaluation of total radiation dose and of time demands was secondary endpoint of the study.

Results

Out of 129 pedicle screws inserted in the segment of C5–T3, only 5 screws (3.9 %) did not meet the criteria for correct implant positioning. These screw misplacements had not been complicated by neural, vascular or visceral injury and surgeon was not forced to change the position intraoperatively or during the postoperative period. Quality of intraoperative CT imaging sufficient for navigation was obtained at all spinal segments regardless of patient´s habitus, positioning or comorbidity. A higher radiation exposition of the patient and 27 min longer operative time are consequences of this technique.

Conclusions

The intraoperative portable CT scanner-based spinal navigation is a reliable and safe method of pedicle screw insertion in cervico-thoracic junction.

     

Effects of alcohols, povidone-iodine and hydrogen peroxide on biofilms of Staphylococcus epidermidis

OBJECTIVES: To test the effects of several biocides [N-propanol, a commercially available propanol/ethanol/chlorhexidine mixture, polyvinylpyrolidone (povidone-iodine) and hydrogen peroxide] on established biofilms of Staphylococcus epidermidis isolated from patients with cardiac implant infections and catheter-related bacteraemia. METHODS: Biofilms were grown in microtitre plates for 24 h, dyed and stained with Crystal Violet. The mean optical density (OD) and the OD ratio (ODr=OD of the treated biofilm/OD of the untreated biofilm) were used for quantification. Biofilms were incubated with 60% (v/v) N-propanol, the mixture of propanol/ethanol/chlorhexidine, hydrogen peroxide at three concentrations (0.5%, 3% and 5%, v/v) and povidone-iodine for 1, 5, 15, 30 and 60 min. Unstained biofilms were sonicated and plated on Columbia agar for time-kill curves. S. epidermidis skin isolates from healthy volunteers were used as controls. RESULTS: Biofilm ODs of the clinical S. epidermidis isolates and the isolates from the healthy volunteers were significantly different (1.17+/-0.512 versus 0.559+/-0.095, respectively; mean+/-SD) (P<0.01). No viable S. epidermidis was detected in biofilms treated with the alcohols, N-propanol or the propanol/ethanol/chlorhexidine mixture. Incubation with povidone-iodine and hydrogen peroxide 3% and 5% led to a log reduction of the viable cells of >5 after incubation for 5 min, however, up to 10(3) viable cells were detected in four isolates after 30 min of incubation with povidone-iodine. CONCLUSIONS: S. epidermidis obtained from infected implants forms thicker biofilms than that of healthy volunteers. Hydrogen peroxide, at a concentration of 3% and 5%, and alcohols rapidly eradicate S. epidermidis biofilms, whereas povidone-iodine is less effective.     

CT-guided internal fixation of a hangman’s fracture

Most hangman’s fractures are treated conservatively. If surgery is indicated, an anterior approach using a C2/C3 graft and plate fusion is usually preferred. Another surgical method according to Judet is direct transpedicular osteosynthesis by the dorsal approach. This surgery is frequently rejected because of the high risk of spinal cord damage or vertebral artery tear. Direct transpedicular osteosynthesis of hangman’s fracture according to Judet is a “physiological operation” that does not cause fusion and creates anatomical conditions. This procedure enables appropriate reduction, compression of fragments and immediate stabilization of the C2 segment. A new aspect of Judet’s method of internal fixation of a hangman’s fracture is now proposed. Computed tomographic (CT) guidance is used to ensure safe and exact introduction of two screws from the posterior approach. This method of CT-guided internal fixation of hangman’s fracture allows, preoperatively, for an accurate assessment of the pattern and course of fracture line, selection of the anatomically safest screw path and determination of an appropriate screw length. The procedure also allows for accurate intraoperative control of instrument and implant placement, screw tightening, fracture reduction and anchoring of the screw tip in the contralateral cortex, using repeated CT scans. The procedure is performed in a CT unit under sterile conditions. This method was used in the treatment of eight male and two female patients aged 21–71 years. All treated patients were without neurological deficit. Follow-up ranged from 12 to 57 months (mean 33.3 months). No intraoperative or early or late postoperative complications were apparent. This new aspect of the surgical procedure ensures highly accurate screw placement and minimal risks, and fully achieves the “physiological” internal fixation. Received: 25 January 1999/Revised: 26 February 2000/Accepted: 23 March 2000