Biomarkers and longitudinal changes in lumbar spine degeneration and low back pain: the Johnston County Osteoarthritis Project.

OBJECTIVE: To determine if baseline biomarkers are associated with longitudinal changes in the worsening of disc space narrowing (DSN), vertebral osteophytes (OST), and low back pain (LBP). DESIGN: Paired baseline (2003-2004) and follow-up (2006-2010) lumbar spine radiographs from the Johnston County Osteoarthritis Project were graded for severity of DSN and OST. LBP severity was self-reported. Concentrations of analytes (cytokines, proteoglycans, and neuropeptides) were quantified by immunoassay. Pressure-pain threshold (PPT), a marker of sensitivity to pressure pain, was measured with a standard dolorimeter. Binary logistic regression models were used to estimate odd ratios (OR) and 95% confidence intervals (CI) of biomarker levels with DSN, OST, or LBP. Interactions were tested between biomarker levels and the number of affected lumbar spine levels or LBP. RESULTS: We included participants (n = 723) with biospecimens, PPT, and paired lumbar spine radiographic data. Baseline Lumican, a proteoglycan reflective of extracellular matrix changes, was associated with longitudinal changes in DSN worsening (OR = 3.19 [95% CI 1.22, 8.01]). Baseline brain-derived neuropathic factor, a neuropeptide, (OR = 1.80 [95% CI 1.03, 3.16]) was associated with longitudinal changes in OST worsening, which may reflect osteoclast genesis. Baseline hyaluronic acid (OR = 1.31 [95% CI 1.01, 1.71]), indicative of systemic inflammation, and PPT (OR = 1.56 [95% CI 1.02, 2.31]) were associated with longitudinal increases in LBP severity. CONCLUSION: These findings suggest that baseline biomarkers are associated with longitudinal changes occurring in structures of the lumbar spine (DSN vs OST). Markers of inflammation and perceived pressure pain sensitivity were associated with longitudinal worsening of LBP.

Immune cell profiling in the joint following human and murine articular fracture.

OBJECTIVE: Human and in vivo animal research implicates inflammation following articular fracture as contributing to post-traumatic arthritis. However, relevant immune cell subsets present following injury are currently undefined. Immunophenotyping human and murine synovial fluid may help to identify immune cell populations that play key roles in the response to articular fracture. METHODS: Immunophenotyping by polychromatic flow cytometry was performed on human and mouse synovial fluid following articular fracture. Specimens were collected in patients with closed ankle fracture at the time of surgical fixation and from C57BL/6 mice with closed articular knee fracture. Immune cells were collected from injured and uninjured joints in mice via a novel cell isolation method. Whole blood samples were also collected. Immunohistochemistry (IHC) was performed on mouse synovial tissue to assess for macrophages and T cells. RESULTS: Following intra-articular fracture, the prominent human synovial fluid immune cell subset was CD3+ T cells, containing both CD4+ and CD8+ T cells. In mice, infiltration of CD45+ immune cells in synovial fluid of the fractured limb was dominated by CD19+ B cells and CD3+ T cells at 7 days after intra-articular fracture. We also detected adaptive immune cells, including macrophages, NK cells, dendritic cells and monocytes. Macrophage and T cell findings were supported by IHC of murine synovial tissue. CONCLUSIONS: Determining specific cell populations that mediate the immune response is essential to elucidating the chain of events initiated after injury and may be an important step in identifying potential immune signatures predictive of PTA susceptibility or potential therapeutic targets.

Infrapatellar fat pad abnormalities are associated with a higher inflammatory synovial fluid cytokine profile in young adults following ACL tear.

OBJECTIVE: To evaluate the degree of knee fat pad abnormalities after acute anterior cruciate ligament (ACL) tear via magnetic resonance fat pad scoring and to assess cross-sectionally its association with synovial fluid biomarkers and with early cartilage damage as quantified via T1ρ and T2 relaxation time measurements. DESIGN: 26 patients with acute ACL tears underwent 3T MR scanning of the injured knee prior to ACL reconstruction. The presence and degree of abnormalities of the infrapatellar (IPFP) and the suprapatellar (SPFP) fat pads were scored on MR images along with grading of effusion-synovitis and synovial proliferations. Knee cartilage composition was assessed by 3T MR T1ρ and T2 mapping in six knee compartments. We quantified concentrations of 20 biomarkers in synovial fluid aspirated at the time of ACL reconstruction. Spearman rank partial correlations with adjustments for age and gender were employed to evaluate correlations of MR, particularly cartilage composition and fat pad abnormalities, and biomarker data. RESULTS: The degree of IPFP abnormality correlated positively with the synovial levels of the inflammatory cytokine markers IFN-γ (ρpartial = 0.64, 95% CI (0.26-0.85)), IL-10 (ρpartial = 0.47, 95% CI (0.04-0.75)), IL-6 (ρpartial = 0.56, 95% CI (0.16-0.81)), IL-8 (ρpartial = 0.49, 95% CI (0.06-0.76)), TNF-α (ρpartial = 0.55, 95% CI (0.14-0.80)) and of the chondrodestructive markers MMP-1 and -3 (MMP-1: ρpartial = 0.57, 95% CI (0.17-0.81); MMP-3: ρpartial = 0.60, 95% CI (0.21-0.83)). IPFP abnormalities were significantly associated with higher T1ρ and T2 values in the trochlear cartilage (T1ρ: ρpartial = 0.55, 95% CI (0.15-0.80); T2: ρpartial = 0.58, 95% CI (0.18-0.81)) and with higher T2 values in the medial femoral, medial tibial as well as in patellar cartilage (0.45 ≤ ρpartial ≤ 0.59). Correlations between SPFP abnormalities and synovial markers were not significant except for IL-6 (ρpartial = 0.57, 95% CI (0.17-0.81)). CONCLUSIONS: This exploratory study suggests that acute ACL rupture can be associated with damage to knee tissues such as the inferior fat pad of the knee. Such fat pad injury could be partially responsible for the apparent post-injury pro-inflammatory response noted in ACL-injured individuals. However, future longitudinal studies are needed to link ACL-rupture associated fat pad injury with important patient outcomes such as the development of posttraumatic osteoarthritis.

Conjugation of Different Immunogenic Enterococcal Vaccine Target Antigens Leads to Extended Strain Coverage.

Enterococci have emerged as important nosocomial pathogens due to their resistance to the most commonly used antibiotics. Alternative treatments or prevention options are aimed at polysaccharides and surface-related proteins that play important roles in pathogenesis. Previously, we have shown that 2 Enterococcus faecium proteins, the secreted antigen A and the peptidyl-prolyl cis-trans isomerase, as well as the Enterococcus faecalis polysaccharide diheteroglycan, are able to induce opsonic and cross-protective antibodies. Here, we evaluate the use of glycoconjugates consisting of these proteins and an enterococcal polysaccharide to develop a vaccine with broader strain coverage. Diheteroglycan was conjugated to these 2 enterococcal proteins. Rabbit sera raised against these glycoconjugates showed Immunoglobulin G titers against the corresponding conjugate, as well as against the respective protein and carbohydrate antigens. Effective opsonophagocytic killing for the 2 sera was observed against different E. faecalis and E. faecium strains. Enzyme-linked immunosorbent assays against whole bacterial cells showed immune recognition of 22 enterococcal strains by the sera. Moreover, the sera conferred protection against E. faecalis and E. faecium strains in a mouse infection model. Our results suggest that these glycoconjugates are promising candidates for vaccine formulations with a broader coverage against these nosocomial pathogens and that the evaluated proteins are potential carrier proteins.

Biomarkers of inflammation - LBP and TLR- predict progression of knee osteoarthritis in the DOXY clinical trial.

OBJECTIVE: To evaluate systemic inflammatory biomarkers in symptomatic knee osteoarthritis (OA) and their association with radiographic and biochemical OA progression. METHODS: Lipopolysaccharide (LPS) binding protein (LBP), soluble Toll-like receptor 4 (sTLR4) and interleukin 6 (IL-6) were measured in plasma of 431 knee OA patients from the doxycycline (DOXY) trial at baseline and 18 months. Plasma lipopolysaccharide and lipopolysaccharide binding protein (LBP) were also measured at 12 months. As a biochemical indicator of disease activity and OA progression, urinary (u) C-telopeptide of Type II collagen (uCTX-II) was measured in samples collected at baseline and 18 months. Change over 16 months in radiographic tibiofemoral joint space width (JSW in mm) and joint space narrowing (JSN≥0.5 mm) were used to indicate radiographic OA progression. Change over 18 months for uCTX-II was used as a secondary outcome. Both univariate and multivariable regression analyses were performed to test the association between Z-score transformed biomarkers and outcomes. RESULTS: Baseline LBP and time-integrated concentration (TIC) of LBP over 12 and 18 months were associated with worsening joint space width (JSW) (parameter estimates: -0.1 to -0.07) and JSN (OR: 1.32 to 1.42) adjusting for treatment group, age, body mass index (BMI) and corresponding baseline radiographic measures. Baseline sTLR4 and TIC over 18 months were associated with change in uCTX-II over 18 months (adjusted parameter estimates: 0.0017 to 0.0020). Results were not modified by treatment with doxycycline. CONCLUSION: Plasma LBP and sTLR4 were associated with knee OA progression over 16-18 months. These results lend further support for a role of systemic low-grade inflammation in the pathogenesis of knee OA progression.

Colchicine lack of effectiveness in symptom and inflammation modification in knee osteoarthritis (COLKOA): a randomized controlled trial.

OBJECTIVES: Uric acid may activate an innate immune response in osteoarthritis (OA), contributing to disease pathology and progression. We evaluated the effectiveness of colchicine on pain and function in symptomatic knee OA (KOA) and the underlying mechanism of action. METHODS: Colchicine effectiveness in symptoms and inflammation modification in knee osteoarthritis (COLKOA) was a double-blind, placebo-controlled, randomized trial comparing 16 weeks of treatment with 0.5 mg twice-daily oral colchicine to placebo for knee osteoarthritis (KOA). The primary endpoint was ≥30% improvement in total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score at week 16. Secondary endpoints included improvement in pain (0-10 Likert scales); WOMAC pain; patient global assessment (0-100); physical function; the OARSI-OMERACT response; quality of life; and change in serum, urine, synovial fluid (SF) biomarkers of cartilage metabolism and inflammation, and plasma/SF colchicine concentrations. RESULTS: Of 109 randomly assigned participants, 39% (95% confidence interval (CI) 27-52%) and 49% (95% CI 36-62%) in the colchicine and placebo arms respectively met the primary endpoint at study end (P = 0.284, odds ratio 0.66, 95% CI 0.31-1.41). No strong evidence of treatment differences was identified on clinical secondary endpoints. Treatment significantly reduced mean serum hs-CRP (P = 0.008) and SF CTXI (P = 0.002); treatment tended to reduce inflammatory markers (SF IL-6, IL8, TNFα, CD14 and IL-18), but these differences were not statistically significant. CONCLUSION: Colchicine (0.5 mg twice-daily orally) reduced inflammation and high bone turnover biomarkers known to be associated with OA severity and progression risk, but did not reduce KOA symptoms over a 16-week study period. A longer-term study to evaluate for slow-acting disease modifying effects is warranted. TRIAL REGISTRATION: The trial has been registered at clinicaltrials.gov as NCT02176460. Date of registration: June 26, 2014.

Nutrition care of cancer patients-A survey among physicians and nurses.

In order to quantify gaps in the provision of medical nutrition care in Germany and pinpoint specific areas of need, we collected data from patients, nurses and physicians. The results from the patient survey were published separately. A total of 506 participants from 69 certified centers answered the questions developed in cooperation with representatives from different professional groups (physicians, nurses and dietitians). Only about a third of participants reported that their institution provides structured pathways to nutritional counseling. 70.1% of those physicians reported that there was a specialist in nutrition available at their center while only 55.8% of nurses agreed. Only a quarter (24.2% and 26.9%) of physicians and nurses reported that their institution provided continuation of nutrition care after dismissal. A gap exists between need and consistent delivery of nutrition care services. Structured nutrition care pathways provided by legally certified nutrition professionals pathways are lacking. Cancer organizations may support this process by requiring documented nutrition care pathways and provision of services on a need based system into guidelines and certification criteria.

Synovial fluid pro-inflammatory profile differs according to the characteristics of knee pain.

OBJECTIVE: The role of inflammation and pain in osteoarthritis (OA) is not fully understood. We evaluated the association between pro-inflammatory biomarkers and pain. METHODS: We used baseline data and samples from a randomized controlled trial of colchicine for symptomatic knee OA. Severity of pain of the more symptomatic knee was assessed by National Health and Nutrition Examination Survey-I (NHANES-I) criterion and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain index. Pains on movement and at rest were self-reported on an 11-point Likert scale. Severity of radiographic tibiofemoral OA was assessed by Kellgren and Lawrence (KL) grade. Concentrations of synovial fluid (sf) IL-1ß, IL-6, IL-8, TNFα, C-terminal telopeptides of Type I collagen (CTXI) and C-telopeptide of Type II collagen (CTXII), as well as urinary (u) CTXII were measured. RESULTS: Of the 109 patients enrolled in the study, 70 patients (70% women) with synovial fluid obtained by direct aspiration were included for analysis. The mean ± SD age and body mass index (BMI) of the patients were 57.6 ± 8.3 years and 28.8 ± 5.2 kg/m2. After adjustment for age, sex, and BMI, sf IL-6 and IL-8 were statistically significantly associated with 11-point pain on movement, but not with pain at rest. No significant associations were observed with WOMAC pain scores. sf IL-1ß (analyzed as detectable/non-detectable) was inversely associated with pain. In contrast, after adjustment, Sf TNFα was associated with WOMAC total pain and both pain on movement and at rest. sf/u CTXII was associated with radiographic severity, but not with knee pain. CONCLUSIONS: This study provides indication that OA pain mechanisms may differ according to the characteristics of the pain.

Pain prediction by serum biomarkers of bone turnover in people with knee osteoarthritis: an observational study of TRAcP5b and cathepsin K in OA.

OBJECTIVES: To investigate serum biomarkers, tartrate resistant acid phosphatase 5b (TRAcP5b) and cathepsin K (cath-K), indicative of osteoclastic bone resorption, and their relationship to pain and pain change in knee osteoarthritis (OA). METHODS: Sera and clinical data were collected from 129 people (97 with 3-year follow-up) with knee OA from the Prediction of Osteoarthritis Progression (POP) cohort. Knee OA-related outcomes in POP included: WOMAC pain, National Health and Nutrition Examination Survey (NHANES) I (pain, aching and stiffness), subchondral sclerosis, and radiographically determined tibiofemoral and patellofemoral OA. Two putative osteoclast biomarkers were measured in sera: TRAcP5b and cath-K. Medial tibia plateaux were donated at knee arthroplasty for symptomatic OA (n = 84) or from 16 post mortem (PM) controls from the Arthritis Research UK (ARUK) Pain Centre joint tissue repository. Osteoclasts were stained for tartrate resistant acid phosphatase (TRAcP) within the subchondral bone of the medial tibia plateaux. RESULTS: Serum TRAcP5b activity, but not cath-K-immunoreactivity, was associated with density of TRAcP-positive osteoclasts in the subchondral bone of medial tibia plateaux. TRAcP-positive osteoclasts were more abundant in people with symptomatic OA compared to controls. Serum TRAcP5b activity was associated with baseline pain and pain change. CONCLUSIONS: Our observations support a role for subchondral osteoclast activity in the generation of OA pain. Serum TRAcP5b might be a clinically relevant biomarker of disease activity in OA.

Nutritional care of cancer patients: a survey on patients' needs and medical care in reality.

PURPOSE: Cancer patients represent a patient group with a wide-range of nutrition related problems which are often under-recognized and undertreated. In order to assess the status quo of nutritional care in Germany, we conducted a survey among patients with different types of cancer. METHODS: A standardized questionnaire was distributed online by two national umbrella organizations for self-help groups. RESULTS: 1335 participants completed the questionnaire. 69 % of the participants reported having received information on nutrition and/or specific nutrition-related symptoms. Most often this information was derived from print media (68.5 %) or from within self-help groups (58.7 %). 57.0 % of participants reported having had questions concerning nutrition and/or problems with food intake. most frequently named topics of interest were "healthy diet" (35.0 %) weakness/fatigue (24.3 %), dietary supplements (21.3 %) and taste changes (19.8 %). Nutrition information was most often provided by dietitians (38.7 %) followed by physicians (9.8 %). Women reported receiving nutrition counseling in the hospital nearly twice as often as men (12.5 % versus 5.7 %; p < 0.001). A quarter of the patients (24.1 %) reported using dietary supplements and patients who had received some sort of nutrition information more often reported using supplements (p < 0.001). CONCLUSION: Nutrition is an essential element in cancer care and patients report a high interest and need: Yet, many patients do not have access to high quality nutrition therapy during and after cancer therapy. IMPLICATIONS FOR CANCER SURVIVORS: With respect to survival and quality of life, increasing the availability and resources for provision of evidence based nutrition information seems mandatory.

Exploratory secondary analyses of a cognitive-behavioral intervention for knee osteoarthritis demonstrate reduction in biomarkers of adipocyte inflammation.

OBJECTIVE: To investigate the effects of pain coping skills training (PCST) and a lifestyle behavioral weight management (BWM) program on inflammatory markers and biomarker associations with pain and function in the OA LIFE study. METHOD: Serum samples were available from a subset (N = 169) of the overweight or obese knee OA participants in the OA LIFE study that evaluated: PCST, BWM, combined PCST + BWM, or standard care (SC). Inflammatory markers (hsCRP, IL-1ra, IL-1ß, IL-6, IL-8, TNF-α, TNFRI, TNFRII, and hyaluronic acid (HA)), and adipokines (leptin and adiponectin) were measured before and after the 24-week treatment period. Biomarkers were assessed for effects of treatment and for associations with change in weight, pain and disability (unadjusted and adjusted for age, race, sex, baseline body mass index (BMI), and baseline biomarker concentration). RESULTS: PCST + BWM was associated with significant reductions in hsCRP (P = 0.0014), IL-6 (P = 0.0075), and leptin (P = 0.0001). After adjustment, there was a significant effect of PCST + BWM on changes in leptin (b = -0.19, P = 0.01) and IL-6 (b = -0.25, P = 0.02) relative to SC. Reductions in leptin and IL-6 were significantly correlated with reductions in weight, BMI and Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain; reductions in IL-6 were correlated with improvements in WOMAC and Arthritis Impact Measurement Scales (AIMS) physical function. By mediation analyses, weight loss was responsible for 54% of the change in IL-6 and all of the change in leptin. CONCLUSIONS: OA-related inflammatory markers were reduced by a 24-week combined PCST + BWM intervention. This suggests that the inflammatory state can be successfully modified in the context of a readily instituted clinical intervention with a positive clinical outcome.

Direct in vivo evidence of activated macrophages in human osteoarthritis.

OBJECTIVE: Through binding to folate receptor-ß (FR-ß), the new (99m)Tc-EC20 (Etarfolatide) imaging technique detects activated but not resting macrophages in vivo. The goal of this study was to investigate macrophage-related inflammation in osteoarthritis (OA). METHODS: Twenty-five individuals (50 knees) with symptomatic OA of at least one knee underwent SPECT-CT imaging of both knees and planar imaging of the whole body after injection of Etarfolatide. Scans and knee radiographs were scored blinded to clinical information including knee and other joint site pain severity. Measures of association controlled for age, gender, body mass index (BMI) and employed repeated measures to adjust for correlation between knees. DESIGN: Activated macrophages were present in the majority (76%) of knees. The quantity of knee-related macrophages was significantly associated with knee pain severity (R = 0.60, P < 0.0001) and radiographic knee OA severity including joint space narrowing (R = 0.68, P = 0.007), and osteophyte (R = 0.66, P = 0.001). Macrophages were also localized to joints commonly affected by OA including hand finger joints (12%), thumb bases (28%), shoulders (26%), great toes (18%) and ankles (12%). The presence of joint pain at fingers, wrists, ankles and great toes was significantly positively associated with presence of activated macrophages at these sites (P < 0.0001-0.04). CONCLUSIONS: This study provides the first direct in vivo evidence for macrophage involvement in OA in a substantial proportion of human knees. The association of quantity of activated macrophages with radiographic knee OA severity and joint symptoms suggests that drugs targeting macrophages and macrophage-associated inflammatory pathways may have the potential to be both symptom and structure modifying.

Information needs of oncologists, general practitioners and other professionals caring for patients with cancer.

Oncology is a rapidly developing field with a growing number of publications every year. The main goal of this survey was to learn more about the information needs of oncologists and general practitioners. Data were collected using a standardised questionnaire developed in collaboration with the German Cancer Society (Deutsche Krebsgesellschaft) and the German Association of General Practitioners (Deutscher Hausärzteverband). A total of 495 questionnaires could be evaluated. Medical congresses were the preferred source of information for all participants. General practitioners preferred textbooks, while oncologists preferred journals and the Internet (all p < .001). Reasons for a lack of confidence during patient consultation were lack of time (60% of participants), lack of knowledge (61% of general practitioners and 26% of oncologists) and lack of data (>50%). Oncologists felt more confident in searching scientific databases than general practitioners did. Both groups required rapid access to transparent information. For general practitioners, reviews and comments by experts helped to put new information in the context of cancer treatment. Oncologists and general practitioners showed significantly different information needs and different ways to access specific information. In order to better integrate general practitioners while simultaneously serving the needs of oncologists, a database that is up to date, rapidly accessible and does not incur high costs would be helpful.

Information Needs of Cancer Patients and Perception of Impact of the Disease, of Self-Efficacy, and Locus of Control.

The aim of our study was to investigate the relationship between information needs and cancer patients' perceptions of the impact of the disease, self-efficacy, and locus of control. Using a standardized questionnaire, we obtained data from patients who attended a series of lectures. The questionnaire included questions on their information needs, sources of information, satisfaction with information, and short questionnaires on self-efficacy, perception of the disease, and locus of control of reinforcement. Data was obtained from 185 patients. Our results showed that the sources of information that were most often used were physicians (84 %), print media (68 %), and the Internet (59 %); online fora (7.5 %), non-medical practitioners (9.7 %), and telephone-based counseling (8.6 %) were only used by a minority. Patients with a high perception of their own control over the disease more often used any source of information available to them and were more often interested in acquiring additional information. Higher self-efficacy was significantly associated with the need for information on all topics. Patients with a higher external locus of control significantly more often used sources of information and had significantly more need for additional information. By contrast, there were no associations with an internal locus of control. Neither external nor internal locus of control showed any associations with satisfaction with information. Information needs seem to be higher in patients with a high external locus of control and low self-efficacy. Physicians, other professionals, and institutions that provide information may take these relationships into consideration for tailoring their services to patients.

Distinct SagA from Hospital-Associated Clade A1 Enterococcus faecium Strains Contributes to Biofilm Formation.

Enterococcus faecium is an important nosocomial pathogen causing biofilm-mediated infections. Elucidation of E. faecium biofilm pathogenesis is pivotal for the development of new strategies to treat these infections. In several bacteria, extracellular DNA (eDNA) and proteins act as matrix components contributing to biofilm development. In this study, we investigated biofilm formation capacity and the roles of eDNA and secreted proteins for 83 E. faecium strains with different phylogenetic origins that clustered in clade A1 and clade B. Although there was no significant difference in biofilm formation between E. faecium strains from these two clades, the addition of DNase I or proteinase K to biofilms demonstrated that eDNA is essential for biofilm formation in most E. faecium strains, whereas proteolysis impacted primarily biofilms of E. faecium clade A1 strains. Secreted antigen A (SagA) was the most abundant protein in biofilms from E. faecium clade A1 and B strains, although its localization differed between the two groups. sagA was present in all sequenced E. faecium strains, with a consistent difference in the repeat region between the clades, which correlated with the susceptibility of biofilms to proteinase K. This indicates an association between the SagA variable repeat profile and the localization and contribution of SagA in E. faecium biofilms.

Sustained intra-articular delivery of IL-1RA from a thermally-responsive elastin-like polypeptide as a therapy for post-traumatic arthritis.

Post-traumatic arthritis (PTA) is a rapidly progressive form of arthritis that develops due to joint injury, including articular fracture. Current treatments are limited to surgical restoration and stabilization of the joint; however, evidence suggests that PTA progression is mediated by the upregulation of pro-inflammatory cytokines, such as interleukin-1 (IL-1) or tumor necrosis factor-α (TNF-α). Although these cytokines provide potential therapeutic targets for PTA, intra-articular injections of anti-cytokine therapies have proven difficult due to rapid clearance from the joint space. In this study, we examined the ability of a cross-linked elastin-like polypeptide (xELP) drug depot to provide sustained intra-articular delivery of IL-1 and TNF-α inhibitors as a beneficial therapy. Mice sustained a closed intra-articular tibial plateau fracture; treatment groups received a single intra-articular injection of drug encapsulated in xELP. Arthritic changes were assessed 4 and 8 weeks after fracture. Inhibition of IL-1 significantly reduced the severity of cartilage degeneration and synovitis. Inhibition of TNF-α alone or with IL-1 led to deleterious effects in bone morphology, articular cartilage degeneration, and synovitis. These findings suggest that IL-1 plays a critical role in the pathogenesis of PTA following articular fracture, and sustained intra-articular cytokine inhibition may provide a therapeutic approach for reducing or preventing joint degeneration following trauma.

In vitro and in vivo activity of hyperimmune globulin preparations against multiresistant nosocomial pathogens.

PURPOSE: We compared different immunoglobulin preparations containing IgG (Intraglobin/Intratect) or a mixture of IgG, IgA, and IgM (Pentaglobin) to assess the opsonic and protective efficacy of human immunoglobulin preparations against multiresistent nosocomial pathogens. MATERIALS AND METHODS: Clinical isolates of E. coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecalis, Enterococcus faecium, and Staphylococcus aureus were tested by opsonophagocytic assay using immunologobulin preparations at dilutions usually obtained in patients. The target antigens of opsonic antibodies were characterized by opsonophagocytic inhibition assays, and the protective efficacy in vivo was tested in a mouse bacteremia model as previously described. RESULTS: All strains were killed to at least 50% by Pentaglobin. One P. aeruginosa strain was not efficiently killed by Intraglobin (23%) but the other strains were killed by Intraglobin to a similar degree compared to Pentaglobin. Opsonic IgG antibodies against E. faecalis were directed against LTA, while opsonic antibodies in Pentaglobin were primarily directed against other cell wall carbohydrates. In a mouse bacteremia model, Pentaglobin was more protective than Intratect against Staphylococcus aureus, while Intratect reduced colony counts better than normal rabbit serum or saline. CONCLUSIONS: All tested human immunoglobulin preparations contain opsonic and protective antibodies against targets present on multiresistant Gram-positive and Gram-negative bacteria. Enrichment of these preparations with IgM increases the protective efficacy against some strains, probably due to antibodies directed against cell wall carbohydrates.

A lecture program on complementary and alternative medicine for cancer patients--evaluation of the pilot phase.

About half of all patients with cancer use complementary or alternative medicine (CAM). In 2013, we started a lecture program for patients, followed by evidence-based recommendations on counseling on CAM. These recommendations have been published before by this working group. The aim of the program is to provide scientific facts on the most often used CAM methods in standardized presentations which help patients discuss the topic with their oncologists and support shared decision making. The article presents the evaluation of the pilot phase. Participants received a standardized questionnaire before the start of the lecture. The questionnaire comprises four parts: demographic data, data concerning experience with CAM, satisfaction with the lecture, and needs for further information on CAM. In 2013, seven lectures on CAM were given in cooperation with regional branches of the German Cancer Society in several German states. Four hundred sixty patients and relatives took part (75% females and 16% males). Forty-eight percent formerly had used CAM. Most often named sources of information on CAM were print media (48%) and the Internet (37%). Most participants rated additional written information valuable. About one third would like to have an individual consultation concerning CAM. A standardized presentation of evidence on CAM methods most often used, together with recommendations on the self-management of symptoms, is highly appreciated. The concept of a highly interactive lecture comprising is feasible and if presented in lay terminology, adequate. In order to give additional support on the topic, written information should be provided as the first step.

Detection of opsonic antibodies against Enterococcus faecalis cell wall carbohydrates in immune globulin preparations.

Three different commercially available polyvalent immune globulins (IG) were investigated for the existence of antibodies against cell wall carbohydrates of four different E. faecalis serotypes (using a cell wall carbohydrate-enzyme-linked immunosorbent assay), and whether these antibodies mediated opsonic killing (using an opsonic-killing assay). All three IG preparations contained antibodies against all four serotypes (CPS-A to CPS-D). However, only one of the three IG preparations showed opsonic killing against all four serotypes. Average killing was higher against serotypes A and B (72 and 79 %, respectively) than against serotypes C and D (30 and 37 %, respectively). Such IG preparations could play a role as an adjuvant therapeutic option in life-threatening infections with E. faecalis, particularly when resistant strains are involved.

Integrating cancer patients' perspectives into treatment decisions and treatment evaluation using patient-reported outcomes--a concept paper.

Patient-reported outcomes are an important tool in clinical research. In the setting of cancer treatments, benefit of therapy is essentially characterised by improvement of survival as well as quality of life (QoL). A standardised instrument to assess QoL is the standardised QoL questionnaire of the European Organisation for Research and Treatment (EORTC QLQ-C30 questionnaire). QoL instruments provide data on different aspects (domains) of the framework of QoL. Using these questionnaires in studies provides data on how a treatment affects QoL in a group of patients. The goal of our concept is to individualise QoL and to use validated instruments in order to integrate patients' perspectives and aims into treatment assessment, planning and control. We propose to use the domains of the EORTC QLQ-C30 and to ask the patient to determine which objectives besides survival are relevant for him and should be achieved by treatment. These individual goals can be used in a process of shared decision-making to choose and monitor treatment. In clinical studies, this approach would allow to recruit more patients who would most probably benefit from the therapy. In addition, supportive data could be gathered in correlation to treatment goals and actual benefits.