Bioactive adrenomedullin (bio-ADM) is associated with endothelial dysfunction in infants and children with complex congenital heart disease undergoing open-heart surgery on cardiopulmonary bypass.

OBJECTIVES: Children with congenital heart disease (CHD) undergoing cardiac surgery on cardiopulmonary bypass (CPB) are at risk for systemic inflammation leading to endothelial dysfunction associated with increased morbidity. Bioactive adrenomedullin (bio-ADM) is a peptide regulating vascular tone and endothelial permeability. The aim of this study was to evaluate the dynamics of plasma bio-ADM in this patient cohort and its role in capillary leak. METHODS: Plasma samples from 73 pediatric CHD patients were collected for bio-ADM measurement at five different timepoints (TP) in the pre-, intra-, and post-operative period. The primary endpoint was a net increase in bio-ADM levels after surgery on CPB. Secondary endpoints included association of bio-ADM levels with clinical signs for endothelial dysfunction. RESULTS: Bio-ADM levels increased after surgery on CPB from pre-operative median of 12 pg/mL (IQR [interquartile range] 12.0-14.8 pg/mL) to a maximum post-operative median of 48.8 pg/mL (IQR 34.5-69.6 pg/mL, p<0.001). Bio-ADM concentrations correlated positively with post-operative volume balance, (r=0.341; p=0.005), increased demand for vasoactive medication (duration: r=0.415; p<0.001; quantity: TP3: r=0.415, p<0.001; TP4: r=0.414, p<0.001), and hydrocortisone treatment for vasoplegia (bio-ADM median [IQR]:129.1 [55.4-139.2] pg/mL vs. 37.9 [25.2-64.6] pg/mL; p=0.034). Patients who required pleural effusion drainage revealed higher bio-ADM levels compared to those who did not (median [IQR]: 66.4 [55.4-90.9] pg/mL vs. 40.2 [28.2-57.0] pg/mL; p<0.001). CONCLUSIONS: Bio-ADM is elevated in children after cardiac surgery and higher levels correlate with clinical signs of capillary leakage. The peptide should be considered as biomarker for endothelial dysfunction and as potential therapeutic target in this indication.

B-nor-methylene Colchicinoid PT-100 Selectively Induces Apoptosis in Multidrug-Resistant Human Cancer Cells via an Intrinsic Pathway in a Caspase-Independent Manner.

Colchicine, the main active alkaloid from Colchicum autumnale L., is a potent tubulin binder and represents an interesting lead structure for the development of potential anticancer chemotherapeutics. We report on the synthesis and investigation of potentially reactive colchicinoids and their surprising biological activities. In particular, the previously undescribed colchicinoid PT-100, a B-ring contracted 6-exo-methylene colchicinoid, exhibits extraordinarily high antiproliferative and apoptosis-inducing effects on various types of cancer cell lines like acute lymphoblastic leukemia (Nalm6), acute myeloid leukemia (HL-60), Burkitt-like lymphoma (BJAB), human melanoma (MelHO), and human breast adenocarcinoma (MCF7) cells at low nanomolar concentrations. Apoptosis induction proved to be especially high in multidrug-resistant Nalm6-derived cancer cell lines, while healthy human leukocytes and hepatocytes were not affected by the concentration range studied. Furthermore, caspase-independent initiation of apoptosis via an intrinsic pathway was observed. PT-100 also shows strong synergistic effects in combination with vincristine on BJAB and Nalm6 cells. Cocrystallization of PT-100 with tubulin dimers revealed its (noncovalent) binding to the colchicine-binding site of ß-tubulin at the interface to the α-subunit. A pronounced effect of PT-100 on the cytoskeleton morphology was shown by fluorescence microscopy. While the reactivity of PT-100 as a weak Michael acceptor toward thiols was chemically proven, it remains unclear whether this contributes to the remarkable biological properties of this unusual colchicinoid.

Evaluation of pain susceptibility by taking blood pressure in patients with infections: A prospective comparative study.

ABSTRACT: Pain sensitization leading to polyalgia can be observed during infectious diseases. The blood pressure cuff-evoked pain threshold (BPCEPT) has been used in previous studies as a screening tool for fibromyalgia.We aimed to use the BPCEPT as a screening test for detecting pain sensitization in patients suffering from infectious diseases. We also investigated whether specific factors were associated with pain sensitization.We performed a prospective comparative study including all patients of our infectious diseases center in a 1-year period. We created a positive control group of patients suffering from fibromyalgia and a negative control group of "apparently healthy" patients consulting for vaccination.The blood pressure (BP) cuff was inflated until the patient signaled that they experienced pain, and this pressure value was noted.A total of 2355 patients were included. The positive control group had significantly lower values of the BPCEPT than all other groups. Among hospitalized patients with infectious diseases, a low BPCEPT was significantly associated with high temperature (P < .0001), older age (P = .002), being a woman (P = .004), high serum glutamic-oxaloacetic transaminase (P = .007), and high C reactive protein levels (P = .02). Moreover, in multivariate analysis, respiratory infection, meningitis, urinary tract infection, febrile neutropenia, and Q fever were independently associated with a low BPCEPT. A significant negative dynamic correlation between the BPCEPT and temperature was also observed (P < .001).We demonstrated for the first time in a large sample of patients that the BPCEPT method can be used to detect pain susceptibility. We observed a significant dynamic correlation between pain sensitization and temperature. Additionally, pain sensitization was associated with some diseases, suggesting that they trigger pain sensitivity.

Preoperative simplified geriatric assessment in planned hip and knee arthroplasty.

INTRODUCTION: Hip and knee arthroplasties are the most common planned orthopedic surgical procedures in older persons. It would be useful to identify frailties before surgery to improve the outcome of older patients. PURPOSE: The objective of this work was to identify the criteria of a simplified comprehensive geriatric assessment (mini-CGA) that were associated with unplanned hospital readmission and postoperative complications within 3 months after the planned hip and/or knee arthroplasty in patients ≥ 65 years. METHODS: This prospective study was carried out in the orthopedic department of Marseille University Hospital from January to May 2019. A mini-CGA was performed preoperatively. RESULTS: One hundred four patients were included in the study. The rate of early readmission within 3 months after surgery was 12.5% and the rate of postoperative complications was 40.4%. In multivariate analysis, dependence in the activities of daily living (ADL ≤ 5) was the only factor associated with unplanned readmission (aOR = 9.9, 95% CI 1.9-50.8), and living alone was the only factor associated with postoperative complications (aOR = 3.2, 95% CI 1.2-8.8). CONCLUSIONS: We found that the ADL score was associated with the risk of unplanned readmission in older patients undergoing planned arthroplasty, and that living alone was associated with postoperative complications. A preoperative mini-CGA appears essential to limit postoperative morbidity.

Solid-Contact Ion-Selective and Reference Electrodes Covalently Attached to Functionalized Poly(ethylene terephthalate).

Numerous ion-selective and reference electrodes have been developed over the years. Following the need for point-of-care and wearable sensors, designs have transitioned recently from bulky devices with an aqueous inner filling solution to planarizable solid-contact electrodes. However, unless the polymeric sensing and reference membranes are held in place mechanically, delamination of these membranes from the underlying solid to which they adhere physically limits sensor lifetime. Even minor external mechanical stress or thermal expansion can result in membrane delamination and, thereby, device failure. To address this problem, we designed a sensing platform based on poly(ethylene terephthalate) substrates to which polyacrylate-based sensing and polymethacrylate-based reference membranes are attached covalently. Ion-selective membranes with covalently attached or freely dissolved ionophore- and ionic-liquid-doped reference membranes can be directly photopolymerized onto surface-functionalized poly(ethylene terephthalate), resulting in the formation of covalent bonds between the underlying substrate and the attached membranes. H+- and K+-selective electrodes thus prepared exhibit highly selective responses with the theoretically expected (Nernstian) response slope, and reference electrodes provide sample-independent reference potentials over a wide range of electrolyte concentrations. Even repeated mechanical stress does not result in the delamination of the sensing and reference membranes, leading to electrodes with much improved long-term performance. As demonstrated for poly(ethylene-co-cyclohexane-1,4-dimethanol terephthalate) (PETG), this approach may be expanded to a wide range of other polyester, polyamide, and polyurethane platform materials. Covalent attachment of sensing and reference membranes to an inert plastic platform material is a very promising approach to a problem that has plagued the field of ion-selective electrodes and field effect transistors for over 30 years.

Cervical osteomyelitis: A new identity of dreaded complication following pharyngeal cancer treatment.

BACKGROUND: Cervical osteomyelitis following the treatment of pharyngeal cancer with laryngectomy and chemoradiotherapy is poorly reported. METHODS: Six cases of cervical osteomyelitis occurring over a 1-year period are described herein. These are reviewed alongside four cases reported previously in the literature. RESULTS: Among the total 10 cases, the average age of the patients was 58.7 years. The period between laryngectomy and the diagnosis of cervical osteomyelitis was on average 3 years and 1 month and the male to female sex ratio was 9:1. Two patients had a history of cervical fistula with an esophageal prosthesis, one had a spontaneous cervical fistula, one had a pharyngeal cutaneous fistula, and one had an esophageal prosthesis without any fistula. At the time of diagnosis, seven had a history of cervical pain (70%) and nine had a neurological deficit (90%). Seven patients (70%) underwent surgery; one (10%) was contraindicated for a general anesthetic and two (20%) died before any intervention. The indication for surgery was a neurological deficit for six patients (60%) and the requirement for lavage and debridement for two patients (20%). The average length of antimicrobial treatment was 12.7 weeks. The outcome was favorable for six patients. Four patients died. CONCLUSIONS: Cervical osteomyelitis is a serious but rarely reported complication following the treatment of pharyngeal cancer with chemoradiotherapy and laryngectomy. Cervical pain was the first sign to appear, sometimes 1year before any other sign. Physicians should be aware of this dreaded complication, which is probably underdiagnosed and is related to an increased mortality rate.

Synthesis and biological evaluation of novel non-racemic indole-containing allocolchicinoids.

Two novel indole-containing allocolchicinoids were prepared from naturally occurring colchicine exploiting the Curtius rearrangement and tandem Sonogashira coupling/Pd-catalyzed cyclization as the key transformations. Their cytotoxic properties, apoptosis-inducing activity, tubulin assembly inhibition and short-time cytotoxic effects were investigated. Compound 7 demonstrated the most pronounced anti-cancer activity: IC50 < 1 nM, cell cycle arrest in the G2/M phase, 25% apoptosis induction, as well as lower destructive short-time effects on HT-29 cell line in comparison with colchicine. Docking studies for prepared indole-derived allocolchicine analogues were carried out.

Prosthetic joint infection caused by Granulicatella adiacens: a case series and review of literature.

BACKGROUND: Bone and joint infection involving Granulicatella adiacens is rare, and mainly involved in cases of bacteremia and infectious endocarditis. Here we report three cases of prosthetic joint infection involving G. adiacens that were successfully treated with surgery and prolonged antimicrobial treatment. We also review the two cases of prosthetic joint infection involving G. adiacens that are reported in the literature. CASE PRESENTATION: Not all five cases of prosthetic joint infection caused by G. adiacens were associated with bacteremia or infectious endocarditis. Dental care before the onset of infection was observed in two cases. The median time delay between arthroplasty implantation and the onset of infection was of 4 years (ranging between 2 and 10 years). One of our cases was identified with 16srRNA gene sequencing, one case with MALDI-TOF mass spectrometry, and one case with both techniques. Two literature cases were diagnosed by 16srRNA gene sequencing. All five cases were cured after surgery including a two-stage prosthesis exchange in three cases, a one-stage prosthesis exchange in one case, and debridement, antibiotics, irrigation, and retention of the prosthesis in one case, and prolonged antimicrobial treatment. CONCLUSION: Prosthetic joint infection involving G. adiacens is probably often dismissed due to difficult culture or misdiagnosis, in particular in the cases of polymicrobial infection. Debridement, antibiotics, irrigation, and retention of the prosthesis associated with prolonged antimicrobial treatment (≥ 8 weeks) should be considered as a treatment strategy for prosthetic joint infection involving G. adiacens.

Assembly of dicobalt and cobalt-aluminum oxide clusters on metal-organic framework and nanocast silica supports.

NU-1000, a mesoporous metal-organic framework (MOF) featuring hexazirconium oxide nodes and 3 nm wide channels, was infiltrated with a reactive dicobalt complex to install dicobalt active sites onto the MOF nodes. The anchoring of the dicobalt complex onto NU-1000 occurred with a nearly ideal stoichiometry of one bimetallic complex per node and with the cobalt evenly distributed throughout the MOF particle. To access thermally robust multimetallic sites on an all-inorganic support, the modified NU-1000 materials containing either the dicobalt complex, or an analogous cobalt-aluminum species, were nanocast with silica. The resulting materials feature Co2 or Co-Al bimetallated hexazirconium oxide clusters within a silica matrix. The cobalt-containing materials are competent catalysts for the selective oxidation of benzyl alcohol to benzaldehyde. Catalytic activity depends on the number of cobalt ions per node, but does not vary significantly between the NU-1000 and silica supports. Hence, the multimetallic oxide clusters remain site-isolated and substrate-accessible within the nanocast materials.

Staphylococcus lugdunensis: a neglected pathogen of infections involving fracture-fixation devices.

PURPOSE: Cases of fracture-fixation device infection involving Staphylococcus lugdunensis are not frequent. The clinical characteristics and the choice of treatment strategies of these infections are not obviously known to date. METHODS: We performed a review of fracture-fixation device infection involving S. lugdunensis managed by our centres. RESULTS: Among the 38 cases of fracture-fixation device infection involving S. lugdunensis, 53% were located in the tibia. Most of our cases (87%) were chronic infections. Purulent discharge, which occurred in 79% of cases, was the most frequent clinical symptom, followed by pain in 63%, local inflammation in 55%, and fever in 37%. Bacteremia and severe sepsis occurred in 10% and 18% of cases, respectively. Four cases (10%) were treated exclusively with antimicrobial treatment alone. Thirty-four cases (89%) were treated with a combination of surgery with antimicrobial therapy including surgical debridement, antibiotics and osteosynthesis device retention in six cases (16%), and osteosynthesis device removal in 27 cases (71%). The mean length of antibiotic treatment was 119 days. The relapse rate was high that was not related to selection of resistant strains. Polymicrobial infection had no impact on clinical outcome. A combination of surgery with antimicrobial therapy was identified as a significant prognostic factor associated with remission (p = 0.042). CONCLUSIONS: S. lugdunensis is probably involved in more infections than has been reported. Using appropriate microbiological methods laboratories should routinely identify the species of all coagulase-negative Staphylococci isolates involved in fracture-fixation device infection to better achieve the treatment strategies of fracture-fixation device infection involving S. lugdunensis.

Feasibility and Acceptability of Anal Self-Sampling for Human Papillomavirus Screening in HIV-Infected Patients.

OBJECTIVES: Anal cancer incidence is increasing among HIV-positive patients. No consensus currently exists for the screening of anal dysplasia. This study aimed at evaluating the feasibility and acceptability of anal self-sampling and assessing the prevalence of human papillomavirus (HPV) types among HIV-positive patients from Marseille University Hospitals. METHODS: Between October 2013 and March 2014, during their regular visits for the monitoring of their HIV infection in an HIV outpatient clinical unit of Marseille University Hospitals, patients were asked to self-sample anal swabs for HPV detection. A specimen self-collection kit was provided. HPV detection and genotyping were performed using in-house protocols. The quality of self-sampling was assessed by concurrent cellular quantification in collected samples. RESULTS: The acceptability rate of anal self-sampling was 91%, and 91% of the self-sampled specimens were appropriate for HPV screening. In addition, 76% of the samples were positive for HPV, including 54% of HPV types with oncogenic potential. CONCLUSIONS: This study indicates that HPV detection and typing through anal self-sampling is a valuable strategy to screen patients at high risk for anal cancer development. This could allow earlier management of anal lesions and related cancer in patients at high risk for HPV.

Late infectious endocarditis of surgical patch closure of atrial septal defects diagnosed by 18F-fluorodeoxyglucose gated cardiac computed tomography (18F-FDG-PET/CT): a case report.

BACKGROUND: In contrast to percutaneous atrial septal occluder device, surgical patch closure of atrial defects was known to be no infective endocarditis risk. CASE PRESENTATION: We herein report the first case of late endocarditis of surgical patch closure of atrial septal defects occurred at 47-year after surgery. On September 2014, a 56-year-old immunocompetent French Caucasian man was admitted into the Emergency Department for 3-week history of headache, acute decrease of psychomotor performance and fever at 40 °C. The diagnosis has been evoked during his admission for the management of a brain abscess and confirmed using 18F-fluorodeoxyglucose gated cardiac computed tomography (18F-FDG-PET/CT). Bacterial cultures of surgical deep samples of brain abscess were positive for Streptococcus intermedius and Aggregatibacter aphrophilus as identified by the matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry and confirmed with 16S rRNA gene sequencing. The patient was treated by antibiotics for 8 weeks and surgical patch closure removal. CONCLUSIONS: In summary, late endocarditis on surgical patch and on percutaneous atrial septal occluder device of atrial septal defects is rare. Cardiac imaging by the 18F-fluorodeoxyglucose gated cardiac computed tomography (18F-FDG-PET/CT) could improve the diagnosis and care endocarditis on surgical patch closure of atrial septal defects while transthoracic and transesophageal echocardiography remained difficult to interpret.

Salmonella enterica serovar Enteritidis brain abscess mimicking meningitis after surgery for glioblastoma multiforme: a case report and review of the literature.

BACKGROUND: Salmonella brain abscess associated with brain tumor is rare. Only 11 cases have been reported to date. Here we report a case of brain abscess caused by Salmonella enterica serovar Enteritidis mimicking post-surgical meningitis in a patient with glioblastoma multiforme. CASE PRESENTATION: A 60-year-old Algerian woman was admitted through an emergency department for a 4-day history of headache, nausea and vomiting, and behavioral disorders. Surgery for cerebral tumor excision was performed and histopathological analysis revealed glioblastoma multiforme. On the seventh day post-surgery, she presented a sudden neurological deterioration with a meningeal syndrome, confusion, and fever of 39.8°C. Her cerebrospinal fluid sample and blood cultures were positive for S. enterica Enteritidis. She was treated with ceftriaxone and ciprofloxacin. On the 17th day post-surgery, she presented a new neurological disorder and purulent discharge from the surgical wound. Brain computed tomography revealed a large cerebral abscess located at the operative site. Surgical drainage of the abscess was performed and microbial cultures of surgical deep samples were positive for the same S. enterica Enteritidis isolate. She recovered and was discharged 6 weeks after admission. CONCLUSIONS: In this case report, a brain abscess was initially diagnosed as Salmonella post-surgical meningitis before the imaging diagnosis of the brain abscess. The diagnosis of brain abscess should be considered in all cases of non-typhoidal Salmonella meningitis after surgery for brain tumor. Surgical brain abscess drainage followed by prolonged antibiotic treatment remains a major therapeutic option.

Changing trends in the epidemiology of vertebral osteomyelitis in Marseille, France.

The incidence and significant morbidity of vertebral osteomyelitis are increasing despite the progress of diagnosis competences. Among the 50 cases of vertebral osteomyelitis managed in our centers over the past 5 years, 84% of the cases were in men. The mean age was 55 years. Sixty-two percent of patients had comorbidities and risk factors: diabetes mellitus (24%), malignancy (16%), intravenous drug use (10%) and alcoholism (4%). A source of infection was identified in 66% of cases, including postvertebral surgery infection (18%) and hematogenous infection (48%). The mean time to diagnosis was 36 days. Back pain were occurred in 90% of cases, fever (70%), neurologic deficits (40%), epidural abscesses (32%), completed vertebral bone destruction (26%) and psoas abscess (12%). A single organism was isolated in 92% of cases. Gram-positive bacteria were identified in 76% of cases, while Gram-negative bacilli (GNB) were found in 18% of cases. The presence of GNB was significantly associated with malignancy (p 0.041). The mean duration of antibiotic therapy was 123 days. Surgical treatment was performed in 41 cases: spinal stabilization (26%), drainage of abscesses (32%) and relief of compression (40%). Residual pain was found in 24% of cases, and neurologic sequelae in 22%. Cervical or thoracic localization was a risk factor for neurologic compromise (p 0.042). The epidemiology of vertebral osteomyelitis has changed; an increase in malignancy that was significantly associated with vertebral osteomyelitis due to GNB has been observed. Our study shows that the rate of neurologic complications remains high despite improved diagnostic capabilities and optimal treatment.

The microbial epidemiology of breast implant infections in a regional referral centre for plastic and reconstructive surgery in the south of France.

BACKGROUND: Breast implant infections are usually caused by Staphylococcus aureus and coagulase-negative staphylococci. Gram-negative bacilli are rarely reported to be involved in breast implant infections. METHODS: Thirty-seven cases of microbiologically confirmed breast implant infection managed from January 2008 to June 2012 in the study centre were reviewed, including 10 cases from the study centre itself and 27 cases from private clinics in the region. RESULTS: The prevalence of breast implant infection in the study centre was 0.74% of breast implantation, i.e., 3.23% in breast reconstruction for breast cancer and 0.27% in aesthetic breast augmentation (p=0.0002). Of the 37 cases, 30% had undergone radiotherapy and 11% had undergone a lymph node dissection. S. aureus was identified in 18 cases, Gram-negative bacilli in 10 cases, coagulase-negative staphylococci in eight cases, anaerobic bacteria in eight cases, and streptococci in three cases. Pseudomonas aeruginosa was the second most commonly identified pathogen. Staphylococcus epidermidis was the most frequent coagulase-negative Staphylococcus species. In addition to Propionibacterium acnes and Actinomyces neuii, other facultative and strict anaerobic bacteria have not been reported before, e.g., Bacteroides thetaiotaomicron, Corynebacterium simulans, Dermabacter hominis, Finegoldia magna, and Peptoniphilus harei. Seventy-percent of cases were treated by immediate implant removal. All cases treated only with antibiotics were treated with surgery at the second visit. CONCLUSIONS: The microbiological epidemiology was noted by an increasing the proportion of Gram-negative bacteria and anaerobic bacteria detected with the advent of MALDI-TOF MS and molecular identification for diagnosis.

Detection of the newly characterized HIV CRF56_cpx in Marseille, southeastern France.

OBJECTIVES: We aimed to seek HIV sequences highly similar to CRF56-cpx, a recently described newly circulating B/CRF02/G recombinant HIV, in our local clinical microbiology laboratory sequence database. METHODS: A recently implemented tool that combines a databank of all HIV nucleotide sequences obtained at our clinical microbiology laboratory with a search tool that uses BLAST was used. A comparative and phylogenetic analysis of HIV protease and reverse transcriptase fragments was performed. RESULTS: We identified two sequences that were clustered with CRF56-cpx with a bootstrap value of 99% in phylogenetic analyses; these were obtained from two patients diagnosed with HIV in 2009-2011. HIV protease-reverse transcriptase sequences obtained from these two patients shared a mean identity of 98.2±0.2% with previously described CRF56-cpx sequences. Both case patients diagnosed with HIV in our centre were highly sexually active men who have sex with men. CONCLUSIONS: Our findings highlight the continuous expansion of HIV diversity in France and indicate that real-time surveillance of HIV molecular epidemiology, including the comparison of sequences from laboratory, national, and international databases, might be helpful to identify the emergence, circulation, and transmission of viral strains.

Pseudoclavibacter-like subcutaneous infection: a case report.

BACKGROUND: Arthrobacter-like organisms, including Pseudoclavibacter organisms, have rarely been documented as being responsible for infection in humans. CASE PRESENTATION: An 81-year-old French man developed a subcutaneous infection despite antibiotic treatment combining clindamycin and metronidazole for chronic wound infection. A skin biopsy showed numerous polymorphonuclear cells and no bacteria, but a subcutaneous swab yielded numerous polymorphonuclear cells, a few Gram-positive cocci, Gram-negative cocci, and Gram-positive rods. The Gram-positive rod sequence exhibited 99% sequence similarity with uncultured Pseudoclavibacter sp. [GenBank:EF419350] and 99% sequence similarity with uncultured Pseudoclavibacter sp. [GenBank:EF419347]. The genetic data and unique peptide profile of this Pseudoclavibacter-like isolate, determined by matrix-assisted laser desorption ionization-time of flight mass spectrometry, underscored its uniqueness. CONCLUSIONS: Pseudoclavibacter-like organisms are identifiable in cutaneous and subcutaneous infections in humans.

Effects of G-CSF on systemic inflammation, coagulation and platelet activation in patients with acute myocardial infarction.

INTRODUCTION: In the prospective, randomised, double-blind, placebo-controlled Regenerate Vital Myocardium by Vigorous Activation of Bone Marrow Stem Cells (REVIVAL)-2 trial patients with acute myocardial infarction (AMI) and successful mechanical reperfusion received granulocyte-colony stimulating factor (G-CSF, 10 µg/kg KG s.c.) or placebo for 5 days. Aim of this substudy was to assess the impact of G-CSF on systemic inflammatory and procoagulant responses and platelet activation. METHODS AND RESULTS: Before and five days after G-CSF (n=56) or placebo (n=58) circulating cytokine concentrations of interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-12 and Tumor-Necrosis Factor-α (TNF-α were measured. Prothrombin fragment F1+2 and Tissue Factor activity served as a measure for activated coagulation. Platelet activation was characterized by cell surface expression of the activated fibrinogen receptor (PAC-1), P-selectin and CD40L by flow cytometry. Administration of G-CSF was associated with elevated TNF-α and CRP concentrations compared to the placebo group after 5 days. Other cytokines (IL-1ß, IL-6, IL-8, IL-10, IL-12) were comparable after treatment with G-SCF or placebo. Similarly, circulating prothrombin fragments F1+2, TF activity and platelet activation did not differ in both groups. CONCLUSION: Treatment with G-CSF in patients with AMI was associated with enhanced proinflammatory TNF-α and CRP levels but no activation of coagulation.