Injury to the central nervous system initiates an uncontrolled inflammatory response that results in both tissue repair and destruction. Here, we showed that, in rodents and humans, injury to the spinal cord triggered surface expression of CD95 ligand (CD95L, FasL) on peripheral blood myeloid cells. CD95L stimulation of CD95 on these cells activated phosphoinositide 3-kinase (PI3K) and metalloproteinase-9 (MMP-9) via recruitment and activation of Syk kinase, ultimately leading to increased migration. Exclusive CD95L deletion in myeloid cells greatly decreased the number of neutrophils and macrophages infiltrating the injured spinal cord or the inflamed peritoneum after thioglycollate injection. Importantly, deletion of myeloid CD95L, but not of CD95 on neural cells, led to functional recovery of spinal injured animals. Our results indicate that CD95L acts on peripheral myeloid cells to induce tissue damage. Thus, neutralization of CD95L should be considered as a means to create a controlled beneficial inflammatory response.

Study design: A retrospective study reporting specific complications of certain skin flaps for treating pressure ulcers. Objectives: To describe the rate and type of complications after pressure ulcer surgery in patients with spinal cord injury. Setting: Germany, Rheinland Pfalz. Methods: We collected data from 352 patients treated with 421 skin flaps to determine the rate and type of complications of each skin flap used. Results: In this study, we analyzed the results of 421 skin flaps in 352 patients with a total of 657 pressure ulcers from January 2006 to December 2010. Our patients had ischial, pelvic, sacral, trochanteric and lower extremity ulcers. Ischial ulcers were most common, followed by sacral and trochanteric ulcers. There were 87 complications in 421 flaps, which was an overall rate of 21%. Suture line dehiscence was the most common complication with 27 cases (31%), followed by 22 cases of infection (25.2%), 17 cases of hematoma (19.5%), 12 cases of partial necrosis (13.7%) and 9 cases of total flap necrosis (10.3%). Conclusion: Pressure ulcers in spinal cord-injured patients are very common and difficult and expensive to treat. The high rate of complications and the associated costs suggest the importance of evaluating the efficacy of treatment options. Conservative procedures have been standardized, but there still has been limited success in establishing guidelines on how to manage complications arising from flap surgery. Our extensive documentation of flap plastics will be useful managing complications after the surgical treatment of pressure ulcers in spinal cord-injured patients.

Study design: Serum levels of interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α) were measured over a 12-week period in 23 patients with spinal cord injury (SCI) with and without neurological improvement. Objectives: To determine the course of IL-1β and TNF-α in patients with SCI and observe a possible relationship between improvements in neurological functioning and cytokine levels. Setting: All patients were treated at the BG Trauma Centre, Ludwigshafen, Germany. All lab work was done at the University Hospital, Heidelberg. Methods: Spinal cord injury was classified according to the American Spinal Injury Association (ASIA) impairment scale (AIS) in 23 patients. TNF-α and IL-1β levels were measured upon arrival at the hospital, after 4 h, 9 h and 12 h, on days 1 and 3 and at the end of weeks 1, 2, 4, 8 and 12. Results: Temporal changes in TNF-α and IL-1β in SCI patients were seen. Patients with AIS improvement (Group 1) had significantly lower TNF-α levels at 9 h compared with patients without AIS improvement (Group 2; Po0.01). The course of IL-1β fluctuated greatly between 4 h and week 1 in the groups; however, between 2 and 12 weeks post trauma, there was an overall decline in both groups. Conclusion: Measuring serum levels of TNF-α and IL-1β over time could be useful in tracking the course of SCI. Our data show differences in measured cytokines over a 12-week period for SCI patients with and without neurological improvement.

MethodsBetween 2005 and 2012, 50 patients (23 female, 27 male) with nonunion of the humeral shaft were included in this retrospective study. The mean age was 51.3 years (14 to 88). The patients had a mean of 1.5 prior operations (SD 1.2;1 to 8).All patients were assessed according to a specific risk score in order to devise an optimal and individual therapy plan consistent with the Diamond Concept. In 32 cases (64%), a change in the osteosynthesis to an angular stable locking compression plate was performed. According to the individual risk an additional bone graft and/or bone morphogenetic protein-7 (BMP-7) were applied. ResultsA successful consolidation of the nonunion was observed in 37 cases (80.4%) with a median healing time of six months (IQR 6). Younger patients showed significantly better consolidation. Four patients were lost to follow-up. Revision was necessary in a total of eight (16%) cases. In the initial treatment, intramedullary nailing was most common. DiscussionThe use of locking compression plates in combination with autologous cancellous bone graft has been shown to be a safe and effective treatment. In more complex cases, the use of the Masquelet technique and BMP-7 may be indicated at the first revision operation. Take home message: Our results suggest the Diamond Concept is a successful treatment strategy for nonunions of the humeral shaft. Cite this article: BoneJoint J 2016;98-B:81-7.

Study design: Prospective, observational study of 20 spinal cord-injured (SCI) patients with chronic pressure ulcers (PUs) using Medihoney. Objectives: To determine the effects of Medihoney by bacterial growth, wound size and stage of healing in PUs. Methods: We treated 20 SCI adult patients with chronic PUs using Medihoney. In all, 7 patients (35%) were female, and 13 (65%) were male. The average patient age was 48.7 years (30-79). In all, 6 patients (30%) were tetraplegic and 14 (70%) were paraplegic. Also, 5 patients (25%) had grade IV ulcers and 15 patients (75%) had grade III ulcers according to the National Pressure Ulcer Advisory Panel. Results: After 1 week of treatment with Medihoney, all swabs were void of bacterial growth. Overall 18 patients (90%) showed complete wound healing after a period of 4 weeks, and the resulting scars were soft and elastic. No negative effects were noted from the treatment using Medihoney. No blood sugar level derailment was documented. Conclusion: The medical-honey approach to wound care must be part of a comprehensive conservative surgical wound-care concept. Our study indicates the highly valuable efficacy of honey in wound management and infection control as measured by bacterial growth, wound size and healing stage.

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Pro- and anti-inflammatory cytokines might have a large impact on the secondary phase and on the neurological outcome of patients with acute spinal cord injury (SCI). We measured the serum levels of different cytokines (Interferon-γ, Tumor Necrosis Factor-α, Interleukin-1β, IL-6, IL-8, IL-10, and Vascular Endothelial Growth Factor) over a 12-week period in 40 acute traumatic SCI patients: at admission on average one hour after initial trauma; at four, nine, 12, and 24 h; Three, and seven days after admission; and two, four, eight, and twelve weeks after admission. This was done using a Luminex Performance Human High Sensitivity Cytokine Panel. SCI was classified using the American Spinal Injury Association (ASIA) Impairment Scale (AIS) at time of admission and after 12 weeks. TNFα, IL-1β, IL-6, IL-8, and IL-10 concentrations were significantly higher in patients without neurological remission and in patients with an initial AIS A (p < 0.05). This study shows significant differences in cytokine concentrations shown in traumatic SCI patients with different neurological impairments and within a 12-week period. IL-8 and IL-10 are potential peripheral markers for neurological remission and rehabilitation after traumatic SCI. Furthermore our cytokine expression pattern of the acute, subacute, and intermediate phase of SCI establishes a possible basis for future studies to develop standardized monitoring, prognostic, and tracking techniques.

Our study was able to show that the cytokine expression pattern in physiological bone healing is similar to that in successful non-union treatment with intramedullary reaming. Our results show that the effect of non-union therapy could be observed objectively by measuring cytokine expression patterns in peripheral blood even in a small group of patients.