Search

Purpose: Multiple myeloma is a largely incurable disease. Patients suffer from the cancer, therapeutic side effects, and often psychological symptoms. Not only multiple myeloma patients but also patients with precursor diseases show high psychological distress. Today, treatment option evaluations are increasingly performed in combination with health-related quality of life (HRQoL) assessments. One factor that is positively associated with HRQoL is social support. Methods: Our recent study used questionnaires (EORTC QLQ-C30, EORTC QLQ-MY20, Illness-specific Social Support Scale) to investigate the influence of positive and negative aspects of social support on HRQoL in patients with multiple myeloma and its precursors. Results: Multiple linear regression analyses with sex, age, treatment line, hemoglobin level, and number of comorbidities as control variables show that positive social support had a significant beneficial association with emotional function (β = 0.323) and social function (β = 0.251). Detrimental interactions had a significant negative association with social function (β = − 0.209) and a significant positive association with side effects of treatment (β = 0.266). Conclusion: Therefore, screening for social support and, if needed, psycho-oncological care can be an important resource and should be implemented in routine care. Clinical trial registration: This study was registered with clinicaltrials.gov (NCT04328038). [ABSTRACT FROM AUTHOR]

Objectives: Aim of this study was to retrospectively evaluate an interdisciplinary consultation followed by a precision‐based exercise program (PEP) for myeloma patients with stable and unstable bone lesions. Methods: Data of myeloma patients (n = 100) who received a PEP according to an orthopedic evaluation were analyzed. Bone stability was assessed by established scoring systems (Spinal Instability Neoplastic Score [SINS], Mirels' score). All patients with stable and unstable osteolyses received a PEP and n = 91 were contacted for a follow‐up interview. Results: In 60% of patients at least one osteolysis of the spine was considered potentially unstable or unstable. Following consultation, the number of patients performing resistance training could be significantly increased (≥2 sessions/week, 55%). Musculoskeletal pain was reported frequently. At the follow‐up interview, 75% of patients who performed PEP stated that painful symptoms could be effectively alleviated by exercise. Moreover, only patients who exercised regularly discontinued pain medication. No injuries were reported in association with PEP. Conclusion: We were able to demonstrate that individualized resistance training is implementable and safe for myeloma patients. By means of a PEP, patients' self‐efficacy in managing musculoskeletal pain was enhanced and pain medication could be reduced. [ABSTRACT FROM AUTHOR]

Purpose: This in vitro study was designed to determine if standard antiseptics used for skin and environmental surface cleansing can disrupt the metabolic activity (as a measure of viability) of multidrug-resistant gram-negative bacteria, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus isolates within their native biofilms. Methods: Sixty clinical isolates of multidrug-resistant bacteria were selected for testing in different chlorhexidine gluconate, octenidine, polyhexanide and chloroxylenol concentrations. Metabolic inhibition of biofilm for each clinical isolate was analysed using a biofilm viability assay. Results: Chlorhexidine gluconate (mean = 83.8% ± 9.8%) and octenidine (mean = 84.5% ± 6.8%) showed the greatest efficacy against biofilms of the tested microorganisms, with the greatest efficacies against MRSA. The antiseptics demonstrated the least efficacy against biofilms of Pseudomonas aeruginosa. Conclusion: Chlorhexidine gluconate and octenidine showed the greatest level of bacterial metabolic inhibition and were statistically equivalent. Polyhexanide was more effective than chloroxylenol, but both were inferior to chlorhexidine gluconate and octenidine against the tested organisms. [ABSTRACT FROM AUTHOR]

Purpose: Aseptic implant loosening is still a feared complication in the field of orthopaedics. Presumably, a chronic inflammatory response is induced by wear particles, which leads to osteoclast generation, bone degradation and hence loosening of the implant. Since it has been demonstrated in the literature that most implants are in fact colonized by bacteria, the question arises whether aseptic implant loosening is truly aseptic. The aim of this study was to investigate a possibly enhanced inflammatory response to metal wear particles in the context of subclinical infection.Patients and Methods: Tissue samples were collected intra-operatively from patients undergoing implant-exchange surgery due to aseptic loosening. Histopathological analysis was performed, as well as gene expression analysis for the pro-inflammatory cytokine Interleukin-8. By a series of in vitro experiments, the effect of metal wear particles on human monocytes, polymorphonuclear neutrophiles and osteoblasts was investigated. Additionally, minor amounts of lipoteichoic acid (LTA) and the bacterial heat shock protein GroEL were added.Results: Histopathology of tissue samples revealed an accumulation of metal wear particles, as well as a cellular infiltrate consisting predominately of mononuclear cells. Furthermore, high expression of IL-8 could be detected in tissue surrounding the implant. Monocytes and osteoblasts in particular showed an increased release of IL-8 after stimulation with metal wear particles and in particular after stimulation with bacterial components and wear particles together.Conclusion: We were able to show that minor amounts of bacterial components and metal wear particles together induce an enhanced inflammatory response in human monocytes and osteoblasts. This effect could significantly contribute to the generation of bone-resorbing osteoclasts and hence implant-loosening. [ABSTRACT FROM AUTHOR]

Background: Implant-associated infections are still a feared complication in the field of orthopedics. Bacteria attach to the implant surface and form so-called biofilm colonies that are often difficult to diagnose and treat. Since the majority of studies focus on prosthetic joint infections (PJIs) of the hip and knee, current treatment options (eg, antibiotic prophylaxis) of implant-associated infections have mostly been adapted according to these results.Objective: The aim of this study was to evaluate patients with surgical site infections following instrumented stabilization of the spine with regard to detected bacteria species and the course of the disease.Patients and Methods: We performed a retrospective single-center analysis of implant-associated infections of the spine from 2010 to 2014. A total of 138 patients were included in the study. The following parameters were evaluated: C-reactive protein serum concentration, microbiological evaluation of tissue samples, the time course of the disease, indication for instrumented stabilization of the spine, localization of the infection, and the number of revision surgeries required until cessation of symptoms.Results: Coagulase-negative Staphylococcus spp. were most commonly detected (n=69, 50%), followed by fecal bacteria (n=46, 33.3%). In 23.2% of cases, no bacteria were detected despite clinical suspicion of an infection. Most patients suffered from degenerative spine disorders (44.9%), followed by spinal fractures (23.9%), non-degenerative scoliosis (20.3%), and spinal tumors (10.1%). Surgical site infections occurred predominantly within 3 months (64.5%), late infections after 2 years were rare (4.3%), in particular when compared with PJIs. Most cases were successfully treated after 1 revision surgery (60.9%), but there were significant differences between bacteria species. Fecal bacteria were more difficult to treat and often required more than 1 revision surgery.Conclusion: In summary, we were able to demonstrate significant differences between spinal implant-associated infections and PJIs. These aspects should be considered early on in the treatment of surgical site infections following instrumented stabilization of the spine. [ABSTRACT FROM AUTHOR]

Background. Streptococci are not an infrequent cause of periprosthetic joint infection (PJI). Management by debridement, antibiotics, and implant retention (DAIR) is thought to produce a good prognosis, but little is known about the real likelihood of success. Methods. A retrospective, observational, multicenter, international study was performed during 2003–2012. Eligible patients had a streptococcal PJI that was managed with DAIR. The primary endpoint was failure, defined as death related to infection, relapse/persistence of infection, or the need for salvage therapy. Results. Overall, 462 cases were included (median age 72 years, 50% men). The most frequent species was Streptococcus agalactiae (34%), and 52% of all cases were hematogenous. Antibiotic treatment was primarily using β-lactams, and 37% of patients received rifampin. Outcomes were evaluable in 444 patients: failure occurred in 187 (42.1%; 95% confidence interval, 37.5%–46.7%) after a median of 62 days from debridement; patients without failure were followed up for a median of 802 days. Independent predictors (hazard ratios) of failure were rheumatoid arthritis (2.36), late post-surgical infection (2.20), and bacteremia (1.69). Independent predictors of success were exchange of removable components (0.60), early use of rifampin (0.98 per day of treatment within the first 30 days), and long treatments (≥21 days) with β-lactams, either as monotherapy (0.48) or in combination with rifampin (0.34). Conclusions. This is the largest series to our knowledge of streptococcal PJI managed by DAIR, showing a worse prognosis than previously reported. The beneficial effects of exchanging the removable components and of β-lactams are confirmed and maybe also a potential benefit from adding rifampin. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate bacteria species detected in a large number of patients treated for prosthetic joint infection of the hip and knee at a single specialized center. Furthermore, the rate of implant loosening was investigated in a time-dependent manner for the most frequently detected bacteria species. A retrospective analysis of patients (n = 209) treated for prosthetic joint infection of the hip and knee was performed. The following parameters were evaluated: C-Reactive Protein (CRP) concentration, microbiological evaluation of tissue samples, loosening of the implant, the time that had elapsed since the primary prosthetic joint replacement, and the duration since the last surgical intervention. Coagulase-negative Staphylococcus spp. were most frequently detected, followed by Staphylococcus aureus. Differences in CRP concentration were detected among various bacteria species. Osteolysis was not associated with one causative agent in particular. Patients who had undergone previous revision surgery had a higher probability of implant loosening. Coagulase-negative Staphylococcus spp. are the most common causative agents of prosthetic joint infection and show no significant differences with regard to implant loosening or the time-course when compared to S. aureus. Infections with Enterococcus spp. seem to develop faster than with other bacteria species. The risk of implant loosening increases with revision surgery, in particular in the hip joint. [ABSTRACT FROM AUTHOR]

Introduction: Osteitis is one of the most serious complications in orthopedic surgery. Expert Tibia Nail (ETN) PROtect™ coated with a biodegradable layer of gentamicin-laden polymer was developed for prophylaxis of osteomyelitis. In systemic administration, gentamicin has only a small therapeutic index and serious side effects; it is potentially nephrotoxic as well as ototoxic. It is not yet known if relevant gentamicin concentrations are released into the systemic circulation after implantation of gentamicin-coated nails. In order to evaluate the patients' risks profiles and increase patient safety, we measured gentamicin levels in pre- and postoperative serum samples of patients undergoing implantation of ETN PROtect.Methods: Twenty-five patients who received ETN PROtect between March 2012 and August 2014 were included in this study. Collection of blood samples occurred before the operation, at weeks 1-4, 3 and 6 months, and up to 1 year after the implantation. Measurement of gentamicin levels in serum samples was performed at the central laboratory of Heidelberg University Hospital. Additionally, laboratory parameters, C-reactive protein, leukocyte number, urea and creatinine concentrations were analyzed in routine controls before and after operating and assessed for systemic side effects.Results: Over the course of this prospective observational study, we were able to determine that gentamicin-coated nails do not release gentamicin into the systemic circulation above the lowest detectable level of 0.2 mg/dL. There were slight increases in the mean inflammation and renal retention markers, but no gentamicin-associated side effects could be linked to implantation. Furthermore, no allergic reactions could be detected during our study.Conclusion: Our findings suggest that there is no relevant release of gentamicin into the systemic circulation causing a systemic effect, and serious side effects due to gentamicin-coated tibia nails should not be feared. Postoperative monitoring of renal function does not seem necessary because of the implantation of ETN PROtect. [ABSTRACT FROM AUTHOR]

The recognition and phagocytosis of free-swimming (planktonic) bacteria by polymorphonuclear neutrophils have been investigated in depth. However, less is known about the neutrophil response towards bacterial biofilms. Our previous work demonstrated that neutrophils recognize activating entities within the extracellular polymeric substance (EPS) of biofilms (the bacterial heat shock protein GroEL) and that this process does not require opsonization. Aim of this study was to evaluate the release of DNA by neutrophils in response to biofilms, as well as the release of the inflammatory cytokine MRP-14. Neutrophils were stimulated with Staphylococcus epidermidis biofilms, planktonic bacteria, extracted EPS and GroEL. Release of DNA and of MRP-14 was evaluated. Furthermore, tissue samples from patients suffering from biofilm infections were collected and evaluated by histology. MRP-14 concentration in blood samples was measured. We were able to show that biofilms, the EPS and GroEL induce DNA release. MRP-14 was only released after stimulation with EPS, not GroEL. Histology of tissue samples revealed MRP-14 positive cells in association with neutrophil infiltration and MRP-14 concentration was elevated in blood samples of patients suffering from biofilm infections. Our data demonstrate that neutrophil-activating entities are present in the EPS and that GroEL induces DNA release by neutrophils. [ABSTRACT FROM AUTHOR]

Background: Implant infections are a major complication in the field of orthopaedics. Bacteria attach to the implant-surface and form biofilm-colonies which makes them difficult to treat. Not only immune cells exclusively respond to bacterial challenges, but also local tissue cells are capable of participating in defense mechanisms. The aim of this study was to evaluate the role of osteoblasts in the context of implant infections.Methods: Primary osteoblasts were cultivated and stimulated with free-swimming bacteria at 4 °C and 37 °C. Supernatants were harvested for ELISA and expression of pro-inflammatory cytokines evaluated by RT-PCR. Bacterial binding to osteoblasts was evaluated using cytofluorometry and uptake was investigated by (3)H thymidine-labelling of bacteria. Osteoblasts were additionally stimulated with the extracellular polymeric substance (EPS) of Staphylococcus epidermidis biofilms, as well as components of the EPS; the bacterial heat shock protein GroEL in particular.Results: We demonstrated that binding of bacteria to the osteoblast cell surface leads to an increased production of pro-inflammatory cytokines. Bacteria are capable of surviving intracellular. Furthermore, osteoblasts do not only respond to free-swimming, planktonic bacteria, but also to components of the EPS, including lipoteichoic acid and the heat shock protein GroEL.Conclusion: In conclusion, local tissue cells, specifically osteoblasts, might contribute to the persistence of the inflammatory response associated with implant-infections. [ABSTRACT FROM AUTHOR]

Impaired fracture healing, especially when associated with bacterial infection, is a severe complication following long-bone fractures and requires special treatment. Because standard diagnostic techniques might provide falsely negative results, we evaluated the sonication method for detection of bacteria on implants of patients with fracture nonunions. A total of 49 patients with a nonunion (group NU) and, for comparison, 45 patients who had undergone routine removal of osteosynthetic material (group OM), were included in the study. Five different diagnostic methods (culture of tissue samples, culture of intraoperative swabs, histopathology of tissue samples, culture of sonication fluid, and 16S ribosomal DNA polymerase chain reaction of sonication fluid) were compared and related to clinical data. Among the diagnostic tests, culture of sonication fluid demonstrated by far the highest detection rate of bacteria (57%) in group NU, and rather unexpectedly 40% in group OM. Culture of sonication samples also revealed a broad spectrum of bacteria, in particular Propionibacterium spp. In conclusion, our results indicate that more bacteria can be detected on implants of patients with atrophic nonunions of long-bone fractures by means of the sonication procedure, which provides a valuable additional diagnostic tool to decide on a surgical procedure (eg, two-step procedure) and to further specify antimicrobial therapy. [ABSTRACT FROM AUTHOR]

Infections of implants pose a severe problem in the field of orthopedic surgery, because they can cause bone degradation with subsequent loosening of the implant. The discrimination between septic implant loosening and aseptic loosening can be a challenge, and hence novel diagnostic methods have been introduced to improve the detection of bacteria. Because a major problem is their firm adherence to implants due to biofilm formation, sonication has been introduced, followed by identification of bacteria by culture or genetic methods. In this study, we compared the results obtained after sonication pretreatment with those of microbiological testing of tissue samples and histopathological evaluation of the same tissue. Furthermore, we related the results obtained following sonication to the clinical diagnosis of septic or aseptic implant loosening, respectively. Sonication of explanted devices also enhances the likelihood of detecting bacterial growth in patients who were considered "aseptic" based on the clinical evaluation. [ABSTRACT FROM AUTHOR]

Purpose: Loosening of implants occurs mainly for two reasons: bacterial infection of the implant or 'aseptic loosening' presumably due to wear particles derived from the implant. To gain further insight into the pathomechanism, we analysed activation of the T cell response in these patients. Methods: Activation of peripheral T lymphocytes was determined by cytofluorometry as down-regulation of CD28 and up-regulation of CD11b. In addition, tissue samples obtained during surgery were analysed by quantitative RT-PCR for gene expression of CD3, CD14 and cathepsin K, as markers for T cells, monocytes/macrophages or osteoclasts, respectively. Results: Activated T lymphocytes were detected in patients with infection but not in patients with aseptic loosening. Gene expression of CD3 was significantly enhanced in tissues of patients with infection compared to those with aseptic loosening. Expression of CD14 and of cathepsin K did not differ between the two groups. Conclusion: Implant-associated infection and aseptic loosening are associated with a local inflammatory response, which eventually results in osteoclastogenesis and bone resorption. Systemic T cell activation, in contrast, occurs only in patients with implant-associated infection, and hence analysis of T cell activation markers could serve as a diagnostic tool to differentiate between the two entities. [ABSTRACT FROM AUTHOR]

Background Metal-on-metal implants are a special form of hip endoprostheses that despite many advantages can entail serious complications due to release of wear particles from the implanted material. Metal wear particles presumably activate local host defence mechanisms, which causes a persistent inflammatory response with destruction of bone followed by a loosening of the implant. To better characterize this inflammatory response and to link inflammation to bone degradation, the local generation of proinflammatory and osteoclastinducing cytokines was analysed, as was systemic T cell activation. Methods By quantitative RT-PCR, gene expression of cytokines and markers for T lymphocytes, monocytes/macrophages and osteoclasts, respectively, was analysed in tissue samples obtained intraoperatively during exchange surgery of the loosened implant. Peripheral T cells were characterized by cytofluorometry before surgery and 7 to 10 days thereafter. Results At sites of osteolysis, gene expression of cathepsin K, CD14 and CD3 was seen, indicating the generation of osteoclasts, and the presence of monocytes and of T cells, respectively. Also cytokines were highly expressed, including CXCL8, IL-1β, CXCL2, MRP-14 and CXCL-10. The latter suggest T cell activation, a notion that could be confirmed by detecting a small, though conspicuous population of activated CD4+ cells in the peripheral blood T cells prior to surgery. Conclusion Our data support the concept that metallosis is the result of a local inflammatory response, which according to histomorphology and the composition of the cellular infiltrate classifies as an acute phase of a chronic inflammatory disease. The proinflammatory environment, particularly the generation of the osteoclast-inducing cytokines CXCL8 and IL1-β, promotes bone resorption. Loss of bone results in implant loosening, which then causes the major symptoms of metallosis, pain and reduced range of motion. [ABSTRACT FROM AUTHOR]

Bacterial infections of bones remain a serious complication of endoprosthetic surgery. These infections are difficult to treat, because many bacterial species form biofilms on implants, which are relatively resistant towards antibiotics. Bacterial biofilms elicit a progressive local inflammatory response, resulting in tissue damage and bone degradation. In the majority of patients, replacement of the prosthesis is required. To address the question of how the local inflammatory response is linked to bone degradation, tissue samples were taken during surgery and gene expression of the macrophage inflammatory proteins MIP1α (CCL3) and MIP2α (CXCL2) was assessed by quantitative RT-PCR. MIPs were expressed predominantly at osteolytic sites, in close correlation with CD14 which was used as marker for monocytes/macrophages. Colocalisation of MIPs with monocytic cells could be confirmed by histology. In vitro experiments revealed that, aside from monocytic cells, also osteoblasts were capable of MIP production when stimulated with bacteria;moreover, CCL3 induced the differentiation ofmonocytes to osteoclasts. In conclusion, the multifunctional chemokines CCL3 and CXCL2 are produced locally in response to bacterial infection of bones. In addition to their well described chemokine activity, these cytokines can induce generation of bone resorbing osteoclasts, thus providing a link between bacterial infection and osteolysis. [ABSTRACT FROM AUTHOR]

A patient in his late 50s who suffered from necrotising fasciitis is described in this case report. The patient first presented at the chest pain unit, where he reported of respiratory distress and showed systemic signs of an infection. Because of progressive skin lesions indicative of necrotising fasciitis on both the lower extremities, the patient was immediately rushed into surgery and was treated at the intensive care unit. Despite receiving immediate treatment, the patient died of this rapidly spreading infectious disease. Because of the fast advance of this disease, we would like to emphasise the importance of early recognition of symptoms. [ABSTRACT FROM AUTHOR]

Provides information on a study that assessed the prognostic significance of laryngeal electromyography in patients with vocal fold paralysis in a prospective design. Methodology; Results and discussion; Conclusions.

Background: Spinal infections represent a therapeutic challenge. The often protracted course of the disease is accompanied by pain, which can lead to a chronic pain experience even after the infectious disease has been treated successfully. The aim of this study was to investigate possible risk factors of pain chronification. Methods: In a prospective study, 14 patients with spinal infections were examined at admission (T1), at discharge from inpatient therapy (T2), and three to eight months postoperatively (T3) byquestionnaires on risk factors for pain chronification and by quantitative sensory testing (QST). Results: In-patient treatment lasted on average 45.3 days (±33.13). The patients complained of pain for 3.43 months (±2.77) prior to inpatient treatment. The visual analogue scale (VAS) for pain (0–10) and the Oswestry Disability Index detected significant improvement in the course of the study. However, patients also reported catastrophic thinking, as well as fear of movement and (re)-injury. Conclusion: In summary, our results demonstrate that patients with spinal infections did not suffer from pain chronification, but might benefit from an interdisciplinary therapeutic approach, which emphasizes promoting active pain-coping strategies, as well as addressing fear of movement and catastrophic thinking. [ABSTRACT FROM AUTHOR]

Background: Implant-associated infections are still a major complication in the field of orthopedics. Bacteria can form biofilms on implant surfaces, making them more difficult to detect and treat. Since standard antibiotic therapy is often impaired in biofilm infections, particular interest is directed towards finding treatment alternatives. Biofilm-formation is a well-organized process during which bacteria communicate via quorum-sensing molecules (QSM). The aim of this study was to inhibit bacterial communication by directing avian IgY against specific QSM. Methods: Chicken were immunized against the following QSM: (1) AtlE, a member of the autolysin family which mediates attachment to a surface in Staphylococcus epidermidis; (2) GroEL, the bacterial heat shock protein; (3) PIA (polysaccharide intercellular adhesion), which is essential for cell–cell adhesion in biofilms. Staphylococcus epidermidis biofilms were grown and inhibition of biofilm-formation by IgYs was evaluated. Additionally, human osteoblasts were cultivated and biocompatibility of IgYs was tested. Results: We were able to demonstrate that all IgYs reduced biofilm-formation, also without prior immunization. Therefore, the response was probably not specific with regard to the QSM. Osteoblasts were activated by all IgYs which was demonstrated by microscopy and an increased release of IL-8. Conclusions: In conclusion, avian IgY inhibits biofilm-formation, though the underlying mechanism is not yet clear. However, adverse effects on local tissue cells (osteoblasts) were also observed. [ABSTRACT FROM AUTHOR]