Increased Age, Cardiovascular Comorbidities, COPD, and Diabetes mellitus Determine Excess Mortality in Trauma Patients with SSI or Chronic Wounds. / Erhöhtes Alter, kardiovaskuläre Nebenerkrankungen, COPD und Diabetes mellitus bedingen eine Übersterblichkeit in der septischen Unfallchirurgie.

BACKGROUND: The constant aging of the German population leads, among other things, to an increase in the average age of hospitalised patients. In association with the reduced physiological reserve and the endogenous defence mechanism, this results in an increased susceptibility to infections and complications. Compared with that in trauma patients, the age distribution in patients with surgical site infections (SSI) has been poorly studied. Studies on the impact of age, diverse underlying diseases and influence of alcohol and nicotine consumption on the mortality risk in patients with SSI are limited. METHODS: In 2014/15 (Exam 1), 345 patients with SSI were included in this study. The 3-year follow-up examination was performed in 2017/18 (Exam 2). The questionnaires (Exams 1 and 2) assessed demographic parameters, comorbidities, medication use, alcohol and nicotine consumption, and different risk factors related to morbidity. The mortality risk in patients with SSI was calculated as a function of various risk factors (age, comorbidities, medication intake, and noxious agents). Furthermore, the development of the patients' age in the trauma department, especially of those with SSI, were evaluated between 2010 and 2019. RESULTS: In 2014/15 (Exam 1), 345 patients were included in the study. Of these, 274 (79.4%) were contacted by telephone in 2017/18. Thirty-six (10.4%) declined to be questioned again. Twenty (8.4%) of the 238 remaining participants had already died, resulting in 218 patients (63.2%) re-participating. From 2010 (n = 492) to 2019 (n = 885), the number of patients with SSI increased by 79.9%, especially those aged < 65 years. After the age of 60 years, the mortality risk increased rapidly (60 years: 0.0377 vs 70 years: 0.1395); the mortality risk of a 60-year-old patient with SSI was equal to that of an 80-year-old in the general population. Nicotine (p = 0.93) and alcohol consumption (p = 0.344) had no significant effect on mortality, whereas history of cardiac disease (p = 0.01), chronic obstructive pulmonary disease (COPD) (p = 0.01), diabetes mellitus (p = 0.05) and peripheral artery disease (p = 0.01) were associated with a significant increase in the mortality risk. CONCLUSION: Age, pre-existing cardiac conditions, as well as COPD, diabetes mellitus and peripheral artery disease are associated with a significantly increased mortality risk in patients with SSI. Thus, an exponential increase in mortality risk was found between the ages of 50 and 60 years, with the mortality risk of a 60-year-old patient with SSI being equivalent to that of an 80-year-old in the general population.

Risk of malnutrition in orthopedic trauma patients with surgical site infections is associated with increased morbidity and mortality - a 3-year follow-up study.

BACKGROUND: Malnutrition is a worldwide problem which can result in prolonged hospitalization from complications such as poor wound healing and increased morbidity. There is increasing evidence of the effect of risk of malnutrition (ROM) on outcomes in orthopedic surgical patients. However, there is little data on the effect of nutritional status on clinical outcomes in orthopedic trauma patients with surgical site infections (SSI). Therefore, our aim was to investigate how malnutrition risk affects clinical outcomes in a prospective cohort of orthopedic trauma patients with SSI. METHODS: The study included 345 patients who underwent surgery due to SSI at a level 1 trauma center. All patients were evaluated on their nutritional status as assessed by the Nutritional Risk Screening in 2014/15 and 2017/18. 238 (69.0%) datasets were available for the follow-up analysis. Twenty patients (8.4%) had died, resulting in 218 patients. Outcomes investigated included comorbidities, medication intake, destination of discharge, degree of mobility, support for procuring food, mortality risk and quality of life. RESULTS: 32.8% were at risk of malnutrition (ROM) at EXAM1. Female patients had a higher ROM than males (p < 0.05). Patients with ROM had more comorbidities (p < 0.001), an increased need for medication intake (p < 0.001), a decreased level of mobility (p < 0.001) and increased need of support in procuring food (p < 0.001). The destination of discharge was independent of the nutritional status (p = 0.641). Twenty (8.4%) of the available 238 patients had died during follow-up time period, resulting in a 6.2-times higher risk of mortality in patients with ROM. EQ-5D revealed that mobility, self-supply and usual activities of daily living were increased in well-nourished patients (p < 0.001). CONCLUSION: ROM in orthopedic trauma patients with SSI is associated with an increased number of comorbidities and need for medication intake, a decrease in mobility and a higher dependency for food acquisition. Patients at ROM exhibited a 6.2-times higher mortality rate than well-nourished patients. EQ-5D evaluation showed better mobility, self-supply, and activity of daily living in well-nourished patients. We therefore strongly recommend supplementing patients with ROM with a specific diet during and after discharge from the hospital in order to reduce postoperative complications and long-term mortality.

[Black knee-ochronotic alterations in alkaptonuria]. / Das schwarze Knie ­ ochronotische Veränderungen im Rahmen einer Alkaptonurie.

This article presents the case of a 53-year-old male patient born in Sri Lanka, who presented to the outpatient unit with the suspicion of empyema of the knee joint. Within the framework of knee arthroscopy, the diagnosis of ochronosis was made and later confirmed by histopathological biopsy. The alkaptonuria is caused by a homogentisate 1,2-dioxygenase deficiency and leads to an accumulation of homogentisic acid, a degradation product of tyrosine. This leads to the characteristic appearance of ochronosis with bluish-black deposits in the tissue (e.g. in connective tissue, sclera and ear cartilage) and a black coloration of the urine.

Smoking Dependent Alterations in Bone Formation and Inflammation Represent Major Risk Factors for Complications Following Total Joint Arthroplasty.

Numerous studies have described a correlation between smoking and reduced bone mass. This not only increases fracture risk but also impedes reconstruction/fixation of bone. An increased frequency of complications following surgery is common. Here, we investigate the effect of smoking on the clinical outcome following total joint arthroplasty (TJA). 817 patients receiving primary or revision (including clinical transfers) TJA at our level-one trauma center have been randomly interviewed twice (pre- and six months post-surgery). We found that 159 patients developed complications (infections, disturbed healing, revisions, thrombosis, and/or death). Considering nutritional status, alcohol and cigarette consumption as possible risk factors, OR was highest for smoking. Notably, mean age was significantly lower in smokers (59.2 ± 1.0a) than non-smokers (64.6 ± 0.8; p < 0.001). However, the number of comorbidities was comparable between both groups. Compared to non-smokers (17.8 ± 1.9%), the complication rate increases with increasing cigarette consumption (1⁻20 pack-years (PY): 19.2 ± 2.4% and >20 PY: 30.4 ± 3.6%; p = 0.002). Consequently, mean hospital stay was longer in heavy smokers (18.4 ± 1.0 day) than non-smokers (15.3 ± 0.5 day; p = 0.009) or moderate smokers (15.9 ± 0.6 day). In line with delayed healing, bone formation markers (BAP and CICP) were significantly lower in smokers than non-smokers 2 days following TJA. Although, smoking increased serum levels of MCP-1, OPG, sRANKL, and Osteopontin as well as bone resorption markers (TRAP5b and CTX-I) were unaffected. In line with an increased infection rate, smoking reduced 25OH vitamin D3 (immune-modulatory), IL-1ß, IL-6, TNF-α, and IFN-γ serum levels. Our data clearly show that smoking not only affects bone formation after TJA but also suppresses the inflammatory response in these patients. Thus, it is feasible that therapies favoring bone formation and immune responses help improve the clinical outcome in smokers following TJA.

Quality of life and clinical-radiological long-term results after implant-associated infections in patients with ankle fracture: a retrospective matched-pair study.

BACKGROUND: Ankle fractures are frequently occurring injuries. Despite the relatively simple operative technique, patients often suffer from postoperative complications. Little is known about postoperative treatment of implant-associated infections of the ankle. Therefore, this study shows and evaluates a treatment algorithm in long- and short-term outcomes compared to infection-free patients. METHODS: Data from patients of over 20 years of a level 1 trauma center and university hospital was retrospectively analyzed including age, gender, comorbidities, smoking status, fracture classification, number of revisions, length of in-patient stay due to fracture and infection, and results of microbiological specimen with the length of antibiotic treatment. Moreover, present long-term outcome was evaluated by the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score, the Ankle Osteoarthritis Score, and the Short Form 36 score and compared to a matched-pair infection-free patient cohort. RESULTS: Forty-four patients could be retrospectively evaluated (51% male, 49% women, mean age 46 ± 17 years). Most of the cases were Weber B fractures (38%) following an in-patient stay from 51 ± 4.3 days after primary treatment and 77 ± 10.0 days after secondary treatment in our hospital. Microbiological specimen showed in 77% Staphylococcus aureus with following intravenous antibiotic treatment for 13.9 ± 3.1 days in mean. Common comorbidities/risk factors were cardiovascular disease (28%), smoking (15%), and diabetes (18%). Cure of infection and clinical and radiographic osseous consolidation could be documented for all cases. Patients with implant-associated infections had significantly more risk factors than infection-free patients (1.1/0.33; p = .02 per patient). The matched-pair group showed significantly better long-term outcome in mean regarding the Ankle Osteoarthritis Score (2.0 ± 1.2/13.9 ± 4.7) and AOFAS hindfoot score (96.7 ± 1.9/87.3 ± 3.4). CONCLUSION: Immediate revision surgery with aggressive debridement, microbiological diagnostics, antibiotic therapy, and use of a drain until osseous consolidation is reached with following removal of the implant in patients with implant-associated infections after ankle fracture and open reduction internal fixation lead to cure of infection and fair long-term outcome in all cases. Special care must be taken of risk factors like diabetes and smoking. TRIAL REGISTRATION: 24/2008BO2.

Age-dependent risk factors for malnutrition in traumatology and orthopedic patients.

OBJECTIVE: The aim of this study was to investigate the prevalence of risk of malnutrition (RoM) in an orthopedic and traumatology patient cohort with a broad range of ages. In addition to the classical indicators for risk assessment (low body mass index, weight loss, and comorbidity), this study aimed to analyze the effects of lifestyle factors (eating pattern, smoking, physical activity) on RoM. METHODS: The prospective cohort study included 1053 patients in a level 1 trauma center in Germany. RoM was assessed by Nutritional Risk Screening (NRS) 2002 and for the elderly additionally by Mini Nutritional Assessment (MNA). Age-dependent risk factors identified in univariate statistical analysis were used for multivariate logistic regression models. RESULTS: The prevalence of patients at RoM (NRS ≥3) was 22%. In the three age categories (<50 y, 50-69 y, and ≥70 y), loss of appetite, weight loss, number of comorbidities, drugs and gastrointestinal symptoms significantly increased RoM in univariate statistical analysis. In patients ages ≥70 y, several disease- and lifestyle-related factors (not living at home, less frequent consumption of vegetables and whole meal bread, low physical activity, and smoking) were associated with RoM. Multivariate logistic regression model for the total study population identified weight loss (odds ratio [OR], 6.09; 95% confidence interval [CI], 4.14-8.83), loss of appetite (OR, 3.81; 95% CI, 2.52-5.78), age-specific low BMI (OR, 1.87; 95% CI, 1.18-2.97), number of drugs taken (OR, 1.19; 95% CI, 1.12-1.26), age (OR, 1.03; 95% CI, 1.02-1.04), and days per week with vegetable consumption (OR, 0.938; 95% CI, 0.89-0.99) as risk factors. CONCLUSION: Malnutrition in trauma and orthopedic patients is not only a problem related to age. Lifestyle-related factors also contribute significantly to malnutrition in geriatric patients.

Malnutrition - An underestimated factor in the inpatient treatment of traumatology and orthopedic patients: A prospective evaluation of 1055 patients.

INTRODUCTION: Suboptimal nutritional status is often observed among hospitalized patients across all medical specialties. The objective of the present study was to (1) analyze the prevalence of malnutrition in hospitalized orthopedic and trauma patients and (2) to evaluate the relationship between malnutrition and selected clinical outcomes. MATERIALS AND METHODS: The prospective field study was conducted between 06/2014 and 06/2015 in a German level I trauma center (Department of Traumatology, Septic Trauma Surgery and Arthroplasty) with a total number of 1055 patients. At hospital admission, patients were checked for malnutrition using the validated Nutritional Risk Screening (NRS). Patients at risk for malnutrition were defined as NRS≥3. Quality of life (SF-36) was assessed to evaluate the physical and mental health status prior to hospitalization. Clinical outcomes under consideration included 1) rate of adverse events, 2) length of hospitalization, and 3) mobilization after operative and conservative treatment. Patients were included independently of surgical intervention or age. RESULTS: 22.3% (235) of our patients were at risk for malnutrition (NRS≥3) while a regular nutritional status (NRS<3) was diagnosed in 77.7% (819). The highest prevalence of malnutrition was found in Septic Surgery with 31.0% (106), followed by Traumatology with 19.2% (100) and Arthroplasty with 15.1% (29). Higher prevalence of malnutrition was observed among patients with typical fractures of the elderly, such as lumbar spine and pelvis (47.4%), proximal femur (36.4%) and proximal humeral (26.7%) fractures. Furthermore, patients at risk for malnutrition showed prolonged hospitalization (13.7±11.1 vs. 18.2±11.7days), delayed postoperative mobilization (2.2±2.9 vs. 4.0±4.9days) and delayed mobilization after conservative treatment (1.1±2.7 vs. 1.8±1.9days). A statistically significant correlation of NRS with each parameter (Spearman's rank correlation, p<0.05) was observed. The incidence of adverse events in patients at risk for malnutrition was statistically significantly higher compared to that of patients with a regular nutritional status (37.2% vs. 21.1%, p<0.001). CONCLUSIONS: Malnutrition is widespread regarding hospitalized patients in the field of orthopedic and trauma surgery and results in suboptimal clinical outcome. It should be considered as an important factor that significantly contributes to delayed recovery. Especially elderly trauma patients and patients suffering from postoperative infections should be monitored carefully during hospitalization.

BMP9 a possible alternative drug for the recently withdrawn BMP7? New perspectives for (re-)implementation by personalized medicine.

Promotion of rhBMP2 and rhBMP7 for the routine use to support fracture healing has been hampered by high costs, safety concerns and reasonable failure rates, imposing restrictions in its clinical use. Since there is little debate regarding its treatment potential, there is rising need for a better understanding of the mode of action of these BMPs to overcome its drawbacks and promote more efficacious treatment strategies for bone regeneration. Recently, BMP9, owing to its improved osteogenic potential, is gaining attention as a promising therapeutic alternative. Our study aimed at identifying specific gene expression patterns which may predict and explain individual responses to rhBMP7 and rhBMP9 treatments. Therefore, we investigated the effect of rhBMP7 and rhBMP9 on primary human osteoblasts from 110 donors and corresponding THP-1-derived osteoclasts. This was further compared with each other and our reported data on rhBMP2 response. Based on the individual donor response, we found three donor groups profiting from rhBMP treatment either directly via stimulation of osteoblast function or viability and/or indirectly via inhibition of osteoclasts. The response on rhBMP7 treatment correlated with expression levels of the genes BAMBI, SOST, Noggin, Smad4 and RANKL, while the response of rhBMP9 correlated to the expression levels of Alk6, Endoglin, Smurf1, Smurf2, SOST and RANKL in these donors. Noteworthy, rhBMP9 treatment showed significantly increased osteogenic activity (AP activity and Smad nuclear translocation) when compared to the two clinically used rhBMPs. Based on patient's respective expression profiles, clinical application of rhBMP9 either solely or in combination with rhBMP2 and/or rhBMP7 can become a promising new approach to fit the patient's needs to promote fracture healing.

Crucial Role of Vitamin D in the Musculoskeletal System.

Vitamin D is well known to exert multiple functions in bone biology, autoimmune diseases, cell growth, inflammation or neuromuscular and other immune functions. It is a fat-soluble vitamin present in many foods. It can be endogenously produced by ultraviolet rays from sunlight when the skin is exposed to initiate vitamin D synthesis. However, since vitamin D is biologically inert when obtained from sun exposure or diet, it must first be activated in human beings before functioning. The kidney and the liver play here a crucial role by hydroxylation of vitamin D to 25-hydroxyvitamin D in the liver and to 1,25-dihydroxyvitamin D in the kidney. In the past decades, it has been proven that vitamin D deficiency is involved in many diseases. Due to vitamin D's central role in the musculoskeletal system and consequently the strong negative impact on bone health in cases of vitamin D deficiency, our aim was to underline its importance in bone physiology by summarizing recent findings on the correlation of vitamin D status and rickets, osteomalacia, osteopenia, primary and secondary osteoporosis as well as sarcopenia and musculoskeletal pain. While these diseases all positively correlate with a vitamin D deficiency, there is a great controversy regarding the appropriate vitamin D supplementation as both positive and negative effects on bone mineral density, musculoskeletal pain and incidence of falls are reported.

First mid-term results after cancellous allograft vitalized with autologous bone marrow for infected femoral non-union.

BACKGROUND: Surgical treatment of infected femoral non-union is challenging. Only few reports exist including autologous bone grafting (ABG) from the iliac crest promoting union. Vitalized allogeneic bone grafting (VABG) is an alternative promoting osseous healing and reconstructing bone defects. VABG contains allogeneic cancellous bone, impregnated with autologous bone marrow puncture harvested from the iliac crest. Yet, no systematic trial exists summarizing the results of septic femoral non-union using VABG analyzing the infection eradication rate, rate of osseous integration with union, and osseous remodeling. METHODS: In this prospective non-randomized cohort study, 18 patients treated by nailing or plating for femur fractures that subsequently developed a septic non-union were included. The surgical intervention included a standardized protocol by eradicating infection first, followed by implantation VABG to promote osseous union. Main outcome measurements were radiographic union and clinical parameters. RESULTS: Mean follow-up was 5.9 years (range: 2-8 years). Infection eradication was achieved for all patients, while union was achieved in 15 out of 18 cases (83.3 %). Mean time for union took 16.9 weeks (range: 12-24). Radiographic analysis proved osseous remodeling and full integration of VABG within 12 months for 15 patients. No infection recurrence occurred at final follow-up. CONCLUSIONS: VABG demonstrated a high union rate without donor site morbidity as the main advantage over ABG. Sufficient osseous integration within 3 months and remodeling within 12 months are promising aspects, as no late fatigue fractures occurred. However, further trials are necessary due to the limitations of this study.

Factors circulating in the blood of type 2 diabetes mellitus patients affect osteoblast maturation - description of a novel in vitro model.

Type 2 diabetes mellitus (T2DM) is one of the most frequent metabolic disorders in industrialized countries. Among other complications, T2DM patients have an increased fracture risk and delayed fracture healing. We have demonstrated that supraphysiological glucose and insulin levels inhibit primary human osteoblasts׳ maturation. We aimed at developing a more physiologically relevant in vitro model to analyze T2DM-mediated osteoblast changes. Therefore, SCP-1-immortalized pre-osteoblasts were differentiated with T2DM or control (non-obese and obese) sera. Between both control groups, no significant changes were observed. Proliferation was significantly increased (1.69-fold), while AP activity and matrix mineralization was significantly reduced in the T2DM group. Expression levels of osteogenic marker genes and transcription factors were altered, e.g. down-regulation of RUNX2 and SP-7 or up-regulation of STAT1, in the T2DM group. Active TGF-ß levels were significantly increased (1.46-fold) in T2DM patients׳ sera. SCP-1 cells treated with these sera showed significantly increased TGF-ß signaling (2.47-fold). Signaling inhibition effectively restored osteoblast maturation in the T2DM group. Summarizing our data, SCP-1 cells differentiated in the presence of T2DM patients׳ serum exhibit reduced osteoblast function. Thus, this model has a high physiological impact, as it can identify circulating factors in T2DM patients׳ blood that may affect bone function, e.g. TGF-ß.

Effect of metallo-ß-lactamase production and multidrug resistance on clinical outcomes in patients with Pseudomonas aeruginosa bloodstream infection: a retrospective cohort study.

BACKGROUND: Blood stream infections (BSI) with Pseudomonas aeruginosa lead to poor clinical outcomes. The worldwide emergence and spread of metallo-ß-lactamase (MBL) producing, often multidrug-resistant organisms may further aggravate this problem. Our study aimed to investigate the effect of MBL-producing P. aeruginosa (MBL-PA) and various other resistance phenotypes on clinical outcomes. METHODS: A retrospective cohort study was conducted in three German hospitals. Medical files from 2006 until 2012 were studied, and a number of 113 patients with P. aeruginosa BSI were included. The presence of VIM, IMP and NDM genes was detected using molecular techniques. Genetic relatedness was assessed through multilocus sequence typing (MLST). The effect of resistance patterns or MBL production on clinical outcomes was investigated by using multivariate Cox regression models. RESULTS: In-hospital mortality was significantly higher in patients with MBL-PA and multidrug-resistant P. aeruginosa. However, neither BSI with MBL-PA nor BSI with various resistance phenotypes of P. aeruginosa were independently associated with mortality or length of hospital stay. In multivariate models, the SAPS II score (HR 1.046), appropriate definitive treatment (HR range 0.25-0.26), and cardiovascular disease (HR range 0.44-0.46) were independent predictors of mortality. Concomitant infections were associated with an excess length of stay (HR < 1). CONCLUSIONS: Medication with appropriate antimicrobial agents at any time during the course of infection remains the key for improving clinical outcomes in patients with P. aeruginosa BSI and should be combined with a strict implementation of routine infection control measures.

Time to positivity as prognostic tool in patients with Pseudomonas aeruginosa bloodstream infection.

OBJECTIVES: The time to positivity (TTP), measured as the time span between the start of incubation and the alert signal from the blood culture device, has been described as useful tool of prognosis in patients suffering from blood stream infection with Staphylococcus aureus, Escherichia coli and Klebsiella pneumonia. The present study investigates the relationship between TTP and in-hospital mortality in patients with monomicrobial Pseudomonas aeruginosa blood stream infection (PA-BSI). METHODS: From 2006 until 2012 a retrospective cohort study was undertaken in 3 hospitals in the region surrounding Tübingen, Germany. Seventy-four patients with monomicrobial PA-BSI were studied. TTP and clinical parameters were determined and analyzed by receiver operating characteristic (ROC) analysis and Cox regression. RESULTS: The in-hospital mortality of our clinical cohort was 33.78%. In multivariate Cox regression, a TTP ≤ 18 h proved to be independently associated with mortality (HR 3.83, P = 0.012) along with SAPS II score (HR 1.04, P = 0.006), cardiac disease (HR 0.33, P = 0.008) and appropriate definitive antimicrobial treatment (HR 0.21, P = 0.013). CONCLUSIONS: TTP is an easy-to-measure laboratory tool for prognosis in patients with monomicrobial PA-BSI, providing useful information in addition to clinical parameters.

Elution kinetics, antimicrobial efficacy, and degradation and microvasculature of a new gentamicin-loaded collagen fleece.

Management of bone and soft tissue infections generally includes surgical procedures as well as attendant treatment and prevention with gentamicin-loaded fleeces. Conventional gentamicin-containing collagen fleeces currently in use are strongly acidic and exhibit limited biocompatibility thereby adversely affecting wound healing. To improve the antibiotic delivery system, a new phosphate-buffered, gentamicin-loaded fleece with pH-neutral properties has been developed (Jason G). This study aimed at comparing the elution kinetics of gentamicin release and the antimicrobial efficacy of conventional fleeces with the newly developed fleece in vitro. In addition, degradation and microvasculature of implanted fleeces were examined in a rat model and assessed using histology, as well as detection of ED-1 and PECAM-expression using immunohistochemistry. We show that the phosphate-buffered fleeces have reduced release (p < 0.05) of the integrated gentamicin. However, all of the fleeces tested had a significant antimicrobial effect on the growth of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa strains (p < 0.01). Among the fleeces tested, the new Jason G fleece had the weakest but nevertheless sufficient antimicrobial effectiveness. Evaluation of the antibiotic effect in the prevention of an infection showed no differences between the applied fleeces. Following surgical implantation of fleece in the backs of Wistar rats we observed, on day 5 after implantation, an increase in cell infiltration and microvascularization with the phosphate-buffered fleece as compared with conventional fleeces, which show necrotic cells on their surface. Unlike the acidic fleeces, on day 15 after implantation the pH-neutral fleece was resorbed widely. Here, we show that the new, pH-neutral, gentamicin-containing fleece Jason G exhibits good overall antimicrobial effectiveness against both gram-positive and gram-negative bacteria in vitro with improved degradation properties and microvasculature formation in vivo.

New blood vessel formation and expression of VEGF receptors after implantation of platelet growth factor-enriched biodegradable nanocrystalline hydroxyapatite.

Vascular endothelial growth factor (VEGF) plays a key role for the interaction of osteoblasts and endothelial cells and, therefore, is an important factor for the osteointegration of bone substitutes. The aim of the current work was to study the effects of platelet growth factors (PLF) on new blood vessel formation and VEGF-receptors expression pattern in bone defects filled with nanocrystalline hydroxyapatite (HA) paste in miniature-pigs. Conventional histology, RT-PCR for VEGF and receptors mRNA, Western blot analysis, immunohistochemical staining and quantitative assessment of newly formed vessels was performed. HA enriched with platelet growth factor (HA/PLF+) led to an up-regulation of VEGF-R1 synthesis, a slightly enhanced number of newly formed vessels with higher sprouting activity compared with HA without PLF (HA/PLF-) filling defects. These observation are most likely attributable to a stimulating effect of TGF-ss from the platelet factor on VEGF expression in osteoblasts.

Subcapsular liver hematoma in HELLP syndrome: Evaluation of diagnostic and therapeutic options--a unicenter study.

OBJECTIVE: Subcapsular liver hematoma formation has been reported in less than 2% of pregnancies complicated by HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome. The purpose of this study was to identify the main diagnostic and therapeutic options for management of these patients. STUDY DESIGN: In this 10-year retrospective review, we performed a computer-directed search of all cases of confirmed HELLP syndrome with hepatic hematoma treated in the surgical department of our tertiary care referral medical center. RESULTS: Five patients with subcapsular liver hematoma in HELLP syndrome could be identified. All patients received transabdominal ultrasound, computed tomography, or magnetic resonance imaging. Conservative treatment was successful in three patients. Emergency surgical intervention was necessary in two patients, including one liver transplantation. CONCLUSION: The case series shows the full diagnostic spectrum with transabdominal ultrasound, computed tomography, and magnetic resonance imaging, as well as the different therapeutic options varying from conservative therapy to operative management, including liver transplantation.