Bahram Biglari

Multicentre prospective observational study on professional wound care using honey (Medihoney

In recent years, the treatment of wounds with honey has received an increasing amount of attention from healthcare professionals in Germany and Austria. We conducted a prospective observational multicentre study using Medihoney™ dressings in 10 hospitals – nine in Germany and one in Austria. Wound‐associated parameters were monitored systematically at least three times in all patients. Data derived from the treatment of 121 wounds of various aetiologies over a period of 2 years were analysed. Almost half of the patients were younger than 18 years old, and 32% of the study population was oncology patients. Overall, wound size decreased significantly during the study period and many wounds healed after relatively short time periods. Similarly, perceived pain levels decreased significantly, and the wounds showed noticeably less slough/necrosis. In general, our findings show honey to be an effective and feasible treatment option for professional wound care. In addition, our study showed a relationship between pain and slough/necrosis at the time of recruitment and during wound healing. Future comparative trials are still needed to evaluate the extent to which the positive observations made in this and other studies can definitely be attributed to the effects of honey in wound care.

A retrospective study on flap complications after pressure ulcer surgery in spinal cord-injured patients

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.

Posttraumatic Inflammation as a Key to Neuroregeneration after Traumatic Spinal Cord Injury

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.

Quantification of TGF-ß1, PDGF and IGF-1 cytokine expression after fracture treatment vs. non-union therapy via masquelet.

INTRODUCTION Biochemical processes during bone regeneration can be analysed via quantification of peripheral serum cytokine levels. To date, serum levels of cytokines in patients treated with masquelet technique and patients with normal bone healing have not been compared. This comparison is supposed to deliver novel insights into the process of bone regeneration. Our aim was to validate this established method in the monitoring of bone regeneration after non-union treatment in masquelet technique. MATERIALS AND METHODS Between 04/2008 and 01/2014 three groups were recruited: G1 (10 patients) with long bone non-unions, treated successfully with masquelet therapy, G2 (6 patients) with unsuccessful masquelet therapy and G3 (10 patients) with long bone fractures and normal bone healing. Peripheral blood samples were collected over a period of six months following a standardised time pattern in combination with clinical and radiologic follow up. TGF-ß1, PDGF-AB and IGF-1 were measured using commercially available immunoassays. RESULTS TGF-ß1 levels in G1 and G2 demonstrated a parallel and lower overall concentration over time compared to G3. G3 showed a significant TGF-ß1 peak 2 weeks after surgery compared to G1 (p=0.0054). PDGF-AB concentrations were always lower in G2 than in G1 and G3. G3 peaked at week 2 with a significant higher value than in G2 (p=0.0177). IGF-1 showed lower overall serum concentrations in G2 than in G1 and G3. G1 had a peak level during the fourth week of follow-up. Compared to G2 this peak was significant (p=0.0015). CONCLUSIONS This study shows that successful bone regeneration via masquelet technique only partially imitates cytokine expression of physiological bone healing. High expressions of IGF-1 correspond to a successful masquelet therapy while TGF-ß seems to play a minor role. These results assume that objective analysis of an effective non-union therapy with cytokine expression analysis is possible even with a small number of patients.

Treatment of nonunions in fractures of the humeral shaft according to the Diamond Concept

METHODS Between 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. RESULTS A 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. DISCUSSION The 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.

Non-unions treated with bone morphogenic protein 7: introducing the quantitative measurement of human serum cytokine levels as promising tool in evaluation of adjunct non-union therapy

BackgroundIn this study we sought to determine if application of bone morphogenic protein 7 (BMP-7) promotes physiological bone healing of non-unions and to investigate if serum cytokine analysis may serve as a promising tool in the analysis of adjunct non-union therapy. Therefore we analyzed the influence of BMP-7 application on the serum cytokine expression patterns on patients with impaired bone healing compared to patients that showed proper bone healing.MethodsOur study involved analyzing blood samples from 208 patients with long bone fractures together with patients that subsequently developed non-unions. From this large pool, 15 patients with atrophic non-union were matched to 15 patients with atrophic non-union treated with local application of BMP-7 as well as normal bone healing. Changes in the cytokine expression patterns were monitored during the 1st, 2nd, 4th, 8th, 12th and 52nd week. The patients were followed both clinically and radiologically for the entire duration of the study. Serum cytokine expression levels of transforming growth factor beta (TGF-β), platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) were analyzed and compared.ResultsSerum expression of TGF-β were nearly parallel in all three groups, however serum concentrations were significantly higher in patients with proper bone healing and those treated with BMP-7 than in patients with non-unions (p < 0.05). bFGF serum concentrations increased initially in patients with proper bone healing and in those treated with BMP-7. Afterwards, values decreased; bFGF serum concentrations in the BMP-7 group were significantly higher than in the other groups (p < 0.05). PDGF serum concentration levels were nearly parallel in all groups, serum concentrations were significantly higher in patients with proper bone healing and those treated with BMP-7 than in patients with non-unions (p < 0.05).ConclusionTreatment with BMP-7 in patients with former non-unions led to similar cytokine expression patterns after treatment as those found in patients with proper bone healing. Our results suggest that treatment with BMP-7 promote healing of non-unions. Furthermore, quantitative measurement of serum cytokine expression is a promising tool for evaluating the effectiveness of additional non-union therapies such as adjunct application of growth factors.

Increase in soluble CD95L during subacute phases after human spinal cord injury: a potential therapeutic target

Study design:A pilot study measuring the levels of serum-soluble CD95 ligand (CD95L) in eight spinal cord-injured patients.Objectives:To determine the soluble concentration of CD95L in spinal cord injury (SCI) patients after trauma.Methods:We collected blood samples from eight patients with acute traumatic SCI. Soluble CD95L serum levels were determined using an enzyme-linked immunosorbent assay. American Spinal Injury Association (ASIA) was determined according to ASIA classification. The patients were monitored, and venous blood was drawn after arrival at the hospital on the 1st and 3rd day and during the 1st, 2nd, 4th, 8th and 12th weeks after trauma.Results:The average patient age was 48.1 years (18–86 years). Three patients were paraplegic (two incomplete, one complete), five were quadriplegic (one complete, four incomplete). The serum concentration of soluble CD95L (sCD95L) decreased during the 1st week (41 ng l−1) and increased after the 2nd week in all eight patients. It peaked during the 4th week (68.5 ng l−1) and reached a plateau during the 12th week (76.2 ng l−1). There are many possible explanations for not being able to detect a statistical significance, one of course being the small sample size.Conclusion:Promising results for anti-CD95L therapy have already been documented in lab studies with rodents. Anti-CD95L blocks the pro-apoptotic and proinflammatory activity of membrane-bound CD95L during the acute phase of SCI. We observed that sCD95L levels are elevated during the subacute and intermediate phases of SCI. It would be of great interest to study a larger group of patients to determine whether higher sCD95 levels are correlated with improved or impaired neurological outcome or with increasing levels of autoimmune components in peripheral blood.

A pilot study on temporal changes in IL-1β and TNF-α serum levels after spinal cord injury: the serum level of TNF-α in acute SCI patients as a possible marker for neurological remission

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; P<0.01). 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.

Elevated Serum Insulin-Like Growth Factor 1 Levels in Patients with Neurological Remission after Traumatic Spinal Cord Injury

After traumatic spinal cord injury, an acute phase triggered by trauma is followed by a subacute phase involving inflammatory processes. We previously demonstrated that peripheral serum cytokine expression changes depend on neurological outcome after spinal cord injury. In a subsequent intermediate phase, repair and remodeling takes place under the mediation of growth factors such as Insulin-like Growth Factor 1 (IGF-1). IGF-1 is a promising growth factor which is thought to act as a neuroprotective agent. Since previous findings were taken from animal studies, our aim was to investigate this hypothesis in humans based on peripheral blood serum. Forty-five patients after traumatic spinal cord injury were investigated over a period of three months after trauma. Blood samples were taken according to a fixed schema and IGF-1 levels were determined. Clinical data including AIS scores at admission to the hospital and at discharge were collected and compared with IGF-1 levels. In our study, we could observe distinct patterns in the expression of IGF-1 in peripheral blood serum after traumatic spinal cord injury regardless of the degree of plegia. All patients showed a marked increase of levels seven days after injury. IGF-1 serum levels were significantly different from initial measurements at four and nine hours and seven and 14 days after injury, as well as one, two and three months after injury. We did not detect a significant correlation between fracture and the IGF-1 serum level nor between the quantity of operations performed after trauma and the IGF-1 serum level. Patients with clinically documented neurological remission showed consistently higher IGF-1 levels than patients without neurological remission. This data could be the base for the establishment of animal models for further and much needed research in the field of spinal cord injury.

Exploratory study to suggest the possibility of MMP-8 and MMP-9 serum levels as early markers for remission after traumatic spinal cord injury

Study design:A prospective observational study reporting the correlation between matrix metalloprotein serum levels and remission after traumatic spinal cord injury (SCI).Objectives:To investigate serum cytokine levels as predictive markers.Setting:Germany, Rhineland-Palatinate (Rheinland-Pfalz).Methods:Between 2010 and 2015, data sets from 115 patients (33 female, 82 male) after traumatic SCI were recorded at the BG Trauma Centre Ludwigshafen. We examined the serum levels of Matix metallopraoteinases (MMPs) MMP-2, MMP-8, MMP-9, MMP-10 and MMP-12 over a 12-week period, that is, at admission and 4, 9, 12 h, 1 and 3 days and 1, 2, 4, 8 and 12 weeks after trauma. Following the same match-pair procedure as in our previous studies, we selected 10 patients with SCI and neurological remission (Group 1) and 10 patients with an initial American Spinal Injury Association (ASIA) A grade and no neurological remission (Group 0). Ten patients with an isolated vertebral fracture without neurological deficits served as a control group (Group C). Our analysis was performed using a Luminex Performance Human High Sensitivity Cytokine Panel. Multivariate logistic regression models were used to examine the predictive value of MMPs with respect to neurological remission vs no neurological remission.Results:MMP-8 and MMP-9 provided significantly different values. The favoured predictive model allows to differentiate between neurological remission and no neurological remission in 97% of cases.Conclusions:The results indicate that further studies with an enlarged collective are warranted in order to investigate current monitoring, prognostic and tracking techniques as well as scoring systems.