Compact radio emission indicates a structured jet was produced by a binary neutron star merger.

The binary neutron star merger event GW170817 was detected through both electromagnetic radiation and gravitational waves. Its afterglow emission may have been produced by either a narrow relativistic jet or an isotropic outflow. High-spatial-resolution measurements of the source size and displacement can discriminate between these scenarios. We present very-long-baseline interferometry observations, performed 207.4 days after the merger by using a global network of 32 radio telescopes. The apparent source size is constrained to be smaller than 2.5 milli-arc seconds at the 90% confidence level. This excludes the isotropic outflow scenario, which would have produced a larger apparent size, indicating that GW170817 produced a structured relativistic jet. Our rate calculations show that at least 10% of neutron star mergers produce such a jet.

Relevance of multidrug-resistant Pseudomonas aeruginosa infections in cystic fibrosis.

Multidrug-resistant (MDR) Pseudomonas aeruginosa is an important issue for physicians who take care of patients with cystic fibrosis (CF). Here, we review the latest research on how P. aeruginosa infection causes lung function to decline and how several factors contribute to the emergence of antibiotic resistance in P. aeruginosa strains and influence the course of the infection course. However, many aspects of the practical management of patients with CF infected with MDR P. aeruginosa are still to be established. Less is known about the exact role of susceptibility testing in clinical strategies for dealing with resistant infections, and there is an urgent need to find a tool to assist in choosing the best therapeutic strategy for MDR P. aeruginosa infection. One current perception is that the selection of antibiotic therapy according to antibiogram results is an important component of the decision-making process, but other patient factors, such as previous infection history and antibiotic courses, also need to be evaluated. On the basis of the known issues and the best current data on respiratory infections caused by MDR P. aeruginosa, this review provides practical suggestions to optimize the diagnostic and therapeutic management of patients with CF who are infected with these pathogens.

Molecular epidemiology of meticillin-resistant Staphylococcus aureus in Italian cystic fibrosis patients: a national overview.

BACKGROUND: The genetic background, transmissibility and virulence of MRSA have been poorly investigated in the cystic fibrosis (CF) population. The aim of this multicentre study was to analyse MRSA strains isolated from CF patients attending nine Italian CF care centres during a two-year period (2004-2005). All CF patients infected by MRSA were included. METHOD: Antibiotic susceptibility testing, SCCmec typing, Panton-Valentine Leukocidin (PVL) production, and Multi Locus Sequence Typing (MLST) analysis were carried out on collected isolates (one strain per patient). RESULTS: One hundred and seventy-eight strains isolated from 2360 patients attending the participating centres were analysed. We detected 56 (31.4%) SCCmec IV PVL-negative strains, with a resistance rate of 80.3% to clindamycin and of 14.5% to trimethoprim/sulphamethoxazole. MLST analysis showed that many isolates belonged to known epidemic lineages. The largest clone grouping of 29 isolates from 6 centres had the genetic background (ST8-MRSA-IV) of the American lineages USA300 and USA500, thus demonstrating the diffusion of these strains in a population considered at risk for hospital associated infections. CONCLUSIONS: Known MRSA epidemic clones such as USA600, USA800, USA1100, and UK EMRSA-3 were described for the first time in Italy. The diffusion of MRSA strains with high pathogenic potential in the CF population suggests that analysis of the MRSA strains involved in pulmonary infections of these patients is needed.

Relationships between viscoelastic properties of lumbar intervertebral disc and degeneration grade assessed by MRI.

Biomechanical modelling of the spine is of high clinical significance, either for implant evaluation or for surgery planning. Nevertheless, assessment of patient specific material properties still remains an issue, especially the viscoelastic characteristics of lumbar intervertebral discs (IVD). MRI, a dedicated system for IVD examination, provides a signal that is correlated with the biochemical content of the disc. Since IVD composition and its mechanical properties are related, the objectives of this study were to investigate how MRI could inform about viscoelastic properties of lumbar discs, determined from creep experiments. For that purpose, an in vitro protocol was carried out regarding 14 human L1-L2 IVDs; each unfrozen specimen was imaged using MRI and biomechanically tested with 10 min creep under 400 N load. Three-parameter rheologic models were used to fit the experimental curves. Additionally, geometry was obtained and degeneration was assessed using both MRI grading and physical inspection (destructive analysis). Mean creep displacement was 0.19 mm after 10 min. MRI scaling categorized elastic modulus and viscosity of the IVDs in 2 clearly distinct groups without overlaps according to degeneration: mean values for elastic modulus were 12.9 MPa and 5.7 MPa, respectively for mildly and severely degenerated IVDs; mean values for viscosity were 5.7 GPa s and 2.2 GPa s, respectively for mildly and severely degenerated IVDs. Classification derived from physical inspection did not reveal a clear discrimination. MRI could hence provide a quantification of IVDs viscoelastic properties, leading to in vivo direct estimation of material characteristics necessary for patient specific modelling.

Early Pseudomonas aeruginosa infection in individuals with cystic fibrosis: is susceptibility testing justified?

OBJECTIVES: To test the presumption that Pseudomonas aeruginosa isolates responsible for initial lung infection in individuals with cystic fibrosis (CF) are invariably susceptible to antipseudomonal agents. METHODS: Antibiotic susceptibility was determined (MIC and Etest) in two populations of P. aeruginosa associated with initial lung infection. Population 1: environmental isolates (n=78). Population 2: clinical isolates responsible for first infection in previously non-infected patients (85 isolates from 85 patients). Susceptibility or resistance was determined using current BSAC guidelines; ninth version (2009). RESULTS: The majority (≥ 90%) of isolates in both bacterial populations were susceptible to the front-line antipseudomonal agents; colistin, ciprofloxacin, tobramycin, ceftazidime, amikacin and meropenem. Up to 10% of isolates were resistant to one or more antibiotics. A single isolate from each population would be defined as resistant to tobramycin based on a breakpoint (>128 mg/L) that has been suggested for use in patients receiving inhaled therapy. CONCLUSIONS: The high prevalence of susceptibility found in P. aeruginosa isolates associated with initial infection contrasts with the high prevalence of resistance found in isolates from chronic CF lung infection. However, susceptibility in early isolates cannot be presumed. Until further data are obtained from clinically based studies, susceptibility tests should continue to be performed to assist the choice of antibiotics for treatment of early infection.

The costs of treatment of early and chronic Pseudomonas aeruginosa infection in cystic fibrosis patients.

The aim of cystic fibrosis (CF) care is to improve both the life expectancy and quality of life of patients. However, rising costs and limited resources of health services must be taken into account. There are many different antibiotic strategies for therapy of Pseudomonas aeruginosa infection in CF patients. In this 5-year retrospective study we found that the cost of treatment of initial infection is considerably lower than the cost of treating chronic P. aeruginosa infections. The percentage distribution of costs of antibiotic treatment in relationship to the administration route was considerably different between outpatients and inpatients. We observed an increase in antibiotic costs with the age of the patient and the decrease in FEV(1)values. The implementation of early eradication treatment, in addition to decreasing the prevalence of patients chronically infected by P. aeruginosa, might also bring about a notable decrease in costs.

Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis.

Antibiotic strategies against Pseudomonas aeruginosa infection in cystic fibrosis (CF) patients should consider the natural history of the P. aeruginosa infection, ranging from the first isolation of the germ in the airways to isolation at every microbiological culture, and the patient's clinical condition. Antibiotic treatment against P. aeruginosa given at the time of first isolation may prevent or delay chronic infection. The period of intermittent colonization can be considered the time before the development of mucoid P. aeruginosa phenotype. The optimal treatment strategy in this stage remains unclear in terms of agents used and duration of treatment. To treat acute exacerbation, the authors suggest using intravenous administration of two different classes of antibiotics. Maintenance antibiotics are administered to slow the decline in pulmonary function for P. aeruginosa chronic infection. The meaning of maintenance therapy has changed over time, beginning from intravenous quarterly anti-Pseudomonas antibiotics, irrespective of symptoms, to other strategies such as oral macrolides, ciprofloxacin or inhaled antibiotics (tobramycin and colistin). Aerosol delivery can provide a high concentration at the desired site with minimal absorption and therefore low risk of toxicity. There is scientific evidence that antibiotics are clinically effective in CF patients. Antibiotic selection should be based on periodic isolation and identification of pathogens and antimicrobial susceptibility.

Transmission of Burkholderia cepacia complex: evidence for new epidemic clones infecting cystic fibrosis patients in Italy.

To analyze national prevalence, genomovar distribution, and epidemiology of the Burkholderia cepacia complex in Italy, 225 putative B. cepacia complex isolates were obtained from 225 cystic fibrosis (CF) patients attending 18 CF centers. The genomovar status of these isolates was determined by a polyphasic approach, which included whole-cell protein electrophoresis and recA restriction fragment length polymorphism (RFLP) analysis. Two approaches were used to genotype B. cepacia complex isolates: BOX-PCR fingerprinting and pulsed-field gel electrophoresis (PFGE) of genomic macrorestriction fragments. A total of 208 (92%) of 225 isolates belonged to the B. cepacia complex, with Burkholderia cenocepacia as the most prevalent species (61.1%). Clones delineated by PFGE were predominantly linked to a single center; in contrast, BOX-PCR clones were composed of isolates collected either from the same center or from different CF centers and comprised multiple PFGE clusters. Three BOX-PCR clones appeared of special interest. One clone was composed of 17 B. cenocepacia isolates belonging to recA RFLP type H. These isolates were collected from six centers and represented three PFGE clusters. The presence of insertion sequence IS 1363 in all isolates and the comparison with PHDC reference isolates identified this clone as PHDC, an epidemic clone prominent in North American CF patients. The second clone included 22 isolates from eight centers and belonged to recA RFLP type AT. The genomovar status of strains with the latter RFLP type is not known. Most of these isolates belonged to four different PFGE clusters. Finally, a third clone comprised nine B. pyrrocinia isolates belonging to recA RFLP type Se 13. They represented three PFGE clusters and were collected in three CF centers.

Early eradication therapy against Pseudomonas aeruginosa in cystic fibrosis patients.

In cystic fibrosis (CF) patients early antibiotic treatment of lung infection has been shown to lead to Pseudomonas aeruginosa eradication. The present study determined: 1) the time period from eradication to new P. aeruginosa acquisition; 2) P. aeruginosa re-growth and new acquisition; and 3) the impact of eradication therapy on lung function, antimicrobial resistance, emergence of other pathogens and treatment costs. Ciprofloxacin and colistin were used to eradicate P. aeruginosa in 47 CF patients. Bacterial pathogens, lung function decline, P. aeruginosa antimicrobial resistance and anti-pseudomonal serum antibodies were assessed quarterly and compared with an age-matched CF control group. Additionally, costs of antibiotic therapy in both groups were assessed. Early antibiotic therapy leads to a P. aeruginosa free-period of a median (range) of 18 (4-80) months. New acquisition with different P. aeruginosa genotypes occurs in 73% of episodes. It also delays the decline of lung function compared with chronically infected patients, prevents the occurrence of antibiotic resistant P. aeruginosa strains, does not lead to emergence of other pathogens, and significantly reduces treatment costs. The treatment substantially lowers P. aeruginosa prevalence in CF. In conclusion, early antibiotic therapy exerts beneficial effects on the patient's clinical status and is cost-effective compared with conventional antibiotic therapy for chronically infected cystic fibrosis patients.

Sweat testing in newborns positive to neonatal screening for cystic fibrosis.

Sweat chloride concentrations above 40 mmol/l are unusual in newborns screened for cystic fibrosis and should be followed up. Centiles of sweat chloride concentrations in newborns positive to cystic fibrosis neonatal screening are presented. There are no significant correlations between age at sweat testing and sweat chloride concentration or quantity of sweat collected.

Birth weight for gestational age centiles for Italian neonates.

OBJECTIVE: To provide centiles for birth weight (BW) according to gestational age (GA) and sex for infants born in Italy. METHODS: We used records of the whole neonatal population of Tuscany, a region in Italy, from July 1991 to June 2002 as resulting from the database of the cystic fibrosis neonatal screening program (n=290129). We excluded as unlikely for GA those BW that were more than two interquartile ranges above the 75th centile or below the 25th centile for each GA and gender group. RESULTS: We present the 3rd, 10th, 25th, 50th, 75th, 90th and 97th centiles of BW for GA from the 24th to 43rd week of gestation for male and female Italian neonates, as both tables and smoothed curves. CONCLUSIONS: The large size of the examined population allows us to provide up-to-date, reliable BW for GA centiles for Italian newborns, especially for lower GAs.

[Adenocarcinoma of pancreas with situs viscerum inversus totalis]. / Adenocarcinoma del pancreas in situs viscerum inversus totalis.

A case of adenocarcinoma of the head of the pancreas in a patient with situs viscerum inversus totalis, an association described for the third time in literature, is reported. The possible coexistence of malformations of transposed organs and the specular anatomosurgical situation requires particular attention in the diagnosis and preoperative evaluation as well as a careful reorientation of the surgical perspective and a correct surgical conduct.

Antimicrobial susceptibility and synergistic activity of meropenem against Gram-negative non-fermentative bacteria isolated from cystic fibrosis patients.

The objective of the present study was to evaluate the activity of meropenem (a beta-lactam carbapenem with good bactericidal potency and a very wide spectrum of activity) and of ticarcillin, ceftazidime ciprofloxacin, tobramycin, cefepime, which are the most commonly used antimicrobial agents for treatment of pulmonary infections associated with CF. The effect of these antibiotics was tested on 27 multiresistant strains isolated from 24 CF patients during 2000 and 2001. Furthermore, the in vitro synergistic effect of meropenem in association with the other antibiotics was evaluated. Ciprofloxacin, ticarcillin, meropenem and ceftazidime had the most activity and inhibited 66%, 37%, 36% and 33% of strains respectively. The addition of a second antibiotic to meropenem resulted in a synergistic effect on 5 (18.5%) isolates; on average 2.8 synergistic combinations where determined per strain. Of these 27 isolates, antagonism was observed in 3 (11%) strains (1 antagonistic combination per strain). Our study suggests that selecting effective double antibiotic therapy cannot be made empirically for CF patients infected with Gram-negative multiresistant bacilli. Therefore in vitro methods for testing double antibiotic combinations are mandatory.

[Anti-Pseudomonas aeruginosa antibodies, circulating immune complexes, and anticytoplasm antibodies of neutrophils in patients with cystic fibrosis with and without Pseudomonas aeruginosa colonization]. / Anticorpi anti-Pseudomonas aeruginosa, immunocomplessi circolanti ed anticorpi anticitoplasma dei neutrofili in pazienti affetti da fibrosi cistica colonizzati e non da Pseudomonas aeruginosa.

Chronic lung infections, mainly due to Pseudomonas aeruginosa (Pa), account for the most of the morbidity and mortality in CF patients. The pathogenic factors predisposing to airway colonization are still nuclear. Host's immune response is not only poorly protective but can also act as a damaging factor in the development of the disease. Moreover, clinical manifestations of an overactive immune response, including vasculitis and arthropathy, have been recently described in the CF population. To deepen factors involved in the pathogenesis of lung injury, we evaluated the presence of anti-Pa precipitating antibodies, circulating immune complexes (CIC) and antineutrophil cytoplasmic antibodies (ANCA) in sera from 50 CF patients colonized and not by Pa. Number of anti-Pa precipitins was significantly different in chronically and in not colonized patients (p < 0.001; t = 7.75). Anti-Pa antibodies were positively correlated to age (p = 0.002, r = 0.42) and inversely correlated to lung function parameters (p = 0.031 r = -0.35 with respect to FVC). Mean C3-CIC levels in the sera were statistically higher in chronically colonized patients (p = 0.013; t = 2.57); while there was not a significant difference with respect to C1q-CIC values. Four patients, all chronically colonized by Pa, were ANCA-positive at indirect immunofluorescence, showing a cytoplasmic pattern. All 50 patients were found to be negative when tested for anti-mpo and anti-pr3 antibodies with ELISA. In conclusion, our data demonstrate that persistence of Pa provides a stimulus for chronic inflammation and the immune response in CF patients, leading to anti-Pa antibodies and CIC production. Even in the face of further research, we speculate that c-ANCA production is secondary to neutrophil activation with a consequent release of cytoplasmic enzymes that perpetuate and increase the inflammatory process. Since anti-mpo and anti-pr3 antibodies rarely occur in CF patients we suggest that other antigenic specificities may be involved in ANCA production.

Rituximab anti-CD20 monoclonal antibody induces marked but transient reductions of peripheral blood lymphocytes in chronic lymphocytic leukaemia patients.

Rituximab has been recently proposed as an effective non-chemotherapeutic option for patients with follicle centre lymphoma (FCL). However, less is known on its role in chronic lymphocytic leukaemia (CLL). We thus decided to assess its effectiveness on a panel of 7 patients with refractory or relapsed CLL. Mild (5 patients) or severe (1 patient) adverse reactions were observed during the first hours of Rituximab infusion, almost exclusively at the first course. Symptoms rapidly subsided with temporary drug withdrawal and low dose steroids. All patients could receive the whole scheduled treatment. A striking reduction of peripheral blood (PB) lymphocyte counts was observed in all patients (median 93%; range 57-99%). However, Rituximab was poorly effective towards nodal and splenic disease. Patients required additional treatment after a median time of 70 d (range: 20-180 d). Our data show that Rituximab delivery in CLL patients is feasible and has an acceptable toxicity, although it probably does not represent an ideal treatment option when delivered using schedules originally designed for FCL patients. However, responses observed at PB level suggest that Rituximab has an activity which is not negligible and deserves further investigation in CLL. Future approaches will be directed to the development of alternative schedules which may include dose intensification, combination of Rituximab and chemotherapy, and in vivo purging of peripheral blood progenitor cell harvests for autografting procedures.

Direct quantitative transcript analysis of the agr regulon of Staphylococcus aureus during human infection in comparison to the expression profile in vitro.

Bacteria possess a repertoire of distinct regulatory systems promoting survival in disparate environments. Under in vitro conditions it was demonstrated for the human pathogen Staphylococcus aureus that the expression of most virulence factors is coordinated by the global regulator agr. To monitor bacterial gene regulation in the host, we developed a method for direct transcript analysis from clinical specimens. Quantification of specific transcripts was performed by competitive reverse transcription-PCR, and results were normalized against the constitutively expressed gene for gyrase (gyr). Using sputum from cystic fibrosis (CF) patients infected with S. aureus we examined the transcription of the effector molecule RNAIII of agr, of spa (protein A), generally repressed by agr, and of hla (alpha-toxin), generally activated by agr. In the CF lung RNAIII was expressed poorly, indicating an inactive agr in vivo. Despite the low level of RNAIII expression, spa was detectable only in minute amounts and an irregular transcription of hla was observed in all sputum samples. After subculturing of patient strains agr-deficient isolates and isolates with unusual expression profiles, i.e., not consistent with those obtained from prototypic strains, were observed. In conclusion, the agr activity seems to be nonessential in CF, and from the described expression pattern of spa and hla, other regulatory circuits aside from agr are postulated in vivo.

Allergic bronchopulmonary aspergillosis in Italian cystic fibrosis patients: prevalence and percentage of positive tests in the employed diagnostic criteria.

The prevalence of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) patients is difficult to determine because the data in the literature are not homogeneous or comparable. ABPA and CF have similar clinical symptoms which make diagnosis difficult and underestimate the real dimensions of the problem. We conducted an epidemiological study on 3089 Italian CF patients to determine the prevalence of ABPA in Italy and verify the percentage of positive tests in the employed diagnostic criteria. Our results indicate that the prevalence of ABPA in Italian CF patients is 6.18%, mainly in adolescents and young adults. ABPA is diagnosed using clinical symptoms (presence of episodic bronchial obstructions or typical radiographic features) and on the basis of other criteria which can only be partially fulfilled in paediatric patients. Among the diagnostic tests the most sensitive are the total IgE (84.5%), specific IgE anti-Aspergillus fumigatus (81.6%) and the prick test (68.3%). In the absence of clinical symptoms and gold standard diagnostic tests, serological positivity and/or the skin test are not sufficient evidence to confirm the presence of ABPA.