Repeat two-stage exchange arthroplasty for recurrent periprosthetic hip or knee infection: what are the chances for success?

INTRODUCTION: Two-stage revision is a frequently chosen approach to treat chronic periprosthetic joint infection (PJI). However, management of recurrent infection after a two-stage exchange remains debated and the outcome of a repeat two-stage procedure is unclear. This study investigates the success rates of repeat two-stage exchange arthroplasty and analyzes possible risk factors for failure. MATERIALS AND METHODS: We retrospectively identified 55 patients (23 hips, 32 knees) who were treated with repeat resection arthroplasty and planned delayed reimplantation for recurrent periprosthetic joint infection between 2010 and 2019 after a prior two-stage revision at the same institution. The minimum follow-up was 12 months with a median follow-up time of 34 months (IQR 22-51). The infection-free survival, associated revision surgeries, and potential risk factors for further revision were analyzed using Kaplan-Meier survival curves and comparative non-parametric testing. RESULTS: 78% (43/55) underwent reimplantation after a repeat implant removal. Of those who completed the second-stage surgery, 37% (16/43) underwent additional revision for infection and 14% (6/55) underwent amputation. The reinfection-free implant survivorship amounted to 77% (95% CI 64-89%) after 1 year and 38% (95% CI 18-57%) after 5 years. Patients with a higher comorbidity score were less likely to undergo second-stage reimplantation (median 5 vs. 3, p = 0.034). Furthermore, obese patients (p = 0.026, Fisher's exact test) and diabetics (p < 0.001, log-rank test) had a higher risk for further infection. Most commonly cultures yielded polymicrobial growth at the repeat two-stage exchange (27%, 15/55) and at re-reinfection (32%, 9/28). Pathogen persistence was observed in 21% (6/28) of re-reinfected patients. CONCLUSION: The success rates after repeat two-stage exchange arthroplasty are low. Patients must be counseled accordingly and different modes of treatment should be considered.

Good to excellent long-term survival of a single-design condylar constrained knee arthroplasty for primary and revision surgery.

PURPOSE: The purpose of the study was to determine the long-term survivorship, functional outcomes of a single-design condylar constrained (CCK) TKA in primary and revision cases as well as to assess specific risk factors for failure. It was hypothesized that primary CCK TKA had a better survival than revision knees. METHODS: One hundred and forty three patients who underwent revision TKA (n = 119) or complex primary TKA (n = 24) using a single-design condylar constrained knee system (Genesis CCK, Smith & Nephew) performed at a single institution between 1999 and 2008 were retrospectively included. The median follow-up amounted to 11.8 years (IQR 10.3-14.4). Implant survivorship was analyzed using Kaplan-Meier survival estimates and multivariate Cox regression analysis to identify risk factors for failure. Function was determined using the Oxford Knee Score (OKS). RESULTS: The implant survival was 86.4% after five, 85.5% after ten and 79.8% at 15 years. A reduced implant survivorship was found in males (HR 5.16, p = 0.001), smokers (HR 6.53, p = 0.004) and in obese patients (HR 2.26, p = 0.095). Patients who underwent primary TKA had a higher revision-free implant survivorship compared to revision TKA at 15 years (100% vs. 76%, p = 0.036). The main cause for re-revision was infection in 10% of all revision TKA performed with the CCK design included, while no case was revised for instability. The median OKS was 39 (IQR 35-44) in 102 patients available for long-term functional outcome. CONCLUSION: CCK implants are associated with excellent long-term survival when used in primary TKA; however, survival was worse when used during revision TKA. Males, smokers, obese patients and are at higher risk for revision. While instability and aseptic loosening were rare, infection remains a major concern. LEVEL OF EVIDENCE: Level IV, retrospective observational study.

Acceptable mid- to long-term survival rates and functional outcomes following a single design rotating hinge total knee arthroplasty.

PURPOSE: This study first analyzes implant survival of this single design modular rotating hinge knee and identifies potential risk factors for failure and evaluates joint function using the postoperative WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score, active flexion and extension deficit. METHODS: 131 prostheses implanted for failure of prior total knee arthroplasty (n = 120) or complex primary procedures (n = 11) using a single modular implant (MUTARS-modular universal tumor and revision system GenuX, Implantcast, Buxtehude, Germany) between 2006 and 2014 including 73 patients treated for periprosthetic joint infection with a two-stage revision protocol were retrospectively identified. Implant survival was assessed using the Kaplan-Meier method; potential risk factors were identified using the log-rank test, as well as non-parametric analysis. Postoperative function was assessed using the WOMAC and measurement of range of motion. RESULTS: After a median follow-up of 62 months, 37 implants required implant revision (28%). Five-year survival was 69.7% [95% CI (confidence interval) 60.9-78.5] with periprosthetic (re-) infection being the main cause for failure (15%), followed by aseptic loosening (9%). In cases of periprosthetic infection, infection-free survival was 83% at 5 years (95% CI 74-92) with twelve patients suffering reinfection (16%).While body mass index (p = 0.75), age (p = 0.16) or indication for rotating hinge knee arthroplasty (p = 0.25) had no influence on survival, Charlson comorbidity score (CCI) (p = 0.07) and number of previous revision surgeries (p = 0.05) correlated with implant failure. There was trend (p = 0.1) for improved survival in fully cemented implants. Mean postoperative WOMAC was 127(range 55-191), 11 patients (15%) had limited knee extension. CONCLUSIONS: Rotating hinge total knee arthroplasty using a single modular implant shows acceptable survival rates and function compared to previous studies with (re-)infection being the most relevant mode of failure. Patients with a high CCI and multiple previous surgeries are at increased risk for failure. LEVEL OF EVIDENCE: Retrospective cohort study, III.

Do Positive Cultures at Second Stage Re-Implantation Increase the Risk for Reinfection in Two-Stage Exchange for Periprosthetic Joint Infection?

BACKGROUND: Intraoperative cultures are important in the diagnosis and targeted treatment of periprosthetic joint infection (PJI). Positive cultures at reimplantation during a two-stage exchange are discussed as a risk factor for reinfection. The aim of this study is the investigation of the incidence and risk factors for positive cultures during reimplantation. METHODS: We retrospectively identified 204 patients (111 knees, 93 hips) who were treated between 2012 and 2016 for PJI using a two-stage exchange protocol at a median follow-up of 42 months. PJI was diagnosed using the criteria of the musculoskeletal infection society (MSIS) of 2011. All cultural findings from first and second stage surgery were recorded. The primary endpoint was revision for infection. Risk factors for positive cultures and reinfection were analyzed. RESULTS: During reimplantation 25% (51/204) of patients had at least one positive culture, in 19.1% (39/204) only a single culture. Patients with culture-negative infections had a higher risk for positive cultures at reimplantation (HR 2.946 (95% CI 1.247-6.961), P = .014) and patients with infected total hip arthroplasty (THA) (HR 3.547 (95% CI 1.7-7.4), P = .001). Patients with positive cultures during reimplantation had a higher risk for reinfection (HR 2.27 (95% CI 1.181-4.363), P = .014) as well as patients with a single positive culture (HR 2.421 (95% CI 1.139-5.143), P = .021). CONCLUSION: As positive cultures are common and increase reinfection risk irrespective of their numbers, longer antibiotic therapy following reimplantation can be an option. Single positive cultures in reimplantation surgery should not be considered contamination.

The potential of anti-infectives and immunomodulators as therapies for asthma and asthma exacerbations.

Asthma is responsible for approximately 25,000 deaths annually in Europe despite available medicines that maintain asthma control and reduce asthma exacerbations. Better treatments are urgently needed for the control of chronic asthma and reduction in asthma exacerbations, the major cause of asthma mortality. Much research spanning >20 years shows a strong association between microorganisms including pathogens in asthma onset, severity and exacerbation, yet with the exception of antibiotics, few treatments are available that specifically target the offending pathogens. Recent insights into the microbiome suggest that modulating commensal organisms within the gut or lung may also be a possible way to treat/prevent asthma. The European Academy of Allergy & Clinical Immunology Task Force on Anti-infectives in Asthma was initiated to investigate the potential of anti-infectives and immunomodulators in asthma. This review provides a concise summary of the current literature and aimed to identify and address key questions that concern the use of anti-infectives and both microbe- and host-based immunomodulators and their feasibility for use in asthma.

Influenza burden, prevention, and treatment in asthma-A scoping review by the EAACI Influenza in asthma task force.

To address uncertainties in the prevention and management of influenza in people with asthma, we performed a scoping review of the published literature on influenza burden; current vaccine recommendations; vaccination coverage; immunogenicity, efficacy, effectiveness, and safety of influenza vaccines; and the benefits of antiviral drugs in people with asthma. We found significant variation in the reported rates of influenza detection in individuals with acute asthma exacerbations making it unclear to what degree influenza causes exacerbations of underlying asthma. The strongest evidence of an association was seen in studies of children. Countries in the European Union currently recommend influenza vaccination of adults with asthma; however, coverage varied between regions. Coverage was lower among children with asthma. Limited data suggest that good seroprotection and seroconversion can be achieved in both children and adults with asthma and that vaccination confers a degree of protection against influenza illness and asthma-related morbidity to children with asthma. There were insufficient data to determine efficacy in adults. Overall, influenza vaccines appeared to be safe for people with asthma. We identify knowledge gaps and make recommendations on future research needs in relation to influenza in patients with asthma.

Emerging roles of innate lymphoid cells in inflammatory diseases: Clinical implications.

Innate lymphoid cells (ILC) represent a group of lymphocytes that lack specific antigen receptors and are relatively rare as compared to adaptive lymphocytes. ILCs play important roles in allergic and nonallergic inflammatory diseases due to their location at barrier surfaces within the airways, gut, and skin, and they respond to cytokines produced by activated cells in their local environment. Innate lymphoid cells contribute to the immune response by the release of cytokines and other mediators, forming a link between innate and adaptive immunity. In recent years, these cells have been extensively characterized and their role in animal models of disease has been investigated. Data to translate the relevance of ILCs in human pathology, and the potential role of ILCs in diagnosis, as biomarkers and/or as future treatment targets are also emerging. This review, produced by a task force of the Immunology Section of the European Academy of Allergy and Clinical Immunology (EAACI), encompassing clinicians and researchers, highlights the role of ILCs in human allergic and nonallergic diseases in the airways, gastrointestinal tract, and skin, with a focus on new insights into clinical implications, therapeutic options, and future research opportunities.

Respiratory syncytial virus infection influences tight junction integrity.

Respiratory syncytial virus (RSV) is an important risk factor of asthma development and is responsible for severe respiratory tract infections. However, the influence of RSV infection on barrier function of bronchial epithelial cells in vitro and in vivo is still unclear. The aim of this study was to analyse the role of RSV in tight junction (TJ) regulation and to compare epithelial integrity between asthmatic and healthy individuals upon RSV infection. Healthy and asthmatic human bronchial epithelial cells (HBECs) were differentiated at air-liquid interface (ALI) and infected with RSV and ultraviolet (UV)-irradiated RSV. TJ expression and their integrity were analysed by quantitative polymerase chain reaction (qPCR), transepithelial resistance (TER) and paracellular flux. To determine the effect in vivo, BALB/c mice were infected intranasally with RSV or UV-irradiated RSV A2. Bronchoalveolar lavage and TJ integrity were analysed on days 1, 2, 4 and 6 post-infection by qPCR, bioplex and confocal microscopy. RSV increased barrier integrity in ALI cultures of HBEC from healthy subjects, but no effect was found in HBECs from asthmatics. This was not associated with an increase in TJ mRNA expression. In vivo, RSV induced lung inflammation in mice and down-regulated claudin-1 and occludin mRNA expression in whole lungs. Surprisingly, RSV infection was not observed in bronchial epithelial cells, but was found in the lung parenchyma. Decreased expression of occludin upon RSV infection was visible in mouse bronchial epithelial cells in confocal microscopy. However, there was no regulation of claudin-1 and claudin-7 at protein level.

Viral respiratory tract infections and asthma in early life: cause and effect?

Interactions between viral respiratory tract infections in infancy and childhood, and asthma development and exacerbation, are complex and intriguing. This review aims to unravel some of these complexities. Does severe respiratory viral infection early in life predispose to later asthma development, or is it indicative of a predisposition to allergic respiratory disease? How could variables such as age and severity of viral infection affect the interaction between respiratory viral infections and asthma? How could respiratory viral infection drive allergic sensitization? Here, we review the evidence surrounding these questions, and discuss current and future research and therapeutic approaches targeting the interplay between viral respiratory tract infection and asthma.

Evaluation of costs associated with fertility treatment leading to a live birth after one fresh transfer: A global perspective.

Considerable costs are associated with infertility treatment, but little evidence is available on the main drivers of treatment costs. This cost analysis investigated key costs for treatment with assisted reproductive technology (ART) and the proportion of costs attributed to the acquisition of recombinant human follicle-stimulating hormone (r-hFSH) alfa originator for one fresh embryo transfer (ET) leading to a live birth in Spain, Norway, the UK, Germany, Denmark, South Korea, Australia, and New Zealand. The total costs for one ART cycle with a fresh ET leading to a live birth varied between countries (€4108-€12,314). Costs for pregnancy and live birth were the major contributors in European countries, and the costs of oocyte retrieval, monitoring during ovarian stimulation, pregnancy, and live birth were the top contributors in the Asia-Pacific countries, included in this analysis. Acquisition costs for r-hFSH alfa originator contributed to only 5%-17% of the total costs of one ART cycle with one fresh ET leading to a live birth.

Effectiveness of recombinant human follicle-stimulating hormone (r-hFSH): recombinant human luteinizing hormone versus r-hFSH alone in assisted reproductive technology treatment cycles among women aged 35-40 years: A German database study.

This non-interventional study compared the effectiveness of recombinant human follicle-stimulating hormone (r-hFSH) and recombinant human luteinizing hormone (r-hLH) (2:1 ratio) versus r-hFSH alone for ovarian stimulation (OS) during assisted reproductive technology treatment in women aged 35-40 years, using real-world data from the Deutsches IVF-Register (D·I·R). Numerically higher clinical pregnancy (29.8% [95% CI 28.2, 31.6] vs. 27.8% [26.5, 29.2]) and live birth (20.3% [18.7, 21.8] vs. 18.0% [16.6, 19.4]) rates were observed with r-hFSH:r-hLH versus r-hFSH alone. The treatment effect was consistently higher for r-hFSH:r-hLH compared with r-hFSH alone in terms of clinical pregnancy (relative risk [RR] 1.16 [1.05, 1.26]) and live birth (RR 1.16 [1.02, 1.31]) in a post-hoc analysis of women with 5-14 oocytes retrieved (used as a surrogate for normal ovarian reserve), highlighting the potential benefits of r-hFSH:r-hLH for OS in women aged 35-40 years with normal ovarian reserve.

Comparative effectiveness of gonadotropins used for ovarian stimulation during assisted reproductive technologies (ART) in France: A real-world observational study from the French nationwide claims database (SNDS).

This comparative non-interventional study using data from the French National Health Database (Système National des Données de Santé) investigated real-world (cumulative) live birth outcomes following ovarian stimulation, leading to oocyte pickup with either originator recombinant human follicle-stimulating hormone (r-hFSH) products (alfa or beta), r-hFSH alfa biosimilars, or urinaries including mainly HP-hMG (menotropins), and marginally u-hFSH-HP (urofollitropin). Using data from 245,534 stimulations (153,600 women), biosimilars resulted in a 19% lower live birth (adjusted odds ratio (OR) 0.81, 95% confidence interval (CI) 0.76-0.86) and a 14% lower cumulative live birth (adjusted hazard ratio (HR) 0.86, 95% CI 0.82-0.89); and urinaries resulted in a 7% lower live birth (adjusted OR 0.93, 95% CI 0.90-0.96) and an 11% lower cumulative live birth (adjusted HR 0.89, 95% CI 0.87-0.91) versus originator r-hFSH alfa. Results were consistent across strata (age and ART strategy), sensitivity analysis using propensity score matching, and with r-hFSH alfa and beta as the reference group.

Negative regulation of airway responsiveness that is dependent on gammadelta T cells and independent of alphabeta T cells.

The mechanisms regulating airway function are complex and still poorly understood. In diseases such as asthma, involvement of immune-dependent mechanisms has been suggested in causing changes in airway responsiveness to bronchoconstrictors. We now demonstrate that gammadelta T cells can regulate airway function in an alphabeta T cell-independent manner, identifying them as important cells in pulmonary homeostasis. This function of gammadelta T cells differs from previously described immune-dependent mechanisms and may reflect their interaction with innate systems of host defense.

Patent foramen ovale is not associated with an increased risk of stroke recurrence.

BACKGROUND AND PURPOSE: Despite numerous studies suggesting a relationship between paradoxical embolism from a patent foramen ovale (PFO) and stroke, the role of PFO as a risk factor for cerebral ischaemia remains controversial. We therefore sought to determine the association between a RLS detected by contrast-enhanced transcranial Doppler ultrasonography (c-TCD) and recurrent stroke in an unselected population sample. METHODS: We analyzed the records of 763 patients with diagnosis of cerebral ischaemia at our institution. All patients had undergone TCD-based detection of RLS. Embolic signals have been measured both under resting conditions and after performing a Valsalva maneuver. For follow-up, all patients were contacted by mail, which included a standardized questionnaire. Endpoints of follow-up were defined as recurrence of cerebral ischaemia, occurrence of myocardial infarction or death from any cause. RESULTS: Follow-up data were available in 639 patients (83.7%). At baseline, a RLS was detected in 140 (28%) men and in 114 (42%) women. Ten shunt-carriers (1.6%) and 32 patients (5.0%) without RLS had suffered a recurrent stroke. After adjustment for age, sex, and atrial fibrillation, the hazard ratio of RLS for stroke recurrence was 0.86 (95% CI 0.41-1.79). The condition of RLS at rest adjusted for age, sex, stroke subtype, and cardiovascular risk factors was not found to increase the risk of stroke substantially (HR 1.16 [95% CI 0.41-3.29]) CONCLUSION: Our data suggest that the risk of recurrent stroke in subjects with PFO is not significantly increased in comparison with subject without it.

Healthy but not RSV-infected lung epithelial cells profoundly inhibit T cell activation.

BACKGROUND: Respiratory viruses, including respiratory syncytial virus (RSV), can cause asthma exacerbations and bronchiolitis. Both conditions are associated with enhanced cognate immune responses and inflammation and reduced immune regulation. Lung epithelial cells (LECs) can contribute to antiviral and allergic immune responses while gut epithelial cells can inhibit effector T cell responses. A study was performed to determine whether healthy LECs regulate antigen-specific T cell responses and if this regulation is lost during RSV infection. METHODS: LA4 cells, a murine LEC line, infected with RSV or primary murine LECs were co-cultured with ovalbumin-specific T cell receptor transgenic CD4+ T cells from DO11.10 mice and ovalbumin-pulsed bone marrow-derived dendritic cells (DC) to assess T cell proliferation by flow cytometry and cytokine production. RESULTS: The presence of LECs abrogated DC-induced T cell proliferation and significantly reduced T cell cytokine release. These effects of LECs were predominantly contact-dependent, primarily affected T cells directly and were partly mediated by transforming growth factor beta. Soluble factors and DC-mediated effects also contributed to T cell inhibition. RSV infection of LECs reduced their inhibitory capacity in an infection dose-dependent manner. This was independent of proinflammatory cytokines released by infected LECs, but in part due to Toll-like receptor activation and to infection-induced cell death. CONCLUSION: Healthy LECs are potent inhibitors of T cell activation, but this regulatory function is lost after RSV infection. These findings suggest a central role for LECs in maintaining the tolerogenic environment of healthy lungs. Loss of this regulatory capacity after viral infection may allow development of excessive cognate immune responses and pulmonary inflammation.

Lesion patterns in patients with cryptogenic stroke with and without right-to-left-shunt.

BACKGROUND AND PURPOSE: Despite numerous studies, the role of patent foramen ovale (PFO) as a risk factor for stroke due to paradoxical embolism is still controversial. On the assumption that specific lesion patterns, in particular multiple acute ischaemic lesions on diffusion-weighted magnetic resonance imaging, indicate a cardioembolic origin, we compared the MRI findings in stroke patients with right-to-left shunt (RLS) and those without. METHODS: The records of 486 patients with diagnosis of cerebral ischaemia were reviewed. For detection of RLS, contrast-enhanced transcranial Doppler (c-TCD) was carried out in all patients. An MRI scan of the brain was performed in all patients. Affected vascular territories were divided into anterior cerebral artery, middle cerebral artery, vertebrobasilar artery system including posterior cerebral artery, brain stem and cerebellar stroke, and strokes occurring in more than one territory. RESULTS: We did not find a specific difference in neuroradiological lesion patterns in patients with RLS compared with patients without RLS. In particular, 23 of 165 patients (13.9%) with RLS showed multiple ischaemic lesions on MRI in comparison with 45 of 321 patients (14.0%) without RLS (P = 0.98). These findings also applied for the subgroup of cryptogenic strokes with and without RLS. CONCLUSION: We found no association between an ischaemic lesion pattern that is considered as being typical for stroke due to cardiac embolism and the existence of PFO. Therefore, our findings do not provide any support for the common theory of paradoxical embolism as a major cause of stroke in PFO carriers.

Respiratory syncytial virus infection provokes airway remodelling in allergen-exposed mice in absence of prior allergen sensitization.

BACKGROUND: The mechanisms underlying exacerbation of asthma induced by respiratory syncytial virus (RSV) infection have been extensively studied in human and animal models. However, most of these studies focused on acute inflammation and little is known of its long-term consequences on remodelling of the airway tissue. OBJECTIVE: The aim of the study was to use a murine model of prolonged allergen-induced airway inflammation to investigate the effect of RSV infection on allergic airway inflammation and tissue remodelling. METHODS: We subjected mice to RSV infection before or during the chronic phase of airway challenges with OVA and compared parameters of airway inflammation and remodelling at the end-point of the prolonged allergen-induced airway inflammation protocol. RESULTS: RSV infection did not affect the severity of airway inflammation in any of the groups studied. However, RSV infection provoked airway remodelling in non-sensitized, allergen-challenged mice that did not otherwise develop any of the features of allergic airways disease. Increased collagen synthesis in the lung and thickening of the bronchial basal membrane was observed in non-sensitized allergen-challenged mice only after prior RSV infection. In addition, fibroblast growth factor (FGF)-2 but not TGF-beta(1) was increased in this group following RSV infection. CONCLUSION: Our data show for the first time that RSV infection can prime the lung of mice that are not previously systemically sensitized, to develop airway remodelling in response to allergen upon sole exposure via the airways. Moreover, our results implicate RSV-induced FGF-2 in the remodelling process in vivo.

Respiratory syncytial virus infection results in airway hyperresponsiveness and enhanced airway sensitization to allergen.

Viral respiratory infections can predispose to the development of asthma by mechanisms that are presently undetermined. Using a murine model of respiratory syncytial virus (RSV) infection, acute infection is associated with airway hyperresponsiveness as well as enhanced responses to subsequent sensitization to allergen. We demonstrate that acute viral infection results in increased airway responsiveness to inhaled methacholine and pulmonary neutrophilic and eosinophilic inflammation. This response is associated with predominant production of Th-1-type cytokines in peribronchial lymph node cells in vitro. Mice sensitized to ovalbumin via the airways after RSV infection developed increased airway responsiveness to methacholine and pulmonary eosinophilic and neutrophilic inflammation, associated with the predominant production of Th-2-type cytokines. Treatment of the mice with anti-IL-5 antibody abolished airway hyperresponsiveness and eosinophilic but not neutrophilic inflammation in both acutely infected mice and mice sensitized after infection. We conclude that RSV infection results in airway hyperresponsiveness in the acute phase and leads to changes in immune function that can enhance the effects of airway sensitization to antigen after infection. In both situations, airway hyperresponsiveness is closely associated with pulmonary eosinophilic inflammation. This model provides a means for further analyzing the influence of viral respiratory infections on airway sensitization and the development of altered airway responsiveness.

The late, but not early, asthmatic response is dependent on IL-5 and correlates with eosinophil infiltration.

Early-phase reactions (EPRs) and late-phase reactions (LPRs) are characteristic features of bronchial asthma, although the pathogenetic mechanisms responsible for each of the responses are not fully defined. A murine model of EPRs and LPRs was developed to investigate the role of IL-5 and eosinophils in development of both responses. After initial intraperitoneal sensitization and airway challenge to ovalbumin (OVA), mice were provoked by additional exposure to OVA. An EPR, characterized by a transient increase in airway responsiveness, was observed 5-30 minutes after antigen provocation. This response was followed by an LPR that reached its maximum at 6 hours after challenge and was characterized by increased airway responsiveness and significant lung eosinophilia. The EPR was blocked by cromoglycate and albuterol, whereas the LPR was abolished by cromoglycate and hydrocortisone. Before provocation with allergen, administration of anti-IL-5 antibody prevented the influx of eosinophils into the lung tissue and abolished the LPR but not EPR. These results suggest that IL-5 and eosinophils are essential for development of the LPR, but not EPR, in this model.

Fuzzy pattern classification of hemodynamic data can be used to determine noninvasive intracranial pressure.

OBJECTIVE: The authors previously introduced a method in which intracranial pressure (ICP) was estimated using parameters (TCD characteristics) derived from cerebral blood flow velocity (FV) and arterial blood pressure (ABP). Some results suggested that this model might be influenced by the patient's state of cerebral autoregulation and other clinical parameters. Hence, it was the aim of the present study to improve the method by modifying the previously used global procedure in certain subgroups of patients. METHODS: In 103 traumatic brain injured patients (3-76 years, mean: 31 +/- 16 years) signal data of FV, ABP and ICP were used to generate samples of TCD characteristics together with time corresponding ICP. Fuzzy Pattern Classification was used to identify cluster subsets (classes) of the sample space. On each class a local estimator of ICP was defined. This approach provides a non-invasive assessment of ICP (nICP) as follows: Using FV and ABP the TCD characteristics were computed and related to the matching classes. nICP was calculated as a weighted sum of local ICP estimations. RESULTS: ICP A and B waves and long-term trends could be visibly assessed. The median absolute difference between ICP and nICP was 5.7 mmHg. CONCLUSIONS: The class structure of the model facilitates nICP assessment in heterogeneous patient groups and supports a stepwise extension of the target patient group without affecting the former validity.