Benzoyl peroxide treatment decreases Cutibacterium acnes in shoulder surgery, from skin incision until wound closure.

INTRODUCTION: Most surgical site infections after shoulder surgery are caused by Cutibacterium acnes. Topically applied benzoyl peroxide (BPO) has for years been used to decrease the skin load of C acnes in treatment of acne vulgaris. The purpose of this study was to examine this effect on bacterial colonization in patients subjected to elective shoulder surgery at different stages of the procedure. METHODS: A total of 100 patients scheduled for primary elective open shoulder surgery were randomized to prepare either with BPO or according to local guidelines-with soap (control group). Four skin swabs were taken in a standardized manner at different times, before and after surgical skin preparation, 1 in dermis, and finally after the skin was sutured. Before skin incision, 5 punch biopsies (3 mm in diameter and maximum 4 mm deep) were retrieved spaced 2 cm apart in the planned skin incision. On culturing, quantification of C acnes was made by serial dilutions. RESULTS: Men had a 5-fold higher amount of C acnes on untreated skin. Treatment with BPO considerably lowered this count (P = .0001) both before and after skin disinfection compared to the control group. This positive effect of BPO persisted until skin closure, the point at which some recolonization of C acnes had occurred, but to a higher degree in the control group (P = .040). CONCLUSION: Preoperative BPO treatment of the shoulder may be an effective method to decrease bacterial skin load of C acnes from skin incision until wound closure.

The pencil eraser swab technique to quantify Cutibacterium acnes on shoulder skin.

Introduction: Cutibacterium acnes is the most common cause of postoperative infections in orthopaedic shoulder surgery and is hard to eradicate with current measures. Newer strategies focus on reducing bacterial load on the skin before surgery. Several previous studies have used a large number of both described and undescribed sampling techniques. The purpose of this study was to compare three previously described swab techniques to obtain bacterial cultures: Levine's (L) technique, the Z technique and the pencil eraser swab (PES) technique. Methods: Three consecutive skin swabs were collected from the right shoulder, on 15 healthy male volunteers, using Levine's technique, Z technique and PES technique from each participant. To determine the number of living bacteria, serial dilutions were made, and after culturing for 5 d, viable count (VC) was expressed as CFU/mL (with CFU representing colony-forming unit). Results: The PES technique yielded significantly higher VC than the two others. PES: median 3700 CFU/mL, L: 200 CFU/mL and Z: 220 CFU/mL ( p = 0.003 ). There was no significant difference between the methods regarding the number of positive cultures. PES: 14/15, L: 11/15 and Z: 12/15. Conclusions: There is a need to harmonise sampling techniques of C. acnes in order to compare the efficacy of different measures to reduce the bacterial load on the skin before and during surgery. Of the three tested methods, the PES technique is simple and produces the highest bacterial counts.

Topical benzoyl peroxide application on the shoulder reduces Propionibacterium acnes: a randomized study.

BACKGROUND: Propionibacterium acnes is a common cause of infection following shoulder surgery. Studies have shown that standard surgical preparation does not eradicate P acnes. The purpose of this study was to examine whether topical application of benzoyl peroxide (BPO) gel could decrease the presence of P acnes compared with today's standard treatment with chlorhexidine soap (CHS). We also investigated and compared the recolonization of the skin after surgical preparation and draping between the BPO- and CHS-treated groups. METHODS: In this single-blinded nonsurgical study, 40 volunteers-24 men and 16 women-were randomized to preoperative topical treatment at home with either 5% BPO or 4% CHS on the left shoulder at the area of a deltopectoral approach. Four skin swabs from the area were taken in a standardized manner at different times: before and after topical treatment, after surgical skin preparation and sterile draping, and 120 minutes after draping. RESULTS: Topical treatment with BPO significantly reduced the presence of P acnes measured as the number of colony-forming units on the skin after surgical preparation. P acnes was found in 1 of 20 subjects in the BPO group and 7 of 20 in the CHS group (P = .044). The results remained after 2 hours (P = .048). CONCLUSION: Topical preparation with BPO before shoulder surgery may be effective in reducing P acnes on the skin and preventing recolonization.

The Scandinavian Sarcoma Group Central Register: 6,000 patients after 25 years of monitoring of referral and treatment of extremity and trunk wall soft-tissue sarcoma.

Purpose - We wanted to examine the potential of the Scandinavian Sarcoma Group (SSG) Central Register, and evaluate referral and treatment practice for soft-tissue sarcomas in the extremities and trunk wall (STS) in the Nordic countries. Background - Based on incidence rates from the literature, 8,150 (7,000-9,300) cases of STS of the extremity and trunk wall should have been diagnosed in Norway, Finland, Iceland, and Sweden from 1987 through 2011. The SSG Register has 6,027 cases registered from this period, with 5,837 having complete registration of key variables. 10 centers have been reporting to the Register. The 5 centers that consistently report treat approximately 90% of the cases in their respective regions. The remaining centers have reported all the patients who were treated during certain time periods, but not for the entire 25-year period. Results - 59% of patients were referred to a sarcoma center untouched, i.e. before any attempt at open biopsy. There was an improvement from 52% during the first 5 years to 70% during the last 5 years. 50% had wide or better margins at surgery. Wide margins are now achieved less often than 20 years ago, in parallel with an increase in the use of radiotherapy. For the centers that consistently report, 97% of surviving patients are followed for more than 4 years. Metastasis-free survival (MFS) increased from 67% to 73% during the 25-year period. Interpretation - The Register is considered to be representative of extremity and trunk wall sarcoma disease in the population of Scandinavia, treated at the reporting centers. There were no clinically significant differences in treatment results at these centers.

Prognostic role of en-bloc resection and late onset of bone metastasis in patients with bone-seeking carcinomas of the kidney, breast, lung, and prostate: SSG study on 672 operated skeletal metastases.

BACKGROUND AND OBJECTIVES: In metastatic disease, decisions regarding potential surgery require reliable data about the patient's survival. In this study, we evaluated different prognostic factors and their impact in four common primary tumors causing bone metastases. METHODS: Data were acquired from the Scandinavian Sarcoma Group (SSG) metastasis registry. The patients underwent surgery between July 1999 and July 2009. This study included breast, prostate, lung, and kidney cancer cases, with a total of 672 operated non-spinal metastases. Differences in prognostic factors were evaluated using the Kaplan-Meier method with long-rank test. Cox regression multivariate analysis was performed to identify statistically independent prognostic factors. RESULTS: Significant factors affecting survival were the presence of organ metastases, overall heath status, and disease load. In kidney cancer, en bloc resection of solitary metastases was associated with a significant fourfold longer survival compared to intralesional surgery. Preoperative radiotherapy was associated with higher complication and reoperation rates. CONCLUSIONS: This data summary is important tool for clinicians to evaluate survival and choose treatment options for patients suffering from metastatic bone disease.

Insight opinion to surgically treated metastatic bone disease: Scandinavian Sarcoma Group Skeletal Metastasis Registry report of 1195 operated skeletal metastasis.

The number of cancer patients living with metastatic disease is growing. The increased survival has led to an increase in the number of cancer-induced complications, such as pathologic fractures due to bone metastases. Surgery is most commonly needed for mechanical complications, such as fractures and intractable pain. We determined survival, disease free interval and complications in surgically treated bone metastasis. Data were collected from the Scandinavian Skeletal Metastasis Registry for patients with extremity skeletal metastases surgically treated at eight major Scandinavian referral centres between 1999 and 2009 covering a total of 1195 skeletal metastases in 1107 patients. Primary breast, prostate, renal, lung, and myeloma tumors make up 78% of the tumors. Number of complications is tolerable and is affected by methods of surgery as well as preoperative radiation therapy. Overall 1-year patient survival was 36%; however, mean survival was influenced by the primary tumor type and the presence of additional visceral metastases. Patients with impending fracture had more systemic complications than those with complete fracture. Although surgery is usually only a palliative treatment, patients can survive for years after surgery. We developed a simple, useful and reliable scoring system to predict survival among these patients. This scoring system gives good aid in predicting the prognosis when selecting the surgical method. While it is important to avoid unnecessary operations, operating when necessary can provide benefit.

Complications and survival after surgical treatment of 214 metastatic lesions of the humerus.

BACKGROUND: The humerus is the second most common long-bone site of metastatic bone disease. We report complications, risk factors for failure, and survival of a large series of patients operated on for skeletal metastases of the humerus. MATERIALS AND METHODS: This study was based on 208 patients treated surgically for 214 metastatic lesions of the humerus. Reconstructions were achieved by intramedullary nails in 148, endoprostheses in 35, plate fixation in 21, and by other methods in 10. RESULTS: The median age at surgery was 67 years (range, 29-87 years). Breast cancer was the primary tumor in 31%. The overall failure rate of the surgical reconstructions was 9%. The reoperation rate was 7% in the proximal humerus, 8% in the diaphysis, and 33% in the distal part of the bone. Among 36 operations involving an endoprosthesis, 2 were failures (6%) compared with 18 of 178 osteosynthetic devices (10%). In the osteosynthesis group, intramedullary nails failed in 7% and plate fixation failed in 22%. Multivariate Cox regression analysis showed that prostate cancer was associated with an increased risk of failure after surgery (hazard ratio, 7; P < 0.033). The cumulative survival after surgery was 40% (95% confidence interval [CI] 34-47) at 1 year, 21% (95% CI, 15-26) at 2 years, and 16% (95% CI, 12-19) at 3 years. CONCLUSIONS: Our method of choice is the cemented hemiprosthesis for pathologic proximal humeral fractures and interlocked intramedullary nail for lesions in the diaphysis. Pathologic fractures in the distal humerus are uncommon and associated with a very high reoperation rate.

Acidic preparations of lysed platelets upregulate proliferative pathways in osteoblast-like cells as demonstrated by genome-wide microarray analysis.

Platelets contain numerous growth factors essential for wound and fracture healing. We investigated the gene expression in human osteoblast-like cells stimulated with lysed platelets prepared in acidic, neutral, or alkaline buffers. Lysed platelets prepared in buffers at pH 5.4, 7.4, and 7.9, were added after neutralization to hFOB 1.19 cells. Genome-wide microarray analysis was performed using the Affymetrix GeneChip 7G Scanner. Biometric, cluster, and pathway analyses were performed with GeneSpring GX. Biometric analyses demonstrated that 53 genes were differentially regulated (p ≤ 0.005, ≥2-fold increase). Pathway analysis revealed 10 significant pathways of which eight are common ones regulating bone formation and cancer growth. Eleven genes were selected for quantitative real-time polymerase chain reaction (PCR) based on the microarray analysis of the lysed platelets prepared in the pH 5.4 experiments. In conclusion, acidic preparations of lysed platelet concentrates release factors essential for cell proliferation and particularly cell metabolism under hypoxic conditions. The genetic response from these factors was dominated by genes associated with the same pathways observed in bone formation and cancer growth. Activation of TGF-ß in the acidic preparation could be a stimulatory key factor of cell proliferation. These results support the hypothesis that acidification of platelets modifies the stimulatory response of mesenchymal cells in vitro, which is analogous with the observed milieu of a low pH present in wound and fracture sites, as well as in growing tumors.

Preparation for becoming members of health care teams: findings from a 5-year evaluation of a student interprofessional training ward.

SETTING: An orthopaedic interprofessional training ward manned by students at a University Hospital. OBJECTIVE: To assess to what extent students from different undergraduate programmes evaluated the effects of a 2-week rotation at the ward on their professional roles and the value of teamwork within health care. METHOD: A questionnaire was filled in by 841 students by the end of a 2-week rotation at the ward over 5 years. Questions concerned students' estimate of how the rotation had strengthened their insight into their own future professional role, into other students' professional roles and into the value of teamwork within health care. Differences between the different student categories and possible associations between the different estimates were statistically analysed. RESULTS: Students from all programmes reported that the rotation at the student ward had dramatically strengthened their insight about their own future professional role as well as the roles of the other professions and the value of teamwork within health care. CONCLUSION: Health care is a complicated system based on cooperation and professionalism. We suggest that interprofessional training of students from all professions within health care should be a part of their education as a worthwhile preparation for their future professional work and to ensure high-quality health care.

The content of bone morphogenetic proteins in platelets varies greatly between different platelet donors.

Platelet derivates and platelet rich plasma have been used to stimulate bone formation and wound healing because of the rich content of potent growth factors. However, not all reports have been conclusive since some have not been able to demonstrate a positive effect. We investigated the interindividual variation of bone morphogenetic proteins (BMPs) in platelets from healthy donors, and the pH-dependent effect on the release of BMPs in preparations of lysed platelets in buffer (LPB). Platelet concentrates from 31 healthy donors were prepared in pH 4.3 and pH 7.4 buffers and investigated with respect to BMP-2, -4, -6, and -7. BMP-2 and BMP-4 were significantly more common in acidic LPBs in comparison with neutral preparations. We also observed a considerable variation among platelet donors with respect to the release of BMPs at pH 4.3 and 7.4. In conclusion, a considerable variation was found among platelet donors, which may be of importance considering the ambiguous results previously reported on osteoblast proliferation and differentiation.

Acidic preparations of platelet concentrates release bone morphogenetic protein-2.

BACKGROUND AND PURPOSE: Growth factors released from platelets have potent effects on fracture and wound healing. The acidic tide of wound healing, i.e. the pH within wounds and fractures, changes from acidic pH to neutral and alkaline pH as the healing process progresses. We investigated the influence of pH on lysed platelet concentrates regarding the release of growth factors. MATERIAL AND METHODS: Platelet concentrates free of leukocyte components were lysed and incubated in buffers with pH between 4.3 and 8.6. Bone morphogenetic protein-2 (BMP-2), platelet-derived growth factor (PDGF), transforming growth factor-beta(TGF-beta), and vascular endothelial growth factor (VEGF) were measured by quantitative enzyme-linked immunosorbent assays. RESULTS: PDGF, TGF-beta, and VEGF were present in all platelet preparations but the levels varied in a pH-dependent fashion. BMP-2 was only detected in the most acidic preparation (pH 4.3), which is interesting since BMP-2 has been reported to be an endogenous mediator of fracture repair and to be responsible for the initiation of fracture healing. INTERPRETATION: Our findings indicate that platelets release substantial amounts of BMP-2 only under conditions of low pH, the milieu associated with the critical initial stage of fracture healing.

Variation of pH in lysed platelet concentrates influence proliferation and alkaline phosphatase activity in human osteoblast-like cells.

Activated platelets release a multifaceted blend of growth factors that has stimulatory effects on mesenchymal cells, both in vitro and in vivo, which imply beneficial effects on wound repair and tissue regeneration. Previous studies on fibroblast cultures have revealed that more potent growth factors, with respect to cell proliferation, are released in acidic preparations of lysed platelet concentrates in comparison with neutral and alkaline preparations. The current study was intended to investigate the influence of pH on lysed platelet concentrates with respect to release of growth factors, cell proliferation and alkaline phosphatase (ALP) activity in human osteoblast-like cells (hFOB 1.19). Cell proliferation was assessed with the MTT kit, ALP activity by conventional enzymatic reaction kinetics and growth factors platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta) by enzyme-linked immunosorbent assays. Osteoblast-like cells were stimulated with lysed platelet concentrates preincubated at pH 4.4, 5.4, 7.4, and 7.6. A 3-13-fold increase of cell proliferation was found in comparison with controls and the most evident increase was observed with platelets activated at pH 5.4. The highest ALP activity was observed in preparations at pH 7.6. Platelets incubated in an acidic environment (pH 5.4) induced a higher proliferation compared with preincubation at neutral or alkaline pH and the level of PDGF was also found to be higher in acidic preincubations. The level of TGF-beta was, in contrast, lowest at pH 4.4. We suggest, based on these experimental findings, that acidic milieu influence platelets to release growth factors more potent to stimulate osteoblast proliferation than neutral and alkaline platelet preparations. Lysed platelet concentrates prepared at an alkaline pH might release additional components with stimulating effects resulting in other features than cell proliferation. This is the first report, to our knowledge, about a pH dependent stimulatory effect of lysed platelet concentrates on human osteoblast-like cell proliferation. Lysed platelet concentrates, preincubated in acidic or alkaline buffers, may benefit fracture healing, implant fixation and might also be advantageous in the treatment of wounds with platelet constituents; however, this has to be investigated in extended experimental and clinical settings.

Fusion of the EWSR1 and ATF1 genes without expression of the MITF-M transcript in angiomatoid fibrous histiocytoma.

Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor that usually occurs in children and young adults. Only two cases of AFH with genetic rearrangements have been reported previously; both of these had a FUS-ATF1 fusion gene. We have studied an AFH from a 9-year-old boy whose tumor displayed a t(12;22)(q13;q12) as the sole cytogenetic aberration. FISH,RT-PCR, and sequence analyses revealed an EWSR1-ATF1 fusion gene that has previously been reported in clear cell sarcoma (CCS), a soft tissue sarcoma that is morphologically and clinically distinct from AFH. This study thus has demonstrated that the EWSR1-ATF1 chimera represents a fusion gene that can be associated with different tumor types. Simultaneous expression of the EWSR1-ATF1 and MITF-M transcripts in CCS has led to the proposal that the MITF-M promoter is transactivated by EWSR1-ATF1. The AFH, however, did not express the MITF-M transcript, supporting the theory that MITF-M expression in CCS is a reflection of its cellular origin, rather than a consequence of the presence of an EWSR1-ATF1 fusion protein. Activation of the EWSR1-ATF1 oncogene is probably an early step in the transformation process, but the overall gene expression patterns are likely to vary considerably between AFH and CCS, in keeping with their clinicopathologic differences.

Time- and pH-dependent release of PDGF and TGF-beta from platelets in vitro.

We studied the spontaneous and thrombin-induced activation of platelets and their release of platelet derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta) at different pH values. Platelet activation was assayed with antibodies against P-selectin and performed in serum-free media. The release of PDGF and TGF-beta was determined by ELISA after 15 min and 12h. There was no activation at pH 5.0, while a time-dependent release of growth factors occurred at neutral and alkaline pH. The results suggest that release o f growth factors is not only dependent on platelet activation but also on incubation time and pH. Although the used serum-free experimental situation is different from normal conditions for platelets in vivo, the findings of a late release of growth factors may, nevertheless, be relevant to wound healing.

Fibroblast proliferation due to exposure to a platelet concentrate in vitro is pH dependent.

The influence of platelet-rich plasma lysates on fibroblast proliferation was studied in culture. Cells were exposed to platelet lysates that had been preincubated at different pHs (5.0, 7.1, and 7.6). Proliferation was evaluated with the MTT assay and incorporation of [3H]thymidine into macromolecules, while type I collagen production was assayed by Western blotting. Enzyme-linked immunosorbent assays were used to determine platelet-derived growth factor and transforming growth factor-beta concentrations. Platelets preincubated in an acidic environment (pH 5.0) induced the highest degree of fibroblast proliferation, and the concentration of platelet-derived growth factor in the different treated lysates was the highest at that particular pH. The concentration of transforming growth factor-beta, however, was lower after incubation at pH 5.0 than at either pH 7.1 or 7.6. These findings may be relevant to normal wound healing in vivo and useful in the treatment of wounds and delayed healing processes.