Comparison of multiple definitions for ventilator-associated pneumonia in patients requiring mechanical ventilation for non-pulmonary conditions: preliminary data from PULMIVAP, an Italian multi-centre cohort study.

OBJECTIVES: To compare intensivist-diagnosed ventilator-associated pneumonia (iVAP) with four established definitions, assessing their agreement in detecting new episodes. METHODS: A multi-centric prospective study on pulmonary microbiota was carried out in patients requiring mechanical ventilation (MV). Data collected were used to compare hypothetical VAP onset according to iVAP with the study consensus criteria, the European Centre for Disease Control and Prevention definition, and two versions of the latter adjusted for leukocyte count and fever. RESULTS: In our cohort of 186 adult patients, iVAPs were 36.6% (68/186, 95% confidence interval 30.0-44.0%), with an incidence rate of 4.64/100 patient-MV-days, and median MV-day at diagnosis of 6. Forty-seven percent of patients (87/186) were identified as VAP by at least one criterion, with a median MV-day at diagnosis of 5. Agreement between intensivist judgement (iVAP/no-iVAP) and the criteria was highest for the study consensus criteria (50/87, 57.4%), but still one-third of iVAP were not identified and 9% of patients were identified as VAP contrary to intensivist diagnosis. VAP proportion differed between criteria (25.2-30.1%). CONCLUSIONS: Caution is needed when evaluating studies describing VAP incidence. Pre-agreed criteria and definitions that capture VAP's evolving nature provide greater consistency, but new clinically driven definitions are needed to align surveillance and diagnostic criteria with clinical practice.

Which experimental models and explorations to use in regenerative endodontics? A comprehensive review on standard practices.

Since the discovery of dental pulp stem cells, a lot of teams have expressed an interest in dental pulp regeneration. Many approaches, experimental models and biological explorations have been developed, each including the use of stem cells and scaffolds with the final goal being clinical application in humans. In this review, the authors' objective was to compare the experimental models and strategies used for the development of biomaterials for tissue engineering of dental pulp with stem cells. Electronic queries were conducted on PubMed using the following terms: pulp regeneration, scaffold, stem cells, tissue engineering and biomaterial. The extracted data included the following information: the strategy envisaged, the type of stem cells, the experimental models, the exploration or analysis methods, the cytotoxicity or viability or proliferation cellular tests, the tests of scaffold antibacterial properties and take into account the vascularization of the regenerated dental pulp. From the 71 selected articles, 59% focused on the "cell-transplantation" strategy, 82% used in vitro experimentation, 58% in vivo animal models and only one described an in vivo in situ human clinical study. 87% used dental pulp stem cells. A majority of the studies reported histology (75%) and immunohistochemistry explorations (66%). 73% mentioned the use of cytotoxicity, proliferation or viability tests. 48% took vascularization into account but only 6% studied the antibacterial properties of the scaffolds. This article gives an overview of the methods used to regenerate dental pulp from stem cells and should help researchers create the best development strategies for research in this field.

Prospective evaluation of the aetiology of acute otitis media with spontaneous tympanic membrane perforation.

OBJECTIVES: To evaluate the aetiological role of the main bacterial pathogens associated with acute otitis media (AOM) in children with AOM and spontaneous tympanic membrane perforation (STMP). METHODS: Between 1 May 2015 and 30 April 2016, 177 children, aged 6 months to 7 years, with AOM complicated by STMP within 12 h were prospectively enrolled. Middle ear fluid (MEF) was tested by real-time PCR for Streptococcus pneumoniae, non-typeable Haemophilus influenzae, Streptococcus pyogenes, Moraxella catarrhalis and Staphylococcus aureus. RESULTS: Among the 177 children with AOM and STMP, 92/100 (92.0%) of those with recurrent AOM and 13/77 (16.9%) without recurrent AOM had recurrent STMP (p <0.001). A single pathogen was identified in 70 (39.5%) MEF samples, whereas two, three and four bacteria were detected in 54 (30.5%), 20 (11.3%), and 7 (4.0%) cases, respectively. Non-typeable H. influenzae was the most common and was identified in 90 children (50.8%), followed by M. catarrhalis (62 cases, 35.0%) and S. pneumoniae (48 cases, 27.1%). Non-typeable H. influenzae was the most frequent pathogen in children with co-infections. Children with co-infections, including non-typeable H. influenzae, had significantly more frequent recurrent AOM (adjusted OR 6.609, 95% CI 1.243-39.096, p 0.029). CONCLUSIONS: Recurrent AOM episodes appear to be associated with an increased risk of AOM with STMP. In AOM with STMP, non-typeable H. influenzae is detected at a high frequency, especially in children with recurrent STMP and often in association with other pathogens.

Costs of therapy with biologics in the treatment of moderate to severe plaque psoriasis in the context of the Italian health-care system.

AIM: Biologics were introduced as innovative and effective therapies for the treatment of moderate-to severe psoriasis. However, in the Italian context there are no comparative cost-effectiveness analyses of all biologics currently approved for psoriasis by the European Medicines Agency (EMA). This study estimates whether the cost of ustekinumab (meant as cost of drug therapies and monitoring) is lower, similar to or higher than that of anti-TNF-α. METHODS: The incremental cost-effectiveness ratio (ICER) and the cost-effectiveness ratio (CER) in terms of cost for patients achieving 75% improvement in PASI (PASI 75) were calculated. The analysis, both during the first 52 weeks, including induction and in maintenance period is based on efficacy data taken from single studies. The costs, based on official source, are calculated in the perspective of National Health Service (SSN). RESULTS: Ustekinumab has the lowest cost for responder, resulting always cost-effective and, in some case, cost saving in the baseline scenario at 52 weeks and in maintenance period. CONCLUSION: Ustekinumab seems to be the most favorable biologic in term of cost per PASI 75 responder for the treatment of psoriasis and it is cost-effective in all scenarios analyzed. Further cost-effectiveness evaluations based on data of use of long-term treatment with biologics in clinical practice, are necessary to support this results.

Impact of rhinovirus nasopharyngeal viral load and viremia on severity of respiratory infections in children.

There are few and partially discordant data regarding nasopharyngeal rhinovirus (RV) load and viremia, and none of the published studies evaluated the two variables together. The aim of this study was to provide new information concerning the clinical relevance of determining nasopharyngeal viral load and viremia when characterising RV infection. Nasopharyngeal swabs were obtained from 251 children upon their admission to hospital because of fever and signs and symptoms of acute respiratory infection in order to identify the virus and determine its nasopharyngeal load, and a venous blood sample was taken in order to evaluate viremia. Fifty children (19.9 %) had RV-positive nasopharyngeal swabs, six (12 %) of whom also had RV viremia: RV-C in four cases (66.6 %), and RV-A and RV-B in one case each. The RV nasopharyngeal load was significantly higher in the children with RV viremia (p < 0.001), who also had a higher respiratory rate (p = 0.02), white blood cell counts (p = 0.008) and C-reactive protein levels (p = 0.006), lower blood O2 saturation levels (P = 0.005), and more often required O2 therapy (p = 0.009). The presence of RV viremia is associated with a significantly higher nasopharyngeal viral load and more severe disease, which suggests that a high nasopharyngeal viral load is a prerequisite for viremia, and that viremia is associated with considerable clinical involvement.

Comparison of manual methods of extracting genomic DNA from dried blood spots collected on different cards: implications for clinical practice.

Isolating genomic DNA from blood samples is essential when studying the associations between genetic variants and susceptibility to a given clinical condition, or its severity. This study of three extraction techniques and two types of commercially available cards involved 219 children attending our outpatient pediatric clinic for follow-up laboratory tests after they had been hospitalised. An aliquot of venous blood was drawn into plastic tubes without additives and, after several inversions, 80 microL were put on circles of common paper cards and Whatman FTA-treated cards. Three extraction methods were compared: the Qiagen Investigator, Gensolve, and Masterpure. The best method in terms of final DNA yield was Masterpure, which led to a significantly higher yield regardless of the type of card (p less than 0.001), followed by Qiagen Investigator and Gensolve. Masterpure was also the best in terms of price, seemed to be simple and reliable, and required less hands-on time than other techniques. These conclusions support the use of Masterpure in studies that evaluate the associations between genetic variants and the severity or prevalence of infectious diseases.

Comparison of posterior pharyngeal wall and nasopharyngeal swabbing as a means of detecting the carriage of Neisseria meningitidis in adolescents.

The purpose of this investigation was to evaluate the effectiveness of posterior pharyngeal and nasopharyngeal swabs in identifying and quantifying meningococcal carriage. Two swab samples were obtained from 564 healthy adolescents aged 15-19 years, the first taken from the posterior pharyngeal wall through the mouth and the second through the nose. Bacterial genomic DNA was extracted and screened for Neisseria meningitidis by means of two separate singleplex real-time polymerase chain reactions (real-time PCRs) in order to identify the CtrA and sodC genes. Subsequently, N. meningitidis-positive samples underwent a further singleplex real-time PCR in order to determine the N. meningitidis serogroup, and the DNA was quantified by means of standard curves. Thirty-seven subjects (6.6 %) were found to be carriers of N. meningitidis. The most frequently carried serogroup was serogroup B (15 cases, 40.5 %); serogroups A, Y, X, W135 and Z were found in, respectively, two (5.4 %), five (13.5 %), four (10.8 %), three (8.1 %) and one subject (2.7 %); the serogroup was not identified in seven cases. The detection of carrier status was significantly more frequent using posterior pharyngeal swabs (5.3 % vs. 2.1 %; p = 0.004), which also contained a significantly larger number of N. meningitidis genomic copies (4.91 ± 1.39 vs. 2.50 ± 0.8 log10 genomic copies/mL; p < 0.001). Posterior pharyngeal swabs seem to be better than nasopharyngeal swabs for detecting N. meningitidis carriage in large-scale epidemiological studies because they identify a significantly larger number of pathogen carriers and recover a significantly larger amount of bacterial DNA.

Circulation of different rhinovirus groups among children with lower respiratory tract infection in Kiremba, Burundi.

The purpose of this investigation was to collect information regarding rhinovirus (RV) circulation in children with lower respiratory tract infections (LRTIs) in Burundi, Central Africa. We enrolled all of the children aged between 1 month and 14 years who were admitted to the hospital of Kiremba, North Burundi, with fever and signs and symptoms of LRTI (i.e., cough, tachypnea, dyspnea or respiratory distress, and breathing with grunting or wheezing sounds with rales) between 1 November 2010 and 31 October 2011, and obtained nasopharyngeal swabs for RV detection by means of polymerase chain reaction (PCR). The VP4/VP2 region of the positive samples was sequenced to determine the species of RV (A, B, or C). Four hundred and sixty-two children were enrolled: 160 (34.6 %) with bronchitis, 35 (7.6 %) with infectious wheezing, and 267 (57.8 %) with community-acquired pneumonia (CAP). RV infection was demonstrated in 186 patients [40.3 %; mean age ± standard deviation (SD) 1.77 ± 2.14 years]. RV infection was detected in 78 patients aged <12 months (40.0 %), 102 aged 12-48 months (44.3 %), and six aged >48 months (16.7 %; p < 0.01 vs. the other age groups). The most frequently identified RV was RV-A (81 cases, 43.5 %), followed by RV-C (47, 25.3 %) and RV-B (18, 9.7 %); subtyping was not possible in 40 cases (21.5 %). RV-A was significantly associated with bronchitis and CAP (p < 0.01) and RV-C with wheezing (p < 0.05). In Burundi, RVs are frequently detected in children with LRTIs. RV-A seems to be the most important species and is identified mainly in patients with bronchitis and CAP.

Blunt splenic injury: authors' experience and comparison to literature.

AIM: Splenic injuries, like other blunt traumatic injuries, are very frequent, especially in case of traffic accident. The purpose of this study was to present the authors' experience of blunt splenic trauma and to compare it with the studies described in literature. METHODS: Over a 5-year period 512 injured patients were admitted to the trauma center, 57 of whom presented splenic injuries, and they were retrospectively analyzed. Data review included demographic information, trauma mechanism, admitting hemodinamic parameters, Injury Severity Score. The patients were classified in two groups, one composed by immediate operated injured because their initially hemodinamic instability (27 patients) and another where patients underwent planned nonoperative management (29 patients), which included strict bed rest, frequent physical examinations, serial hematocrits and repeated diagnostic images. The patients were compared to find which factors influence the choice of surgical treatment. RESULTS: There are statistically significant differences between the groups, concerning admitting hemodinamic parameters, as blood pressure and pulse rate, and the grade of anatomic splenic injury. Four patients failed nonsurgical management and required a splenectomy, because during the third day they suddenly presented clinical deterioration. CONCLUSIONS: Comparing these results with literature the authors try to improve spleen preserving program avoiding surgery when possible and using for example splenic embolization.

Isolated ovarian metastasis from a spindle cell malignant melanoma of the choroid 14 years after enucleation: prognostic implication of the keratin immunophenotype.

A 47-year-old woman developed metastatic melanoma to the right ovary 14 years after the enucleation of the right eye for a choroidal spindle cell melanoma. An immunohistochemical study was performed on paraffin sections of both primary and metastatic melanoma specimens to identify markers of both aggressive phenotype and metastatic potential with particular attention to the anomalous expression of cytokeratin intermediate filament proteins. Neoplastic cells of both primary and metastatic tumors immunostained positively for S-100, HMB45, MART-1, and vimentin antibodies, but they were negative for cytokeratins 1-19, 8, 18, and 8,18; <10% of neoplastic cells in both the primary and the metastatic melanomas immunostained for Ki-67 proliferating antigen using MIB-1 antibody. We speculate that the indolent behavior of this ovarian metastasis is reflected by the absence of coexpression of cytokeratins 8 and 18 with vimentin. This case supports the practical value of using this panel of antibodies to evaluate the aggressive potential of uveal melanomas.

Post-operative electrolyte imbalance: its incidence and prognostic implications for elderly orthopaedic patients.

In order to assess incidence and prognostic implications of post-operative electrolyte disorders for elderly patients, 180 patients aged 79.5 +/- 6.8 years, range 70-96 years, admitted to a geriatric-orthopaedic liaison service were prospectively followed from admission to discharge or death. The association of age, basic medical conditions, type of anaesthesia and perioperative complications with post-operative sodium/potassium imbalance and fatality was assessed by logistic regression analysis. The incidence of post-operative electrolyte imbalance and fatality was 15% and 8.8%, respectively. Electrolyte imbalance was independently predicted by spinal anaesthesia [odds ratio (OR) = 2, confidence limits (CL) = 1.24-3.19], multiple pathology (OR = 2, CL = 1.1-3.58), use of cathartics (OR = 1.76, CL = 1.05-2.91) and intra-operative complications (OR = 1.7, CL = 1.03-2.88). Death was predicted by electrolyte imbalance (OR = 2.32, CL = 1.21-4.43), post-operative noninfective complications (OR = 2.3, CL = 1.09-4.84) and age greater than 79 years (OR = 1.17, CL = 1.06-1.3). Post-operative electrolyte imbalance is a marker of very frail medical status and a risk factor for death among elderly orthopaedic patients.

In vitro activity of a new antibacterial drug, trospectomycin sulphate (U-63,366F), against Bacteroides strains isolated from the vagina.

The antibacterial activity of trospectomycin, clindamycin, metronidazole, imipenem, cefoxitin, and piperacillin was tested against 72 Bacteroides spp. strains isolated from the vagina of women with vaginitis by determining the minimal inhibitory concentration using the agar dilution method. Trospectomycin shows a good activity which is comparable to that of imipenem and metronidazole. Its expanded spectrum of activity makes trospectomycin suitable for the use in single-drug therapy of pelvic infections in women.

Predicting mortality and length of stay of geriatric patients in an acute care general hospital.

Three-hundred-eight geriatric patients (mean age = 76.7 yr, range = 70-94 yr) consecutively admitted to an acute care general hospital were followed up to identify the predictors of in-hospital mortality and long stay. Sociodemographic, medical, and functional data were collected within 24 hours from admission and their correlation with the outcomes assessed by logistic regression analysis. The following variables were shown to be independent predictors of death: use of more than 6 drugs (odds ratio = 3.04, confidence limits = 1.05-8.76); abnormal Mini-Mental State score (o.r. = 1.72, c.l. = 1.05-1.83); low ADL score (o.r. = 2.4, c.l. = 1.07-5.56). Extended stay was significantly and independently predicted by polypharmacy (o.r. = 1.94, c.l. = 1.18-3.2) and comorbidity (o.r. = 2.06, c.l. = 1.24-3.38). The mortality rates of patients with cognitive impairment and polypharmacy with or without functional impairment were 40% and 22%, respectively. The proposed method allows identification of high-risk geriatric inpatients by a simple medical and functional assessment on admission.