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ABSTRACT: Background:The specific morphological and biomechanical characteristics of the osteochondral unit of the ankle joint are not yet fully understood. This anatomical study aimed to map regional thickness of the articular hyaline uncalcified cartilage and its adjacent layers of mineralized cartilage and subchondral bone as well as to measure the regional indentation stiffness of human ankle joint cartilage.Materials and Methods:A total of 20 pairs of human cadaver ankle joints (median age: 78 years) were evaluated by histomorphometry and multidetector row double-contrast CT arthrography for cartilage thickness in 17 distinct anatomical regions. In addition, regional distribution of the subchondral bone plate and of the mineralized cartilage was scrutinized histologically. Cartilage indentation stiffness was measured using an arthroscopic handheld device (Artscan200), especially validated for use in thin cartilage. The correlation between the thickness of different components of the osteochondral unit and the cartilage indentation stiffness was evaluated.Results:The thinnest uncalcified cartilage was measured at the anterior talar dome and the distal fibula. The thickest uncalcified cartilage was found in the mid and posterior talar dome, as well as in the tibial plafond. Mineralized cartilage and subchondral bone showed highest values at the anteromedial talar dome. Cartilage indentation stiffness showed a bicentric distribution pattern in 14/20 ankle pairs and was highest in regions with thin cartilage. Positive correlation between the thickness of the mineralized cartilage and the subchondral bone plate was found. No correlation between the thickness of the uncalcified and the mineralized cartilage could be identified.Conclusion:This anatomical study provides a comprehensive mapping of the osteochondral unit of the human ankle joint in elderly people. Articular hyaline uncalcified cartilage and the subchondral bone plate showed clear regional differences and were reciprocally distributed. Cartilage indentation stiffness was inversely correlated to cartilage thickness in elderly people.Clinical Relevance:Thorough understanding of the osteochondral unit of the ankle joint could be helpful for clinicians and researchers in the development of improved operative repair techniques for osteochondral defects in the ankle joint, for example, in constructing specific tissue-engineered osteochondral plugs.
The Foot and Ankle Online Journal 02/2013; · 1.22 Impact Factor
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ABSTRACT: BACKGROUND: A large number of parameters are registered by pedobarography, usually requiring a research setting for interpretation. The purpose of this study was to evaluate which pedobarographic parameters (adjusted for walking speed and body weight) discriminate between healthy volunteers and patients after ankle or tibiotalocalcaneal arthrodesis. Furthermore, we evaluated which parameters are associated with the American Orthopaedic Foot and Ankle Society (AOFAS) score. METHODS: Thirty-five healthy volunteers, 57 patients with ankle and 42 with tibiotalocalcaneal arthrodesis were assessed by AOFAS scores and dynamic pedobarography. The arthrodesis patients were further investigated with radiographs. Median follow up was 4years. Eighteen basic parameters were measured each in the hind-, mid-, and forefoot. For dimension reduction, we represented a pre-selected set of 9 parameters by two indices (load, rollover). We used ordinal logistic and multiple linear regression to address the questions. FINDINGS: The midfoot index of load was the most important pedobarographic predictor (interquartile range odds ratio 100; 95% confidence interval 13, 771) for belonging to the healthy volunteers rather than the ankle or tibiotalocalcaneal arthrodesis groups. Similarly, it was an independent predictor for the AOFAS score (interquartile range effect 5 points; 95% confidence interval 1, 9). Healthy volunteers had a deeper midfoot depression in the force/pressure time graphs compared to patients after arthrodesis. INTERPRETATION: When evaluating foot function after ankle or tibiotalocalcaneal arthrodesis, the interpretation of a large number of pedobarographic parameters can be reduced to the interpretation of the midfoot index of load and the evaluation of the force/pressure time graphs.
Clinical biomechanics (Bristol, Avon) 09/2012; · 1.76 Impact Factor
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ABSTRACT: To evaluate the feasibility of implementation of the refined window for routine antimicrobial prophylaxis (RAP) of 30-74 minutes before skin incision compared to the World Health Organization (WHO) standard of 0-60 minutes.
Prospective study on timing of routine antimicrobial prophylaxis in 2 different time periods.
Tertiary referral university hospital with 30,000 surgical procedures per year.
In all consecutive vascular, visceral, and trauma procedures, the timing was prospectively recorded during a first time period of 2 years (A; baseline) and a second period of 1 year (B; after intervention). An intensive intervention program was initiated after baseline. The primary outcome parameter was timing; the secondary outcome parameter was surgical site infection (SSI) rate in the subgroup of patients undergoing cholecystectomy/colon resection.
During baseline time period A (3,836 procedures), RAP was administered 30-74 minutes before skin incision in 1,750 (41.0%) procedures; during time period B (1,537 procedures), it was administered in 914 (56.0%; [Formula: see text]). The subgroup analysis did not reveal a significant difference in SSI rate.
This bundle of interventions resulted in a statistically significant improvement of timing of RAP even at a shortened window compared to the WHO standard.
Infection Control and Hospital Epidemiology 09/2012; 33(9):912-6. · 3.67 Impact Factor
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ABSTRACT: BACKGROUND: Surgeons' personalities have been described as different from those of the general population, but this was based on small descriptive studies limited by the choice of evaluation instrument. Furthermore, although the importance of the human factor in team performance has been recognized, the effect of personality traits on technical performance is unknown. This study aimed to compare surgical residents' personality traits with those of the general population and to evaluate whether an association exists between their personality traits and technical performance using a virtual reality (VR) laparoscopy simulator. METHODS: In this study, 95 participants (54 residents with basic, 29 with intermediate laparoscopic experience, and 12 students) underwent personality assessment using the NEO-Five Factor Inventory and performed five VR tasks of the Lap Mentor™ basic tasks module. The residents' personality traits were compared with those of the general population, and the association between VR performance and personality traits was investigated. RESULTS: Surgical residents showed personality traits different from those of the general population, demonstrating lower neuroticism, higher extraversion and conscientiousness, and male residents showed greater openness. In the multivariable analysis, adjusted for gender and surgical experience, none of the personality traits was found to be an independent predictor of technical performance. CONCLUSIONS: Surgical residents present distinct personality traits that differ from those of the general population. These traits were not found to be associated with technical performance in a virtual environment. The traits may, however, play an important role in team performance, which in turn is highly relevant for optimal surgical performance.
Surgical Endoscopy 06/2012; · 4.01 Impact Factor
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ABSTRACT: BackgroundThe use of virtual reality (VR) has gained increasing interest to acquire laparoscopic skills outside the operating theatre
and thus increasing patients' safety. The aim of this study was to evaluate trainees' acceptance of VR for assessment and
training during a skills course and at their institution.
MethodsAll 735 surgical trainees of the International Gastrointestinal Surgery Workshop 2006–2008, held in Davos, Switzerland, were
given a minimum of 45 minutes for VR training during the course. Participants' opinion on VR was analyzed with a standardized
questionnaire.
ResultsFivehundred-twenty-seven participants (72%) from 28 countries attended the VR sessions and answered the questionnaires. The
possibility of using VR at the course was estimated as excellent or good in 68%, useful in 21%, reasonable in 9% and unsuitable
or useless in 2%. If such VR simulators were available at their institution, most course participants would train at least
one hour per week (46%), two or more hours (42%) and only 12% wouldn't use VR. Similarly, 63% of the participants would accept
to operate on patients only after VR training and 55% to have VR as part of their assessment.
ConclusionResidents accept and appreciate VR simulation for surgical assessment and training. The majority of the trainees are motivated
to regularly spend time for VR training if accessible.
Patient Safety in Surgery 04/2012; 2(1):1-7.
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ABSTRACT: The optimal timing of elective surgery in diverticulitis remains unclear. We attempted to investigate early elective versus late elective laparoscopic surgery in acute recurrent diverticulitis in a retrospective study.
Data of patients undergoing elective laparoscopic surgery for diverticulitis were retrospectively gathered, including Hinchey stages I-II a/b. the primary endpoint was in-hospital complications according to the Clavien-Dindo classification. Secondary endpoints were surgical complications, operative time, conversion rate, and length of hospital stay.
Of 237 patients, 81 (34%) underwent early elective operation (group A) and 156 (66%) underwent late elective operation (group B). In-hospital complications developed in 32% in group A and in 34% in group B (risk difference 2%, 95% Confidence Interval (95% CI): -11%, 14%). Higher age (p = 0.048) and borderline higher American Society of Anesthesiologists score (p = 0.056) were risk factors for in-hospital complications. Severe surgical complications occurred in 9% of patients in group A and 10% in group B (risk difference 2%, 95% CI: -6%, 9%). Conversion rate was 9% in group A and 3% in group B (p = 0.070). Severity of disease did not seem to have an impact on complications or length of hospital stay. The median postoperative hospital stay was 8 days in both groups (interquartile range 6-10). Mean operative time was 220 min (SD 64) in group A and 202 min (SD 48) in group B.
This is the first study comparing early versus late elective surgery for diverticulitis in terms of the postoperative outcome using a validated classification. Although the retrospective setting and large confidence intervals don't allow definitive recommendations, these results are of utmost importance for the design of future prospective, randomized controlled trials.
World Journal of Surgery 02/2012; 36(4):898-907. · 2.36 Impact Factor
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ABSTRACT: Surgical residents often use a laparoscopic camera in minimally invasive surgery for the first time in the operating room (OR) with no previous education or experience. Computer-based simulator training is increasingly used in residency programs. However, no randomized controlled study has compared the effect of simulator-based versus the traditional OR-based training of camera navigation skills.
This prospective randomized controlled study included 24 pregraduation medical students without any experience in camera navigation or simulators. After a baseline camera navigation test in the OR, participants were randomized to six structured simulator-based training sessions in the skills lab (SL group) or to the traditional training in the OR navigating the camera during six laparoscopic interventions (OR group). After training, the camera test was repeated. Videos of all tests (including of 14 experts) were rated by five blinded, independent experts according to a structured protocol.
The groups were well randomized and comparable. Both training groups significantly improved their camera navigational skills in regard to time to completion of the camera test (SL P = 0.049; OR P = 0.02) and correct organ visualization (P = 0.04; P = 0.03). Horizon alignment improved without reaching statistical significance (P = 0.20; P = 0.09). Although both groups spent an equal amount of actual time on camera navigation training (217 vs. 272 min, P = 0.20), the SL group spent significantly less overall time in the skill lab than the OR group spent in the operating room (302 vs. 1002 min, P < 0.01).
This is the first prospective randomized controlled study indicating that simulator-based training of camera navigation can be transferred to the OR using the traditional hands-on training as controls. In addition, simulator camera navigation training for laparoscopic surgery is as effective but more time efficient than traditional teaching.
Surgical Endoscopy 08/2011; 26(1):235-41. · 4.01 Impact Factor
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ABSTRACT: In children, video game experience improves spatial performance, a predictor of surgical performance. This study aims at comparing laparoscopic virtual reality (VR) task performance of children with different levels of experience in video games and residents.
A total of 32 children (8.4 to 12.1 years), 20 residents, and 14 board-certified surgeons (total n = 66) performed several VR and 2 conventional tasks (cube/spatial and pegboard/fine motor). Performance between the groups was compared (primary outcome). VR performance was correlated with conventional task performance (secondary outcome).
Lowest VR performance was found in children with low video game experience, followed by those with high video game experience, residents, and board-certified surgeons. VR performance correlated well with the spatial test and moderately with the fine motor test.
The use of computer games can be considered not only as pure entertainment but may also contribute to the development of skills relevant for adequate performance in VR laparoscopic tasks. Spatial skills are relevant for VR laparoscopic task performance.
Surgical Innovation 01/2011; 18(2):160-70. · 2.13 Impact Factor
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ABSTRACT: The type of surgical antimicrobial prophylaxis (SAP) is determined by the spectrum and antimicrobial resistance of pathogens causing surgical site infections (SSI). The aim of this study was to define the microbiological features of SSI in general surgery patients at Basel University Hospital in order to validate our current strategy of single-shot SAP with 1.5 g cefuroxime (plus 500 mg metronidazole in colorectal surgery).
A prospective observational cohort of consecutive vascular, visceral and trauma procedures was analysed to evaluate the incidence of SSI. Surgical wounds and resulting infections were assessed to centres for disease control standards. Microbiological evaluation was performed by microscopic direct preparation, cultures and testing for antibiotic resistance.
A total of 293 instances of SSI were detected in this cohort of 6283 surgical procedures (4.7%). Microbiological species were identified in 129 of 293 SSI (44%). Staphylococcus aureus (29.5%) was the most common pathogen causing SSI in trauma and vascular surgery, whereas Escherichia coli (20.9%) was more frequently responsible for SSI in visceral surgery. Importantly, not a single case of SSI was caused by antimicrobial-resistant pathogens in this series.
The spectrum of pathogens causing SSI identified and the very low incidence of antimicrobial resistance at Basel University Hospital validate the continuous use of single-shot single-drug SAP with cefuroxime (plus metronidazole in colorectal surgery).
Schweizerische medizinische Wochenschrift 01/2011; 140:w13146. · 1.68 Impact Factor
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ABSTRACT: The aim of the present study was to investigate whether trainees' performance on a virtual reality angled laparoscope navigation task correlates with scores obtained on a validated conventional test of spatial ability. 56 participants of a surgery workshop performed an angled laparoscope navigation task on the Xitact LS 500 virtual reality Simulator. Performance parameters were correlated with the score of a validated paper-and-pencil test of spatial ability. Performance at the conventional spatial ability test significantly correlated with performance at the virtual reality task for overall task score (p < 0.001), task completion time (p < 0.001) and economy of movement (p = 0.035), not for endoscope travel speed (p = 0.947). In conclusion, trainees' performance in a standardized virtual reality camera navigation task correlates with their innate spatial ability. This VR session holds potential to serve as an assessment tool for trainees.
Indian Journal of Surgery 08/2010; 72(4):327-30. · 0.08 Impact Factor
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Michel Adamina, Rachel Rosenthal,
Walter P Weber,
Daniel M Frey,
Carsten T Viehl,
Martin Bolli,
Rolf W Huegli,
Augustinus L Jacob,
Michael Heberer,
Daniel Oertli,
Walter Marti,
Giulio C Spagnoli,
Paul Zajac
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ABSTRACT: Recombinant vaccinia virus (rVV) encoding tumor-associated antigens (TAAs) and adhesion or costimulatory molecules may represent important immunogenic reagents for cancer immunotherapy. Recently, intranodal (IN) antigen administration was suggested to be more immunogenic than intradermal (ID) vaccination. However, IN rVV administration has not been attempted so far. We used a rVV encoding gp100(280-288), Melan-A/MART-1(27-35) and tyrosinase(1-9) HLA-A0201 restricted epitopes and CD80 and CD86 costimulatory molecules in stage III and IV melanoma patients in a phase 1/2 trial. Of 15 patients initiating treatment, including two cycles of IN immunization, each comprising one rVV administration and three recall injections of the corresponding peptides, accompanied by subcutaneous granulocyte macrophage-colony stimulating factor supplementation, five withdrew due to progressing disease. Of 10 remaining patients seven showed evidence of induction of cytotoxic T lymphocytes (CTLs) directed against at least one epitope under investigation, as detectable by limiting dilution analysis (LDA) of specific precursors and multimer staining. Adverse reactions were mild (National Cancer Institute (NCI) grade 1-2) and mainly represented by fever, skin rashes, and pruritus. These data indicate that IN administration of rVV encoding melanoma-associated epitopes and costimulatory molecules is safe and immunogenic.
Molecular Therapy 11/2009; 18(3):651-9. · 6.87 Impact Factor
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ABSTRACT: Clinically apparent surgical glove perforation increases the risk of surgical site infection (SSI).
Prospective observational cohort study.
University Hospital Basel, with an average of 28,000 surgical interventions per year.
Consecutive series of 4147 surgical procedures performed in the Visceral Surgery, Vascular Surgery, and Traumatology divisions of the Department of General Surgery.
The outcome of interest was SSI occurrence as assessed pursuant to the Centers of Disease Control and Prevention standards. The primary predictor variable was compromised asepsis due to glove perforation.
The overall SSI rate was 4.5% (188 of 4147 procedures). Univariate logistic regression analysis showed a higher likelihood of SSI in procedures in which gloves were perforated compared with interventions with maintained asepsis (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.4-2.8; P < .001). However, multivariate logistic regression analyses showed that the increase in SSI risk with perforated gloves was different for procedures with vs those without surgical antimicrobial prophylaxis (test for effect modification, P = .005). Without antimicrobial prophylaxis, glove perforation entailed significantly higher odds of SSI compared with the reference group with no breach of asepsis (adjusted OR, 4.2; 95% CI, 1.7-10.8; P = .003). On the contrary, when surgical antimicrobial prophylaxis was applied, the likelihood of SSI was not significantly higher for operations in which gloves were punctured (adjusted OR, 1.3; 95% CI, 0.9-1.9; P = .26).
Without surgical antimicrobial prophylaxis, glove perforation increases the risk of SSI.
Archives of surgery (Chicago, Ill.: 1960) 07/2009; 144(6):553-8; discussion 558. · 4.32 Impact Factor
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ABSTRACT: The purpose of the study was to investigate allogeneic blood transfusion (ABT) and preoperative anemia as risk factors for surgical site infection (SSI).
A prospective, observational cohort of 5873 consecutive general surgical procedures at Basel University Hospital was analyzed to determine the relationship between perioperative ABT and preoperative anemia and the incidence of SSI. ABT was defined as transfusion of leukoreduced red blood cells during surgery and anemia as hemoglobin concentration of less than 120 g/L before surgery. Surgical wounds and resulting infections were assessed to Centers for Disease Control standards.
The overall SSI rate was 4.8% (284 of 5873). In univariable logistic regression analyses, perioperative ABT (crude odds ratio [OR], 2.93; 95% confidence interval [CI], 2.1 to 4.0; p < 0.001) and preoperative anemia (crude OR, 1.32; 95% CI, 1.0 to 1.7; p = 0.037) were significantly associated with an increased odds of SSI. After adjusting for 13 characteristics of the patient and the procedure in multivariable analyses, associations were substantially reduced for ABT (OR, 1.25; 95% CI, 0.8 to 1.9; p = 0.310; OR, 1.07; 95% CI, 0.6 to 2.0; p = 0.817 for 1-2 blood units and >or=3 blood units, respectively) and anemia (OR, 0.91; 95% CI, 0.7 to 1.2; p = 0.530). Duration of surgery was the main confounding variable.
Our findings point to important confounding factors and strengthen existing doubts on leukoreduced ABT during general surgery and preoperative anemia as risk factors for SSIs.
Transfusion 06/2009; 49(9):1964-70. · 3.22 Impact Factor
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ABSTRACT: Despite availability of other training forms, tutorial assistance cannot be entirely replaced in surgical education. Concerns exist that tutorial assistance may lead to an increased rate of surgical site infection (SSI). The purpose of the present study was to investigate whether the risk of SSI is higher after surgery with tutorial assistance than after surgery performed autonomously by a fully trained surgeon.
All consecutive visceral, vascular, and traumatological inpatient procedures at a Swiss University Hospital were prospectively recorded during a 24-month period, and the patients were followed for 12 months to ascertain the occurrence of SSI. Using univariable and multivariable logistic regressions, we assessed the association of tutorial assistance surgery with SSI in 6,103 interventions.
Autonomously performed surgery was associated with SSI in univariable analysis (5.36% SSI vs. 3.81% for tutorial assistance, p = 0.006). In multivariable analysis, the odds of SSI for tutorial assistance was no longer significantly lower (Odds Ratio [OR] = 0.82; 95% Confidence Interval [CI]: 0.62-1.09; p = 0.163).
Surgical training does not lead to higher SSI rate if trainees are adequately supervised and interventions are carefully selected. Although other forms of training are useful, tutorial assistance in the operating room continues to be the mainstay of surgical education.
World Journal of Surgery 05/2009; 33(6):1165-73. · 2.36 Impact Factor
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Rachel Rosenthal,
Célia Groeper,
Laura Bracci,
Michel Adamina,
Chantal Feder-Mengus,
Paul Zajac,
Giandomenica Iezzi,
Martin Bolli,
Walter P. Weber,
Daniel M. Frey,
Urs von Holzen,
Daniel Oertli,
Michael Heberer,
Giulio C. Spagnoli
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ABSTRACT: Common receptor γ chain (c-γ) cytokines (CKs) support proliferation of CD8+ T cells in presence or absence of antigen triggering and help maintaining the immunologic memory. We addressed the effects of low (≤5 ng/mL)-dose interleukin (IL)-2, IL-7, or IL-15 on human naive and memory antigen-specific CD8+ T cells. Peripheral blood CD8+ lymphocytes proliferated with decreasing efficiency in response to IL-15, IL-7, and IL-2. Of note, IL-15 preferentially promoted expansion of CD45RA-/CD8+ T-cell memory subset. Accordingly, cytotoxic T lymphocytes specific for cytomegalovirus-derived antigens from seropositive donors proliferated in response to IL-15 and, to lesser extent to IL-7, but poorly to IL-2. CD8+ T cells were then pretreated with CK before antigen stimulation using, as read out, specific cytotoxic activity. After the pretreatment with IL-15, but not IL-2, previously experienced viral antigens induced vigorous cytotoxic responses. Minor effects of IL-7 were also detectable. In contrast, IL-2 best supported the cytotoxic T lymphocyte generation from prevailingly naive CD8+ T cells from HLA-A*0201+ healthy donors, specific for L27Melan-A/MART-126-35 melanoma-associated antigen. Cells from melanoma patients were tested before and after Melan-A/MART-1-targeted antigen-specific immunotherapy. Untreated patients showed heterogeneous patterns of responsiveness to c-γ CK. However, when naive patients whose CD8+ T cells best responded to IL-2 were vaccinated, a modified responsiveness pattern was detectable. After immunization, cells displayed a significantly higher response to IL-15 than to IL-2 pretreatment. Thus, responsiveness to c-γ CK is critically influenced by naive or memory status of peripheral blood CD8+ T cells.
Journla of Immunotherapy 03/2009; 32(3):252-261. · 3.27 Impact Factor
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Journal of the American College of Surgeons 08/2008; 207(1):95-105. · 4.55 Impact Factor
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ABSTRACT: To quantify the economic burden of in-hospital surgical site infections (SSIs) at a European university hospital.
Matched case-control study nested in a prospective observational cohort study.
Basel University Hospital in Switzerland, where an average of 28,000 surgical procedures are performed per year.
All in-hospital occurrences of SSI associated with surgeries performed between January 1, 2000, and December 31, 2001, by the visceral, vascular, and traumatology divisions at Basel University Hospital were prospectively recorded. Each case patient was matched to a control patient by age, procedure code, and National Nosocomial Infection Surveillance System risk index. The case-control pairs were analyzed for differences in cost of hospital care and in provision of specialized care.
A total of 6,283 procedures were performed: 187 SSIs were detected in inpatients, 168 of whom were successfully matched with a control patient. For case patients, the mean additional hospital cost was SwF-19,638 (95% confidence interval [CI], SwF-8,492-SwF-30,784); the mean additional postoperative length of hospital stay was 16.8 days (95% CI, 13-20.6 days); and the mean additional in-hospital duration of antibiotic therapy was 7.4 days (95% CI, 5.1-9.6 days). Differences were primarily attributable to organ space SSIs (n = 76).
In a European university hospital setting, SSIs are costly and constitute a heavy and potentially preventable burden on both patients and healthcare providers.
Infection Control and Hospital Epidemiology 08/2008; 29(7):623-9. · 3.67 Impact Factor
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Laura Bracci,
Reto Schumacher,
Maurizio Provenzano,
Michel Adamina, Rachel Rosenthal,
Celia Groeper,
Paul Zajac,
Giandomenica Iezzi,
Enrico Proietti,
Filippo Belardelli,
Giulio C Spagnoli
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ABSTRACT: Dendritic cells (DC) can be activated by proinflammatory cytokines or upon toll-like receptor (TLR) triggering. These stimuli induce specific patterns of phenotypic modulation and gene expression profiles. We investigated whether TLR triggering represents an indispensable requirement for the induction of T cell responses by human DC generated upon culture of monocytes in the presence of granulocyte macrophage colony-stimulating factor and interferon-alpha (IFN-DC). As model stimulator we chose imidazoquinolone (3M-001), a synthetic TLR7 agonist used in the treatment of skin infections and tumors and as experimental adjuvant. At difference with DC generated upon culture of monocytes in the presence of granulocyte macrophage colony-stimulating factor and interleukin (IL-4) (IL-4-DC), IFN-DC display a semimature phenotype. Furthermore, IFN-DC, but not IL-4-DC are able to induce CD4+ and CD8+ T cell responses, in steady state, for example, in the absence of TLR triggering. 3M-001 treatment induces up-regulation of the surface expression of costimulatory molecules and "de novo" production of IL-12 and IL-6 in IFN-DC. However, TLR7 triggering fails to significantly enhance the capacity of IFN-DC to induce antigen-specific cytotoxic T lymphocytes and to stimulate allogeneic CD4+ T cells. These data indicate that TLR engagement and IL-12 production do not represent indispensable prerequisites for optimal antigen-presenting cell function in IFN-DC, qualifying these cells as powerful cellular reagents of potential use in active specific immunotherapy.
Journla of Immunotherapy 07/2008; 31(5):466-74. · 3.27 Impact Factor
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Walter P Weber,
Walter R Marti,
Marcel Zwahlen,
Heidi Misteli, Rachel Rosenthal,
Stefan Reck,
Philipp Fueglistaler,
Martin Bolli,
Andrej Trampuz,
Daniel Oertli,
Andreas F Widmer
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ABSTRACT: To obtain precise information on the optimal time window for surgical antimicrobial prophylaxis.
Although perioperative antimicrobial prophylaxis is a well-established strategy for reducing the risk of surgical site infections (SSI), the optimal timing for this procedure has yet to be precisely determined. Under today's recommendations, antibiotics may be administered within the final 2 hours before skin incision, ideally as close to incision time as possible.
In this prospective observational cohort study at Basel University Hospital we analyzed the incidence of SSI by the timing of antimicrobial prophylaxis in a consecutive series of 3836 surgical procedures. Surgical wounds and resulting infections were assessed to Centers for Disease Control and Prevention standards. Antimicrobial prophylaxis consisted in single-shot administration of 1.5 g of cefuroxime (plus 500 mg of metronidazole in colorectal surgery).
The overall SSI rate was 4.7% (180 of 3836). In 49% of all procedures antimicrobial prophylaxis was administered within the final half hour. Multivariable logistic regression analyses showed a significant increase in the odds of SSI when antimicrobial prophylaxis was administered less than 30 minutes (crude odds ratio = 2.01; adjusted odds ratio = 1.95; 95% confidence interval, 1.4-2.8; P < 0.001) and 120 to 60 minutes (crude odds ratio = 1.75; adjusted odds ratio = 1.74; 95% confidence interval, 1.0-2.9; P = 0.035) as compared with the reference interval of 59 to 30 minutes before incision.
When cefuroxime is used as a prophylactic antibiotic, administration 59 to 30 minutes before incision is more effective than administration during the last half hour.
Annals of surgery 06/2008; 247(6):918-26. · 7.90 Impact Factor
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Michel Adamina,
Walter P Weber, Rachel Rosenthal,
Reto Schumacher,
Paul Zajac,
Ulrich Guller,
Daniel M Frey,
Daniel Oertli,
Markus Zuber,
Michael Heberer,
Giulio C Spagnoli
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ABSTRACT: To the exception of early stages of disease, the morbidity and mortality of melanoma is considerable, with no acknowledged therapeutic options beyond surgery. Immunotherapy of melanoma has achieved some success, but further refinements are urgently needed in order to realize its potential. This paper describes a multi-centre phase I/II open labeled, controlled clinical trial investigating 2 innovative immunotherapeutic reagents. Two successive groups of 20 resected AJCC stages IIb-IV melanoma patients will be treated, first with melanoma epitopes included into Influenza virosomes (group 1), and second with a heterologous prime-boost protocol priming with a recombinant Vaccinia virus, and boosting with Influenza virosomes (group 2). Five melanoma epitopes from three different melanoma differentiation antigens were included into Influenza virosomes, that cross-stimulate CD4+ T cells and are endowed with high adjuvant capacity in the generation of CTL. The same five melanoma epitopes, two co-stimulatory molecules CD80 and CD86, and the CD40 ligand, a marker known to play a crucial role in CTL generation and memory maintenance were encoded in a recombinant Vaccinia virus. GM-CSF will be administered as a supporting cytokine. Both Influenza virosomes and octo-recombinant Vaccinia virus are innovative and original constructs assessed for the first time in human. Immunotherapy foresees 12 weekly immunizations for each group. Toxicity and adverse events will be monitored clinically. Immunological efficacy will be assessed dynamically by ex-vivo multimer analysis, Elispot, and quantitative real-time PCR for up to 3 months following completion of immunotherapy schedule. Disease free survival will be assessed by 4-monthly serial clinic visits, including physical and FDG-PET examinations, for a follow-up time of 2 years. Quality of life will be assessed with a dedicated FACT-BRM 4 questionnaire.
Contemporary Clinical Trials 04/2008; 29(2):165-81. · 1.81 Impact Factor
