The optimal diagnostic cut-off of WBC and PMN counts for joint aspiration in periprosthetic joint infection is 2479/µL and 67%, respectively: ICM criteria thresholds are too high.

BACKGROUND: Various organizations have published definitions for periprosthetic joint infection (PJI) with significant differences in the cut-offs of white blood cell (WBC) count and polymorphonuclear (PMN) leukocyte cells. Herein, we aim to analyze optimal cut-offs in patients which are planned to undergo a prosthesis revision and compare them with the actual published thresholds of the International Consensus Meeting (ICM) and European Bone and Joint Infection Society (EBJIS). METHODS: A test kit was compiled in a monocentric prospective study, according to the ICM criteria (2018) and 2021 EBJIS criteria. The kit was implemented using: blood samples (including leukocyte count and C-reactive protein); samples for examining the synovial fluid (WBC count, PMN cell differentiation, microbiological culture for incubation over 14 days, alpha-defensin ELISA laboratory test, and leukocyte-esterase test). The cut-offs for WBC and PMN counts were investigated using ROC analyses and Youden index. The ICM 2018 criteria were applied, using alpha-defensin in all cases. Patients which have to undergo a prosthesis revision were included, a pre-operative joint aspiration had been performed, and the patients had been followed up prospectively. RESULTS: 405 patients were examined with the compiled test kit; 100% had a complete dataset with respect to alpha-defensin; 383 patients, according to WBC count; and 256, according to PMN cell differentiation The cut-off of 2478.89 cells/µl in the WBC count (sensitivity: 87.70%; specificity: 88.10%) and the cut-off of 66.99% in PMN differentiation showed the best accuracy (sensitivity: 86.00%; specificity: 88.80%). Other published cut-offs for WBC were tested in this cohort and showed the following accuracy: 3000/µl (EBJIS/ICM; sensitivity: 82.10%; specificity: 91.00%), 2000/µl (sensitivity: 89.60%; specificity: 83.40%), and 1500/µl (sensitivity: 91.50%; specificity: 75.00%). The published cut-offs for PMN had the following accuracy in this cohort: 80% (ICM; sensitivity: 66.3%; specificity: 96.50%), 70% (sensitivity: 82.6%; specificity: 90%), and 65% (EBJIS, sensitivity: 86%; specificity: 88.8%). CONCLUSIONS: This study aims to improve current cut-offs for PMN- and WB-Count, even though PJI diagnosis is based on the combination of all defined tests. The optimal diagnostic cut-off of WBC and PMN counts was found to be 2479/µL and 67%, respectively, whereas ICM cut-offs in this cohort seem too high, as they provide high specificity but very low sensitivity. On the other hand, a cut-off for WBC count of 1500/µl alone would be very low, leading to low specificity and very high suspicion of PJI. The current consensus guidelines could be actualized considering these results to significantly improve the diagnostic quality. LEVEL OF EVIDENCE: II.

[Implementation of a standardized clinical test kit for diagnostics of periprosthetic infections in the clinical routine. German version]. / Implementierung eines standardisierten Test-Kits zur Diagnostik von periprothetischen Infektionen in der klinischen Routine.

BACKGROUND: The number of primary arthroplasties is increasing and the proportion of revision arthroplasties is becoming increasingly more important. The need for standardized and guideline-based diagnostics for the safe detection of a periprosthetic joint infection (PJI) is becoming apparent. In the past 10 years various organizations have published definitions and diagnostic guidelines. The implementation of an inhouse standard test kit could help to simplify the process and could improve the diagnostic quality. METHOD: In 2016 a test kit was compiled in a monocentric prospective study, taking the International Consensus Meeting (ICM) criteria 2014 and the Infectious Diseases Society of America (IDSA) criteria into account, which also fulfils the definitions of the ICM criteria 2018 and criteria of the European Bone and Joint Infection Society 2021. The test kit was implemented in the clinical setting of a special department for aseptic and septic revision arthroplasty. The usability and accuracy of the test kit were examined. RESULTS: The test kit was implemented using blood samples (leukocyte count; C­reactive protein, CRP), samples for examining the synovial fluid (white blood cell count, PMN cell differentiation, microbiological culture for incubation over 14 days, alpha-defensin enzyme-linked immunosorbent assay, ELISA, leukocyte esterase test strips) together with information and request forms. Between April 2016 and February 2020 a total of 405 patients were investigated. Within 3 calendar years, the use of the test kit increased from 59% initially to 86%, and finally to 96% of cases in the third calendar year. The leukocyte esterase test strip was reliable in only 72%, due to undifferentiated readability or blood contamination. The costs increased by the only commercially available alpha-defensin ELISA test by approx. 52€ per puncture. The best individual test showed a sensitivity/specificity of 92.8%/95.2% with alpha-defensin. It was calculated which combinations showed a similar test quality and different combinations, such as CRP+ cell count+ microbiology showed a sensitivity/specificity both of around 90%. Metallosis is a challenge for preoperative PJI diagnostics. DISCUSSION: In a prospective study it was shown, that the implementation of the standardized test kit lead to a guideline based PJI diagnostic in all cases and thus to a significantly increase of the diagnostic quality. There is currently no single test that reliably excludes or proves an infection. The alpha-defensin laboratory ELISA test showed the best test accuracy, whereby the consideration of test combinations is obligatory and at the same time safe.

Implementation of a standardized clinical test kit for diagnostics of periprosthetic infections in the clinical routine.

BACKGROUND: The number of primary arthroplasties is increasing and the proportion of revision arthroplasties is becoming increasingly more important. The need for standardized and guideline-based diagnostics for the safe detection of a periprosthetic joint infection (PJI) is becoming apparent. In the past 10 years various organizations have published definitions and diagnostic guidelines. The implementation of an inhouse standard test kit could help to simplify the process and could improve the diagnostic quality. METHOD: In 2016 a test kit was compiled in a monocentric prospective study, taking the International Consensus Meeting (ICM) criteria 2014 and the Infectious Diseases Society of America (IDSA) criteria into account, which also fulfils the definitions of the ICM criteria 2018 and criteria of the European Bone and Joint Infection Society 2021. The test kit was implemented in the clinical setting of a special department for aseptic and septic revision arthroplasty. The usability and accuracy of the test kit were examined. RESULTS: The test kit was implemented using blood samples (leukocyte count; C­reactive protein, CRP), samples for examining the synovial fluid (white blood cell count, PMN cell differentiation, microbiological culture for incubation over 14 days, alpha-defensin enzyme-linked immunosorbent assay, ELISA, leukocyte esterase test strips) together with information and request forms. Between April 2016 and February 2020 a total of 405 patients were investigated. Within 3 calendar years, the use of the test kit increased from 59% initially to 86%, and finally to 96% of cases in the third calendar year. The leukocyte esterase test strip was reliable in only 72%, due to undifferentiated readability or blood contamination. The costs increased by the only commercially available alpha-defensin ELISA test by approx. 52€ per puncture. The best individual test showed a sensitivity/specificity of 92.8%/95.2% with alpha-defensin. It was calculated which combinations showed a similar test quality and different combinations, such as CRP+ cell count+ microbiology showed a sensitivity/specificity both of around 90%. Metallosis is a challenge for preoperative PJI diagnostics. DISCUSSION: In a prospective study it was shown, that the implementation of the standardized test kit lead to a guideline based PJI diagnostic in all cases and thus to a significantly increase of the diagnostic quality. There is currently no single test that reliably excludes or proves an infection. The alpha-defensin laboratory ELISA test showed the best test accuracy, whereby the consideration of test combinations is obligatory and at the same time safe.

Modular knee arthrodesis secures limb, mobility, improves quality of life, and leads to high infection control in periprosthetic knee infection, when revision knee arthroplasty is not an option.

INTRODUCTION: This study compared the outcome of knee arthrodesis versus hinged total knee arthroplasty (TKA) in patients suffering from periprosthetic joint infection (PJI). METHODS: 104 patients with PJI were treated using a two-stage exchange of failed TKA. In case of non reconstructable bone loss or loss of extension mechanism, a modular intramedullary arthrodesis nail was used for reimplantation [Knee Arthrodesis Module (KAM); n = 52]. The control group was retrospectively matched treated using a hinged revision TKA [Rotating Hinge Knee (RHK); n = 52]. PJI remission rates, functional outcome (WOMAC; KSS) and quality of life (SF-12), as well as comorbidities and pain were evaluated. RESULTS: Mean age was 72.5 years. Charlson Comorbidity Index was higher in the KAM group (3.3 vs. 2.8). PJI remission rate was 89.4% (88.5% vs. 90.4%, respectively). In case of reinfection, implant retention was mostly possible in the RHK group (7.7%), whereas amputations were mostly performed in the KAM group (9.6%). Significant pain reduction (VAS 7.9-2.8) was achieved in both groups. Walking distance was significantly reduced in the KAM groups versus the RHK group (504 vs. 1064 m). WOMAC and KSS function scores were significantly reduced in the KAM group (25 vs. 40 and 35 vs. 64). Only moderate reduction in quality of life in the KAM group was observed (SF-12 physical: 34 vs. 40; SF-12 mental: 51 vs. 56) respectively. CONCLUSIONS: Arthrodesis using a modular intramedullary nail is an alternative for limb salvage, pain reduction, and preservation of quality of life and everyday mobility, when revision TKA is not an option. This study presents the largest number of case, comparing the outcome after performing an arthrodesis versus hinged TKA after septic failed TKA.

Expandable spacers provide better functional outcomes than static spacers in minimally invasive transforaminal lumbar interbody fusion.

BACKGROUND: Transforaminal lumbar interbody fusion is an effective and frequently performed surgical treatment of chronic lower back pain. Expandable interbody spacers are designed to create greater disc height through in situ expansion. It remains unclear whether the benefits of expandable technology will translate into clinical benefits. The current study compares expandable to static interbody spacers. METHODS: This is a retrospective study of 99 patients (48 static and 51 expandable) at a single site. Radiographs were collected preoperatively and at 3 months postoperatively. Standard of care at this site requires radiographs to be taken past 3 months only if patients are suffering from a severe recurrence of symptoms. Patient reported outcomes, Oswestry disability index (ODI) and visual analog scale (VAS), were collected preoperatively, at 1 and 3 months postoperatively. Patients were contacted by the surgeon and patient reported outcomes were collected at a final time point. Average final follow-up for was 67.1±16.3 months and for expandable patients it was 43.0±4.2 months. RESULTS: At 3 months postoperatively and at final follow-up, patients treated with expandable interbody spacers had significantly lower average ODI scores than patients with static interbody spacers. Both groups reported significant reductions in VAS scores through all follow-up. At 4 years postoperative 8 static group patients and 3 expandable group patients returned for recurrence of symptoms. CONCLUSIONS: Expandable interbody spacers in this study were found to be comparable to static interbody spacers, with improvements in VAS and ODI scores.

[The S2k guideline: Indications for knee endoprosthesis : Evidence and consent-based indications for total knee arthroplasty]. / S2k-Leitlinie: Indikation Knieendoprothese : Evidenz- und konsensbasierte Indikationsstellung in der Knie-Endoprothetik (EKIT-Knie).

Total knee arthroplasty (TKA) is one of the most frequent surgical procedures in orthopaedic surgery. Until now there have not been any standardized indication criteria, which might contribute to the large geographical differences in the frequency of TKA. This guideline aims to consent minimal requirements (main criteria), additional important aspects (minor criteria), as well as relative and absolute contraindications for TKA. The following main criteria have been consented: knee pain, radiological confirmation of osteoarthritis or osteonecrosis, inadequate response to conservative treatment, adverse impact of knee disease on the patient's quality of life and the burden of suffering due to the knee disease. Relative contraindications have been consented as severe general disease with reduced life expectancy and a BMI ≥40; absolute contraindications are an active infection and if the patient is not able to undergo major surgery.

Advantages of a multi-state approach in surgical research: how intermediate events and risk factor profile affect the prognosis of a patient with locally advanced rectal cancer.

BACKGROUND: Standard survival analysis fails to give insight into what happens to a patient after a first outcome event (like first relapse of a disease). Multi-state models are a useful tool for analyzing survival data when different treatments and results (intermediate events) can occur. Aim of this study was to implement a multi-state model on data of patients with rectal cancer to illustrate the advantages of multi-state analysis in comparison to standard survival analysis. METHODS: We re-analyzed data from the RCT FOGT-2 study by using a multi-state model. Based on the results we defined a high and low risk reference patient. Using dynamic prediction, we estimated how the survival probability changes as more information about the clinical history of the patient becomes available. RESULTS: A patient with stage UICC IIIc (vs UICC II) has a higher risk to develop distant metastasis (DM) or both DM and local recurrence (LR) if he/she discontinues chemotherapy within 6 months or between 6 and 12 months, as well as after the completion of 12 months CTx with HR 3.55 (p = 0.026), 5.33 (p = 0.001) and 3.37 (p < 0.001), respectively. He/she also has a higher risk to die after the development of DM (HR 1.72, p = 0.023). Anterior resection vs. abdominoperineal amputation means 63% risk reduction to develop DM or both DM and LR (HR 0.37, p = 0.003) after discontinuation of chemotherapy between 6 and 12 months. After development of LR, a woman has a 4.62 times higher risk to die (p = 0.006). A high risk reference patient has an estimated 43% 5-year survival probability at start of CTx, whereas for a low risk patient this is 79%. After the development of DM 1 year later, the high risk patient has an estimated 5-year survival probability of 11% and the low risk patient one of 21%. CONCLUSIONS: Multi-state models help to gain additional insight into the complex events after start of treatment. Dynamic prediction shows how survival probabilities change by progression of the clinical history.

Prospective randomized controlled comparison of posterior vs. posterior-anterior stabilization of thoracolumbar incomplete cranial burst fractures in neurological intact patients: the RASPUTHINE pilot study.

PURPOSE: If surgery for thoracolumbar incomplete cranial burst fractures (Magerl A3.1.1) is necessary, the ideal stabilization strategy still remains undetermined. To justify posterior-anterior stabilization, which generates higher costs and potentially higher morbidity vs. posterior-only stabilization, clinical trials with sufficient power and adequate methodology are required. This prospective randomized single-centre pilot trial was designed to enable sufficient sample-size calculation for a randomized multicentre clinical trial (RASPUTHINE). METHODS: Patients with a traumatic thoracolumbar (Th11-L2) incomplete burst fracture (Magerl A3.1.1) were randomly assigned either to the interventional group (posterior-anterior) or to the control group (posterior-only). Primary endpoint of the study was the clinical outcome measured using the Oswestry Disability Index (ODI) at 24 months. Radiological outcome was assessed as secondary endpoint by evaluation of mono- and bisegmental kyphotic angulation and monosegmental fusion. RESULTS: 21 patients were randomly assigned to interventional group (n = 9) or control group (n = 12). One posterior-only treated patient showed a severe initial loss of correction resulting in a crossover to additional anterior bisegmental fusion. The ODI measures at the primary study endpoint showed less but insignificant (p = 0.67) disability for the interventional group over the control group (13.3 vs. 19.3%). Comparison of preoperative bisegmental kyphosis in supine position with the bisegmental kyphosis at 24-month FU in upright position showed a worsened kyphosis for the control group (10.7° â†’ 15.6°), whereas an improved kyphosis (11° â†’ 8.3°) was detectable for the interventional group. CONCLUSION: The results of this pilot RCT showed less disability for the posterior-anterior group linked with a significant better restoration of the sagittal profile in comparison with the posterior-only group. To detect a clinically significant difference using the ODI and assuming a 20% loss of FU rate, a total of 266 patients have to be studied in the multicentre trial.

Observation of coherent elastic neutrino-nucleus scattering.

The coherent elastic scattering of neutrinos off nuclei has eluded detection for four decades, even though its predicted cross section is by far the largest of all low-energy neutrino couplings. This mode of interaction offers new opportunities to study neutrino properties and leads to a miniaturization of detector size, with potential technological applications. We observed this process at a 6.7σ confidence level, using a low-background, 14.6-kilogram CsI[Na] scintillator exposed to the neutrino emissions from the Spallation Neutron Source at Oak Ridge National Laboratory. Characteristic signatures in energy and time, predicted by the standard model for this process, were observed in high signal-to-background conditions. Improved constraints on nonstandard neutrino interactions with quarks are derived from this initial data set.

Topologically protected bound states in photonic parity-time-symmetric crystals.

Parity-time (PT)-symmetric crystals are a class of non-Hermitian systems that allow, for example, the existence of modes with real propagation constants, for self-orthogonality of propagating modes, and for uni-directional invisibility at defects. Photonic PT-symmetric systems that also support topological states could be useful for shaping and routing light waves. However, it is currently debated whether topological interface states can exist at all in PT-symmetric systems. Here, we show theoretically and demonstrate experimentally the existence of such states: states that are localized at the interface between two topologically distinct PT-symmetric photonic lattices. We find analytical closed form solutions of topological PT-symmetric interface states, and observe them through fluorescence microscopy in a passive PT-symmetric dimerized photonic lattice. Our results are relevant towards approaches to localize light on the interface between non-Hermitian crystals.

[CMV-associated gastric ulcer in an immunocompetent male patient]. / CMV-assoziiertes Ulcus ventriculi bei einem immunkompetenten Patienten.

This article reports the case of a 45-year-old male immunocompetent patient who presented with acute epigastric pain and vomiting. Diagnostic tests confirmed a recent cytomegalovirus (CMV) infection as a contributory cause of a florid gastric ulcer. Primary CMV infections affecting the upper gastrointestinal tract are rare in immunocompetent adults. In this case treatment with a proton pump inhibitor and eradication of concomitant Helicobacter pylori colonization led to a full recovery. Anti-CMV treatment was not necessary.

[In process]. / Insomnie, anxiété: faut-il réguler la prescription des benzodiazépines?

Benzodiazepine hypnotics bear a higher risk of high dose dependence than benzodiazepine anxiolytics, according to a recent study in Luxemburg. This article summarizes the main indications of these molecules and the current treatment recommendations. It provides an overview of public health actions of the past and the future to reduce their excessive consumption.

[Preclinical and clinical treatment of instable pelvic injuries : Results of an online survey]. / Präklinische und klinische Versorgung der instabilen Beckenverletzung : Ergebnisse einer Online-Umfrage.

Instable pelvic injuries are often associated with a high blood loss, which can effectively be curtailed by rapid external stabilization of the pelvis. The S3 guidelines on the treatment of multiple trauma and the severely injured recommend an initial stability testing in cases of an instable pelvis and hemodynamic instability even though the sensitivity is very low, with subsequent external stabilization. Radiological diagnostic procedures are also becoming more important for early diagnostics. An online survey of the current management of instable pelvic injuries was carried out with 266 participants via the e-mail distribution list of the German Society of Trauma Surgery (DGU).Most answers in the survey were received from very experienced senior and chief physicians at level 1 trauma centers. The vast majority of the participants recommended carrying out mechanical stabilization testing and most wanted to do the testing themselves independent of any previous findings. Most participants would only carry out a pelvic stabilization if they themselves had recognized instability during the stability testing and many of them even in cases of hemodynamic instability alone, although several studies have reported a very low sensitivity of 26-44 % for stability testing. The preferred procedure for emergency stabilization in the emergency room was the pelvic sling, which in contrast to invasive tools was often implemented before radiological imaging was completed. In preclinical treatment the vacuum mattress was used more often for stabilization than the pelvic sling. In radiological examinations a whole body computed tomography (CT) scan was mostly used, sometimes combined with an anteroposterior pelvic x-ray. In cases of persisting hemorrhage in spite of external stabilization, most participants preferred a pelvic tamponade but angioembolization was also highly rated.Because many of the participants relied on their own findings from stability testing for a decision on external emergency stabilization despite the very low sensitivity, in cases of false negative testing there is a risk of insufficient treatment resulting in life-threatening hemorrhage. From our viewpoint, it therefore makes sense to treat patients with a suspicion of instable pelvic fractures based on the trauma mechanism and clinical examination (without mechanical stability testing) with non-invasive external pelvic stabilization as early as possible.

ICSH guidelines for the standardization of bone marrow immunohistochemistry.

Bone marrow (BM) tissue biopsy evaluation, including trephine biopsy and clot section, is an integral part of BM investigation and is often followed by ancillary studies, in particular immunohistochemistry (IHC). IHC provides in situ coupling of morphological assessment and immunophenotype. The number of different IHC tests that can be applied to BM trephine biopsies and the number of indications for IHC testing is increasing concurrently with the development of flow cytometry and molecular diagnostic methods. An international Working Party for the Standardization of Bone Marrow IHC was formed by the International Council for Standardization in Hematology (ICSH) to prepare a set of guidelines for the standardization of BM IHC based on currently available published evidence and modern understanding of quality assurance principles as applied to IHC in general. The guidelines were discussed at the ICSH General Assemblies and reviewed by an international panel of experts to achieve further consensus and represent further development of the previously published ICSH guidelines for the standardization of BM specimens handling and reports.

[Epidural injection shows no advantages over oral medication and physiotherapy in the treatment of sciatica, irrespective of the duration of symptoms]. / Kein Vorteil der epiduralen Injektion vs. oraler Medikation und Physiotherapie bei Ischialgie, unabhängig von der Beschwerdedauer.

BACKGROUND: The study presented here investigated the short-term effectiveness of one-off lumbar caudal epidural injection (EI) in sciatica in relationship to the reported duration of pain. MATERIALS AND METHODS: This retrospective analysis involved 106 consecutive in-patients who received either conservative treatment (Group I) or an additional EI on the first day of their treatment (Group II). Both groups were divided according to the duration of symptoms at the time of admission (less than three months, or more than six months). Propensity score matching was performed for the whole collective and the resulting subgroups. This incorporated gender, age and pain intensity at the time of admission. The target parameter were changes on a visual analogue scale (VAS) of pain intensity on days D1, D3, and D10 depending on the respective treatment. A routine evaluation of the mental variables anxiety, depression and somatisation was performed as part of the examination upon admission and their relationship to the success of treatment was later assessed. RESULTS: The mean age of the patients was 61.7 (± 11.6) in Group I and 63.6 (± 13.6) in Group II. 59 % of the patients were female (n = 63). The Lasègue sign was prevalent in 45 % of Group I and 51 % of Group II. The intensity of pain on the day of admission was similar in both groups (7.0 ± 1.0 for Group I, 6.7 ± 1.8 for Group II). The length of stay on the ward was also similar in both groups (10.2 ± 3.9 and 9.4 ± 3.7 d, respectively). It was found that, independent of the duration of symptoms, injection treatment was significantly more effective than conservative treatment only in the early stages (D1 and D3, p < 0.001). No differences could be found in the expression of these mental variables between treatment groups, as these factors showed no influence on the results of therapy. CONCLUSIONS: In the context of acute treatment a once only lumbar caudal epidural injection represents at most a short-term effectiveness for the therapy of sciatica. The results presented here indicate that neither the duration of symptoms nor the measured psychometric variables show any effect on the success of therapy.

Attosecond correlated dynamics of two electrons passing through a transition state.

The strong-field induced decay of a doubly excited, transient Coulomb complex Ar**→Ar(2+)+2e(-) is explored by tracing correlated two-electron emission in nonsequential double ionization of Ar as a function of the carrier-envelope phase. Using <6 fs pulses, electron emission is essentially confined to one optical cycle. Classical model calculations support that the intermediate Coulomb complex has lost memory of its formation dynamics and allows for a consistent, though model-dependent definition of "emission time," empowering us to trace transition-state two-electron decay dynamics with sub-fs resolution. We find a most likely emission time difference of ∼200±100 as.

Impact of the new european paediatric regulatory framework on ethics committees: overview and perspectives.

AIM: To evaluate the impact of the new European paediatric regulatory framework on the activities of Ethics Committees operating in Europe and to assess their involvement and interest in paediatric research. METHODS: Task-force in Europe for Drug Development for the Young Network of Excellence and Relating Expectations and Needs to the Participation and Empowerment of Children in Clinical Trials project set up an inventory of Ethics Committees existing in Europe and conducted a survey on their approach to paediatric trials. RESULTS: Ethics Committees operating in 22 European Countries participated in this survey. Results showed a high lack of knowledge, understanding and awareness of the current European paediatric regulatory framework and a lack of involvement of Ethics Committees in paediatric research, especially in terms of training and education, demonstrated also by the decreasing number of Ethics Committees answering exhaustively to the whole questionnaire. The majority of participating Ethics Committees expressed interest in future initiatives related to paediatric research. CONCLUSIONS: Despite a limited knowledge and understanding of the current paediatric regulatory framework, a significant number of Ethics Committees operating in Europe show interest in initiatives related to paediatric research. Networking may be an essential tool to be used to enhance Ethics Committees role in supporting paediatric research. Any initiative should be undertaken at European level in collaboration with European Union Institutions.

Expression of Y-box-binding protein YB-1 allows stratification into long- and short-term survivors of head and neck cancer patients.

BACKGROUND: Histology-based classifications and clinical parameters of head and neck squamous cell carcinoma (HNSCC) are limited in their clinical capacity to provide information on prognosis and treatment choice of HNSCC. The primary aim of this study was to analyse Y-box-binding protein-1 (YB-1) protein expression in different grading groups of HNSCC patients, and to correlate these findings with the disease-specific survival (DSS). METHODS: We investigated the expression and cellular localisation of the oncogenic transcription/translation factor YB-1 by immunohistochemistry on tissue micro arrays in a total of 365 HNSCC specimens and correlated expression data with clinico-pathological parameters including DSS. RESULTS: Compared with control tissue from healthy individuals, a significantly (P<0.01) increased YB-1 protein expression was observed in high-grade HNSCC patients. By univariate survival data analysis, HNSCC patients with elevated YB-1 protein expression had a significantly (P<0.01) decreased DSS. By multivariate Cox regression analysis, high YB-1 expression and nuclear localisation retained its significance as a statistically independent (P<0.002) prognostic marker for DSS. Within grade 2 group of HNSCC patients, a subgroup defined by high nuclear and cytoplasmic YB-1 levels (co-expression pattern) in the cells of the tumour invasion front had a significantly poorer 5-year DSS rate of only 38% compared with overall 55% for grade 2 patients. Vice versa, the DSS rate was markedly increased to 74% for grade 2 cancer patients with low YB-1 protein expression at the same localisation. CONCLUSION: Our findings point to the fact that YB-1 expression in combination with histological classification in a double stratification strategy is superior to classical grading in the prediction of tumour progression in HNSCC.

Dopant-induced ignition of helium nanodroplets in intense few-cycle laser pulses.

We demonstrate ultrafast resonant energy absorption of rare-gas doped He nanodroplets from intense few-cycle (~10 fs) laser pulses. We find that less than 10 dopant atoms "ignite" the droplet to generate a nonspherical electronic nanoplasma resulting ultimately in complete ionization and disintegration of all atoms, although the pristine He droplet is transparent for the laser intensities applied. Our calculations at those intensities reveal that the minimal pulse length required for ignition is about 9 fs.