Prevalence of morphometric vertebral fractures in osteoporotic patients in Greece: the Vertebral Integrity Assessment (VERTINAS) study.

Our purpose was to assess the prevalence of morphometric vertebral fractures (VFs) in osteoporotic patients in our country. We found that 25.4% of patients had sustained a VF, and the majority of them (76.6%) were undiagnosed prior to inclusion in this study. INTRODUCTION: We assessed the prevalence of morphometric vertebral fractures (VFs) in osteoporotic patients in our country. METHODS: Patients were recruited via announcements by the national media, their attending physicians or the National patients' Society. Inclusion criteria were (1) age > 50 years, (2) postmenopausal status > 2 years (women), (3) > 1-year use of medication for osteoporosis and (4) lack of radiological vertebral assessment for > 1 year. Exclusion criteria were (1) bone metabolic diseases other than osteoporosis, (2) patients with secondary osteoporosis, (3) patients with inability to stand/walk, (4) previous high-energy VFs. All patients performed lateral X-rays of the thoracic and lumbar spine that were evaluated separately both by certified radiologists on site as well as 3 consultant orthopaedic surgeons remotely through a specifically designed web database system. The Genant semi-quantitative method was used for the classification and grading of VFs and statistical analysis of the results was performed. RESULTS: One thousand six hundred fifty-two patients (1516 female, 70.02 ± 8.28 years; 136 male, 74.78 ± 8.25 years) were included in the final analysis. The prevalence of VFs was 25.4%, 76.6% of fractured patients were previously undiagnosed, and of these 39.9% had > 1 VFs. The most common fracture was T12, most fractures were found to be mild (grade 1) across all age groups, and patients 70-79 years and > 80 years were found to have a statistically significantly higher number of fractures than younger patients (p < 0.001). CONCLUSIONS: Our results of the high prevalence of morphometric VFs emphasise the need for baseline assessment of vertebral fragility in patients receiving treatment for osteoporosis, as well as follow-up radiographs at specified time periods while on therapy.

Ethidium bromide MIC screening for enhanced efflux pump gene expression or efflux activity in Staphylococcus aureus.

Multidrug resistance efflux pumps contribute to antimicrobial and biocide resistance in Staphylococcus aureus. The detection of strains capable of efflux is time-consuming and labor-intensive using currently available techniques. A simple and inexpensive method to identify such strains is needed. Ethidium bromide is a substrate for all but one of the characterized S. aureus multidrug-resistant (MDR) efflux pumps (NorC), leading us to examine the utility of simple broth microtiter MIC determinations using this compound in identifying efflux-proficient strains. Quantitative reverse transcription-PCR identified the increased expression of one or more MDR efflux pump genes in 151/309 clinical strains (49%). Ethidium bromide MIC testing was insensitive (48%) but specific (92%) in identifying strains with gene overexpression, but it was highly sensitive (95%) and specific (99%) in identifying strains capable of ethidium efflux. The increased expression of norA with or without other genes was most commonly associated with efflux, and in the majority of cases that efflux was inhibited by reserpine. Ethidium bromide MIC testing is a simple and straightforward method to identify effluxing strains and can provide accurate predictions of efflux prevalence in large strain sets in a short period of time.

Experience gained from the implementation of the fracture liaison service in Greece.

INTRODUCTION: We present the second implementation of a fracture liaison service (FLS) at a national level in Greece. METHODS: This was a multicenter prospective study, organized by the Hellenic Society for the Study of Bone Metabolism, aiming to investigate the tracking and outcome of patients with low-trauma fractures visiting four university orthopedic departments across the country. The primary endpoint was the participation rate of eligible patients with low-trauma fractures in the program within a time frame of 1 year. Secondary outcomes included the percentage of patients initiating osteoporosis treatment, adherence to treatment, and the percentage of patients experiencing subsequent fractures. A major difference with previous reports was the designed implication of the orthopedic surgeon managing the fracture. RESULTS: Among the 1350 eligible patients with major osteoporotic fractures, only 396 (29.3%; mean age 78.1 ± 11.6 years; female/male ratio: 4.4) agreed to participate, nearly all of the latter (n = 392) completing the study. With the exception of seven patients, all participants were receiving anti-osteoporotic treatment at the end of the study. Twelve new fractures were recorded at completion of the 12-month follow-up, which were all sustained in patients who either declined to receive anti-osteoporotic treatment or who discontinued treatment despite advice to the contrary. CONCLUSION: The participation rate remains low and needs improvement. However, we report herein that whenever the treating physician is involved in the FLS structure, patients are more easily convinced to complete the program, to receive anti-osteoporotic treatment, and to stay connected throughout with the outpatient clinic.

The 2018 Guidelines for the diagnosis and treatment of osteoporosis in Greece.

We report the updated guidelines for the management of osteoporosis in Greece, which include guidance on fracture risk assessment, diagnosis-pharmacological treatment-follow-up of osteoporosis based on updated information, and national evidence from Greek clinical practice and the healthcare setting. PURPOSE: The purpose of this report was to update the Guidelines for the Management of Osteoporosis in Greece that was published in 2011. METHODS: In line with the GRADE system, the working group initially defined the main clinical questions that should be addressed when dealing with the diagnosis and management of osteoporosis in clinical practice in Greece. Following a literature review and discussion on the experience gained from the implementation of the 2011 Guidelines transmitted through the national electronic prescription network, the Hellenic Society for the Study of Bone Metabolism (HSSBM) uploaded an initial draft for an open dialogue with the relevant registered medical societies and associations on the electronic platform of the Greek Ministry of Health. After revisions, the Central Health Council approved the final document. RESULTS: The 2018 Guidelines provide comprehensive recommendations on the issues of the timing of fracture risk evaluation and dual-energy X-ray absorptiometry (DXA) measurement, interpretation of the DXA results, the diagnostic work-up for osteoporosis, the timing as well as the suggested medications for osteoporosis treatment, and the follow-up methodology employed during osteoporosis treatment. CONCLUSIONS: These updated guidelines were designed to offer valid guidance on fracture risk assessment, diagnosis-pharmacological treatment-follow-up of osteoporosis based on updated information and national evidence from clinical practice and the healthcare setting. Clinical judgment is essential in the management of every individual patient for the purpose of achieving the optimal outcome in the safest possible way.

The effect of veno-venous ECMO on the pharmacokinetics of Ritonavir, Darunavir, Tenofovir and Lamivudine.

INTRODUCTION: To our knowledge, there is no published data on the pharmacokinetic (PK) profile of antiretroviral (ART) drugs on patients undergoing extracorporeal membrane oxygenation (ECMO) therapy. We present PK analyses of Ritonavir, Darunavir, Lamivudine and Tenofovir in a patient with HIV who required veno-venous ECMO (VV ECMO). METHODS: Plasma concentrations for Ritonavir, Darunavir, Tenofovir and Lamivudine were obtained while the patient was on ECMO following pre-emptive dose adjustments. Published population PK models were used to simulate plasma concentration profiles for the drugs. The population prediction and the observed plasma concentrations were then overlaid with the expected drug profiles using the individual Bayesian post-hoc parameter estimates. RESULTS: Following dose adjustments, the PK profiles of Ritonavir, Darunavir and Tenofovir fell within the expected range and appeared similar to the population prediction, although slightly different for Ritonavir. The observed data for Lamivudine and its PK profile were completely different from the data available in the literature. CONCLUSIONS: To our knowledge, this is the first study reporting the PK profile of ART drugs during ECMO therapy. Based on our results, dose adjustment of ART drugs while on VV ECMO may be advisable. Further study of the PK profile of Lamivudine is required.

Pseudomonas aeruginosa bacteraemia in patients with hematologic malignancies: risk factors, treatment and outcome.

Our aims were to identify factors associated with Pseudomonas aeruginosa (PA) bloodstream infection (BSI) in patients with hematological malignancies and evaluate the outcome of the affected patients. Consecutive patients with hematological malignancies who developed PA BSI were identified. Subsequently, two case-control studies were performed to evaluate the risk factors (i) for PA BSI and (ii) for carbapenem resistant (CR) PA BSI. Patients' outcome was evaluated at 28 days after the onset of bacteraemia. A total of 64 patients with PA BSI (45 caused by CS and 19 by CR organisms) and 128 without PA BSI were enrolled. Patients with rapidly fatal disease, steroid use, neutropenia or prior surgery were more likely to develop PA BSI, whereas patients with previous hospitalization and prior use of fluoroquinolones were more likely to develop CR PA BSI. The 28-day mortality rate was 35.9%. Severity of sepsis was the only independent predictor of adverse outcome.

Docetaxel in combination with irinotecan (CPT-11) in platinum-resistant paclitaxel-pretreated ovarian cancer.

The role of combination chemotherapy regimens in the management of ovarian cancer patients with tumors resistant to platinum compounds has not yet been defined. This multicenter prospective phase II study evaluated the activity and toxicity of the docetaxel-plus-irinotecan combination in ovarian cancer patients whose tumors were resistant to platinum compounds and who had been exposed to paclitaxel. Treatment consisted of docetaxel 60 mg/m2 i.v. followed by irinotecan 200 mg/m2 i.v. both on day 1 followed by prophylactic recombinant human granulocyte-colony stimulating factor (rhG-CSF) support from days 2 to 6, every 3 weeks. Thirty-one patients were enrolled in the study. The median age was 60 years, and the median performance status (ECOG) was 1. Eight (26%) patients had primary tumors resistant to platinum, while the rest of the population had tumor recurrence within 6 months from the last cisplatin treatment. Four chemotherapy cycles per patient were administered, with the delivered dose intensity at 75% of the planned dose for both agents. Among 30 patients evaluable for response, there were 2 (7%) complete and 4 (14%) partial responses (overall response rate 20%; (95% confidence interval, CI, 11%-33%). Stable disease was recorded in 8 (28%) patients and progressive disease in 15 (51%). The median response duration was 4.5 months (range, 3-12), the median time to progression 5 months (range, 2-17) and the median survival 11 months (range, 1-40); the 1-year survival was almost 50%. Myelotoxicity was moderate, with grade 3 and 4 neutropenia occurring in 23% of the patients, grade 3-4 thrombocytopenia in 6% and febrile neutropenia in 13%. Grade 3 diarrhea was observed in 2% of the patients. There was one treatment-related death due to sepsis. In conclusion, the combination of docetaxel plus irinotecan with rhG-CSF support, appears to be a moderately effective regimen with acceptable toxicity for platinum-resistant, paclitaxel-pretreated ovarian cancer patients. Further investigation in comparative studies is required to define the role of combination versus single agent chemotherapy in this group of patients.

Management of gram-positive bacterial infections in patients with cancer.

Bacterial infections, particularly those due to gram-positive bacteria, continue to predominate in patients with cancer. Coagulase-negative and coagulase-positive staphylococci and enterococci remain as common pathogenic microorganisms. Clostridium difficile has emerged as a significant pathogen. Major clinical syndromes include vascular catheter-related infection, febrile neutropenia, diarrhea and colitis. Rising antimicrobial resistance among gram-positive bacteria is of serious concern. The clinical utility of penicillin against streptococci and vancomycin against coagulase-negative and coagulase-positive staphylococci and enterococci may be rapidly diminishing. Liberal empiric use of vancomycin during neutropenic fever needs careful reconsideration. Newer promising anti-gram-positive bacterial drugs with activity against methicillin-resistant staphylococci include daptomycin, linezolid, tigecycline and telavancin. However, toxicity concerns, limited data in immunocompromised populations and high cost prevent the widespread use of these drugs among patients with cancer.

Expression of multidrug resistance efflux pump genes in clinical and environmental isolates of Staphylococcus aureus.

Increased expression of multidrug resistance efflux pump (MDR-EP) genes in clinical isolates of Staphylococcus aureus occurs frequently, but its temporal and geographic variability is unknown. Such strains may contaminate the hospital environment, posing an infection control problem. Nearly 700 clinical isolates from different geographic locales as well as 91 environmental isolates recovered from two Detroit hospitals were studied. Ethidium bromide (EtBr) minimum inhibitory concentration (MIC), quantitative expression of all characterised chromosomal MDR-EP genes, and the presence of qacA/B and smr were determined for all strains. In addition, for norA- and/or mepA-overexpressing strains, the spa type was established. MDR-EP gene overexpression varied temporally and geographically, and overexpressing strains were present in the hospital environment. Increased expression of norA was associated with meticillin resistance and spa type t002, a rare type among control strains, consistent with widespread dissemination of a norA-overexpressing, meticillin-resistant S. aureus (MRSA) clone. Clonal spread also played a role for spa type t008, mepA-overexpressing, meticillin-susceptible strains. An EtBr MIC of ≤12.5 µg/mL was highly specific (>90%) in identifying strains lacking MDR-EP gene overexpression.

Carcinoid tumors of the duodenum and the ampulla of Vater: current diagnostic and therapeutic approach in a series of 8 patients. Case series.

AIM: To describe the specific characteristics of duodenal/perivaterian carcinoids and to analyze the diagnostic/therapeutic approach. MATERIAL AND METHODS: Eight patients were included in our study. Symptoms on admission included dyspepsia, upper gastrointestinal (GI) bleeding and anemia. All patients underwent upper GI endoscopy and gastrointestinal peptides (gastrin) and neuroendocrine markers (Chromogranin-A, CgA) measurement. Imaging studies were performed in all patients, including OCTREOSCAN, while in patients with ACs MRCP or ERCP was also performed, when necessary. Definite diagnosis was confirmed by histopathologic examination. RESULTS: Polypoid masses (carcinoids) were revealed at duodenal bulb and ampulla of Vater, in 5 and 3 patients, respectively. Serum gastrin was moderately increased in 4 patients, while in one patient it was more than 1000 pg/ml. Serum CgA was moderately increased in one patient, in whom OCTREOSCAN detected a solitary hepatic metastasis. Two patients with DC, of less than 1 cm of diameter, were treated by endoscopic polypectomy, while all the other patients underwent surgery. The patient with hepatic metastasis and positive OCTREOSCAN received also Octreotide LAR, resulting in stabilization of disease. No recurrence or metastases were observed during follow-up (range : 1.5-9.6 years). CONCLUSIONS: In DC tumors <1 cm endoscopic excision with close follow-up is an adequate treatment, while in tumors >1 cm and in AC, surgical resection is the treatment of choice. In metastatic tumors, resection of the primary lesion with administration of somatostatin analogues may stabilize the disease and improve patient's quality of life.

Daptomycin: pharmacology and clinical use.

IMPORTANCE OF THE FIELD: Infections caused by Gram-positive organisms have increased in frequency and severity. Daptomycin offers a therapeutic option in an era of increasing resistance. AREAS COVERED IN THIS REVIEW: Literature from 1986 to present was reviewed for pharmacological, preclinical and clinical studies on daptomycin. WHAT THE READER WILL GAIN: The pharmacological properties, resistance mechanisms and clinical applications of daptomycin are discussed. Recommendations are offered on the use of this agent for the treatment of resistant Gram-positive infections. TAKE HOME MESSAGE: Daptomycin is a reliable agent for the treatment of Gram-positive infections. It has been shown to be effective in bacteremia and endocarditis, as well as in soft-tissue infections caused by Gram-positive organisms. Its role in the treatment of bone and joint infections is not well-defined. Resistance is currently uncommon in clinical isolates. However, emergence of resistance during therapy is a concern. This may be prevented by use of higher doses.

In silico genetic correlations of multidrug efflux pump gene expression in Staphylococcus aureus.

Regulatory mechanisms for chromosomal genes encoding multidrug resistance (MDR) efflux pumps (EPs) in Staphylococcus aureus are poorly defined. Microbiological, quantitative gene expression, mRNA half-life and genome data for 11 strains of S. aureus combined with bioinformatic analyses were used to identify correlates of increased MDR EP gene expression. The presence of qacA/B and/or increased expression of one to two MDR EP genes were identified in eight strains. Microbiological and gene expression data correlated in four instances, existing knowledge of the substrate specificity of NorC resulted in correlation in two others, and a transcriptional/translational disconnect is possible for the remaining two. In silico analyses and mRNA half-life determinations linked insertions of nucleotide repeats 3' to the -10 motif of the norA promoter with increased promoter activity. Mutations in the 5'-untranslated and/or coding regions were identified that may affect transcription efficiency. Substitutions of residues in the helix-turn-helix (HTH) motif of NorG may augment its positive regulation of norB. The correlations proposed provide a guide for further experimentation leading to a better understanding of MDR EP gene expression in this important pathogen.