The burden of severe cases of Influenza disease: the Friuli Venezia Giulia Region experience.

INTRODUCTION: Influenza is a matter of serious concern for clinicians, in both outpatient and in-hospital settings. Worldwide, the 2017-18 epidemic proved to be the most severe since 2003-04. We report a real-world experience regarding the management of patients with influenza admitted to a large teaching hospital in the Friuli Venezia Giulia region during the 2017-2018 influenza season. We also provide a practical guide for the management of hospitalized influenza patients. METHODS: A retrospective observational analysis was conducted among all influenza patients requiring admission to our center during the 2017-18 season. RESULTS: Overall, 29 patients were admitted to the University Hospital of Udine during the 2017-18 season with a diagnosis of influenza. B virus was responsible for the majority of cases. More than 65.5% of the subjects presented with a complication. We estimated that 41.4% of the patients admitted were affected by a "severe form". All these cases required admission to the Intensive Care Unit, with 27.6% and 10.3% needing Orotracheal Intubation and Extracorporeal Membrane Oxygenation, respectively. The fatality rate was 24.1%. Notably, only 9 subjects in our cohort had been vaccinated. Based on the experience acquired during the past season, we propose a practical guide to the management of influenza cases in everyday hospital practice. CONCLUSION: The cornerstones of the management of all hospitalized influenza patients are the rapid identification and treatment of severe forms. Timely and strict adherence to contact and respiratory precautions are also fundamental to reducing the risk of intra-hospital outbreaks. Despite improvements in antiviral therapies and supportive measures, influenza-related morbidity and mortality remain high. In our opinion, a universal vaccination program is the only safe and effective method of filling the gap.

A computerized scoring system to improve assessment of heparin-induced thrombocytopenia risk.

Essentials Current risk scores for heparin-induced thrombocytopenia (HIT) are not computer-friendly. We compared a new computerized risk score with the 4Ts score in a large healthcare system. The computerized risk score agrees with the 4Ts score 85% of the time. The new score could potentially improve HIT diagnosis via incorporation into decision support. SUMMARY: Background (HIT) is an immune-mediated adverse drug event associated with life-threatening thrombotic complications. The 4Ts score is widely used to estimate the risk for HIT and guide diagnostic testing, but it is not easily amenable to computerized clinical decision support (CDS) implementation. Objectives Our main objective was to develop an HIT computerized risk (HIT-CR) scoring system that provides platelet count surveillance for timing and degree of thrombocytopenia to identify those for whom diagnostic testing should be considered. Our secondary objective was to evaluate clinical management and subsequent outcomes in those identified as being at risk for HIT. Methods We retrospectively analyzed data from a stratified sample of 150 inpatients treated with heparin to compare the performance of the HIT-CR scoring system with that of a clinically calculated 4Ts score. We took a 4Ts score of ≥ 4 as the gold standard to determine whether HIT diagnostic testing should be performed. Results The best cutoff point of the HIT-CR score was a score of 3, which yielded 85% raw agreement with the 4Ts score and a kappa of 0.69 (95% confidence interval 0.57-0.81). Ninety per cent of patients with 4Ts score of ≥ 4 failed to undergo conventionally recommended diagnostic testing; 38% of these experienced persistent, unexplained thrombocytopenia, and 4% suffered life-threatening thrombotic complications suggestive of undiagnosed HIT. Conclusion The HIT-CR scoring system is practical for computerized CDS, agrees well with the 4Ts score, and should be prospectively evaluated for its ability to identify patients who should be tested for HIT.

Bone mineral density at femoral neck and lumbar spine in adults with type 1 diabetes: a meta-analysis and review of the literature.

We performed a meta-analysis to evaluate the femoral neck and lumbar spine bone mineral density (BMD) in adults with type 1 diabetes (T1D) compared with controls. Adults with T1D have modestly lower BMD at femoral neck and lumbar spine than adults without diabetes. INTRODUCTION: Fracture risk is four to sixfold higher in adults with T1D. Since BMD is one of the major contributors for fracture risk, we performed a meta-analysis to evaluate differences in femoral neck and lumbar spine BMD between adults with T1D and controls. METHODS: MEDLINE, Ovid, and the Cochrane library and abstracts from various scientific meetings were searched. Studies reporting the femoral neck and/or lumbar spine BMD in adults (age > 20 years) with T1D in comparison with people without diabetes were selected. General linear mixed models were used to assess differences in BMD at femoral neck and lumbar spine between subjects with T1D and controls adjusting for age, sex, and dual x-ray absorptiometry (DXA) instruments. RESULTS: Sixteen studies met the inclusion criteria. The femoral neck BMD was modestly lower in adults with T1D compared to controls (-0.055 g/cm2; 95% CI: -0.065, -0.045). There were no differences in lumbar spine BMD between adults with T1D and controls (0.0062 g/cm2; 95% CI -0.04, 0.016). However, in a sensitivity analysis, lumbar spine BMD was modestly lower in adults with T1D compared to controls (-0.035 g/cm2; -0.049, -0.02). Studies using Lunar DXA instruments have reported higher lumbar spine and femoral neck BMD compared to studies using Hologic DXA instruments. CONCLUSION: Femoral neck and lumbar spine BMD were modestly lower in adults with T1D compared to controls. However, this modest reduction in femoral neck and lumbar spine BMD cannot explain much higher observed fracture risk in adults with T1D.

Clinical effectiveness of a Bayesian algorithm for the diagnosis and management of heparin-induced thrombocytopenia.

Essentials We previously published a diagnostic algorithm for heparin-induced thrombocytopenia (HIT). In this study, we validated the algorithm in an independent large healthcare system. The accuracy was 98%, sensitivity 82% and specificity 99%. The algorithm has potential to improve accuracy and efficiency in the diagnosis of HIT. SUMMARY: Background Heparin-induced thrombocytopenia (HIT) is a life-threatening drug reaction caused by antiplatelet factor 4/heparin (anti-PF4/H) antibodies. Commercial tests to detect these antibodies have suboptimal operating characteristics. We previously developed a diagnostic algorithm for HIT that incorporated 'four Ts' (4Ts) scoring and a stratified interpretation of an anti-PF4/H enzyme-linked immunosorbent assay (ELISA) and yielded a discriminant accuracy of 0.97 (95% confidence interval [CI], 0.93-1.00). Objectives The purpose of this study was to validate the algorithm in an independent patient population and quantitate effects that algorithm adherence could have on clinical care. Methods A retrospective cohort comprised patients who had undergone anti-PF4/H ELISA and serotonin release assay (SRA) testing in our healthcare system from 2010 to 2014. We determined the algorithm recommendation for each patient, compared recommendations with the clinical care received, and enumerated consequences of discrepancies. Operating characteristics were calculated for algorithm recommendations using SRA as the reference standard. Results Analysis was performed on 181 patients, 10 of whom were ruled in for HIT. The algorithm accurately stratified 98% of patients (95% CI, 95-99%), ruling out HIT in 158, ruling in HIT in 10 and recommending an SRA in 13 patients. Algorithm adherence would have obviated 165 SRAs and prevented 30 courses of unnecessary antithrombotic therapy for HIT. Diagnostic sensitivity was 0.82 (95% CI, 0.48-0.98), specificity 0.99 (95% CI, 0.97-1.00), PPV 0.90 (95% CI, 0.56-0.99) and NPV 0.99 (95% CI, 0.96-1.00). Conclusions An algorithm incorporating 4Ts scoring and a stratified interpretation of the anti-PF4/H ELISA has good operating characteristics and the potential to improve management of suspected HIT patients.

Impact of pneumococcal conjugate vaccination: a retrospective study of hospitalization for pneumonia in North-East Italy.

INTRODUCTION: Pneumonia remains a common reason for hospitalizing infants and the elderly worldwide, and streptococcal infection is often responsible. The aim of this study was to assess the burden of pneumonia in a large general population. METHODS: All pneumonia-related hospitalizations from 2004 to 2013 in north-east Italy were identified from the hospital records with a first-listed diagnosis on discharge of bacterial pneumonia, or a first-listed diagnosis on discharge of meningitis, septicemia or empyema associated with a secondary diagnosis of bacterial pneumonia. We identified major comorbidities, calculated agespecific case-fatality rates (CFR), and estimated the related cost to the health care system. RESULTS: Of the 125,722 hospitalizations identified, 96.9% were cases of pneumonia, 2.4% of septicemia, 0.4% of meningitis, and 0.3% of empyema; 75.3% of hospitalizations involved ≥ 65-yearolds. The overall CFR was 12.4%, and it increased with age, peaking in people over 80 (19.6%). The mean annual pneumonia-associated hospitalization rate was 204.6 per 100,000 population, and it peaked in 0- to 4-year-old children (325.6 per 100,000 in males, 288.9 per 100,000 in females), and adults over 65 (844.9 per 100,000 in males, 605.7 per 100,000 in females). Hospitalization rates dropped over the years for the 0-4 year-olds, and rose for people over 80. The estimated overall annual cost of these pneumonia-related hospitalizations was approximately € 41 million. CONCLUSIONS: This study shows that the burden on resources for pneumonia-related hospitalization is an important public health issue. Prevention remains the most valuable tool for containing pneumonia, and vaccination strategies can help in the primary prevention of infection, possibly reducing the number of cases in all age groups.

Epidemiological and molecular assessment of a measles outbreak in a highly vaccinated population of northeast Italy.

Two distinct measles outbreaks, unrelated from the epidemiological point of view but caused by genetically related strains, occurred in the Friuli Venezia Giulia region of northeastern Italy. Forty-two cases were reported during the period April-May 2008. In the first outbreak the index case was a teacher who introduced the virus into the Pordenone area, involving eight adolescents and young adults. The other concomitant outbreak occurred in the city of Trieste with 33 cases. The containment of the epidemics can be explained by the high MMR vaccine coverage in an area where the first dose was delivered to 93·4% and the second dose to 88·3% of the target children. Phylogenetic analysis of 14 measles virus strains showed that they belonged to a unique D4 genotype indistinguishable from the MVs/Enfield.GBR/14.07 strain, probably introduced from areas (i.e. Piedmont and Germany) where this genotype was present or had recently caused a large epidemic.

Cephalometric evaluation of white Brazilian adult skeleton.

AIM: The aim of the present study was to compare cephalometric norms of white Brazilian adults with the values described by Tweed, who measured white North American adults. Sexual dimorphism was also evaluated, and male and female facial features were compared. METHODS: Samples were obtained from 40 lateral cephalograms and divided into groups of 20, according to patient's gender. The radiographs were analyzed using the computer-assisted Tweed cephalometric analysis and the 2.0 Radiocef software. Results were analyzed statistically using the Student's t test for genders and ethnicities. The level of significance was set at P< or =0.05. RESULTS: The comparison with Tweed norms revealed that Brazilians have a convex profile and more marked labial tipping of mandibular incisors than North Americans. Sexual dimorphism was found only in linear measurements, which suggests that facial morphology is similar for Brazilian males and females. CONCLUSIONS: Results revealed significant statistical differences in linear and angular cephalometric dimensions between different ethnic groups, which supports the idea that ethnicity should be included in cephalometric analyses.

Emergence of fox rabies in north-eastern Italy.

Italy has been classified as rabies-free since 1997. In October 2008, two foxes have been diagnosed with rabies in the Province of Udine, north-east Italy. One case of human exposure caused by a bite from one of the foxes has occurred and was properly treated.

CT colonography: Project of High National Interest No. 2005062137 of the Italian Ministry of Education, University and Research (MIUR).

PURPOSE: The aim of this paper is to describe the Web site of the Italian Project on CT Colonography (Research Project of High National Interest, PRIN No. 2005062137) and present the prototype of the online database. MATERIALS AND METHODS: The Web site was created with Microsoft Office Publisher 2003 software, which allows the realisation of multiple Web pages linked through a main menu located on the home page. The Web site contains a database of computed tomography (CT) colonography studies in the Digital Imaging and Communications in Medicine (DICOM) standard, all acquired with multidetector-row CT according to the parameters defined by the European Society of Abdominal and Gastrointestinal Radiology (ESGAR). The cases present different bowel-cleansing and tagging methods, and each case has been anonymised and classified according to the Colonography Reporting and Data System (C-RADS). RESULTS: The Web site is available at http address www.ctcolonography.org and is composed of eight pages. Download times for a 294-Mbyte file were 33 min from a residential ADSL (6 Mbit/s) network, 200 s from a local university network (100 Mbit/s) and 2 h and 50 min from a remote academic site in the USA. The Web site received 256 accesses in the 22 days since it went online. CONCLUSIONS: The Web site is an immediate and up-to-date tool for publicising the activity of the research project and a valuable learning resource for CT colonography.

Value of endorectal MRI and MRS in patients with elevated prostate-specific antigen levels and previous negative biopsies to localize peripheral zone tumours.

AIM: To evaluate prospectively the role of endorectal magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) in detecting peripheral zone tumour in patients with total prostate-specific antigen (PSA) values>or=4 ng/ml and one or more negative transrectal ultrasound (TRUS) biopsy rounds. MATERIAL AND METHODS: Fifty-four consecutive men (mean age 65.4+/-5.2 years, mean total PSA 10.8+/-7.5 ng/ml), underwent a combined MRI-MRS examination with endorectal coil. MRI included transverse, coronal, and sagittal T2-weighted and transverse T1-weighted fast spin-echo sequences. MRS data were acquired using a double spin-echo point resolved spectroscopy (PRESS) sequence. A 10-site scheme was adopted to evaluate the prostate peripheral zone. A peripheral prostatic site was classified as suspicious if low intensity signal was present on T2-weighted images and/or if the choline+creatine/citrate ratio was >0.86. Following MRI-MRS all patients were submitted to a standard 10-core biopsy scheme to which from one to three supplementary samples were added from suspicious MRI and/or MRS sites. In per-patient analysis findings were considered true-positive if biopsy positive patients were classified as suspicious, irrespectively of lesion site indication. RESULTS: Prostate cancer (PC) was detected in 17 of 54 patients (31.5%); median Gleason score was 6 (range 4-8). On a per-patient basis sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were respectively 100, 64.9, 56.7, 100, and 75.9% for MRI; 82.2, 70.3, 57.7, 92.9, and 75.9% for MRS; and 100, 51.4, 48.6, 100, and 66.7% for combined MRI-MRS. In all the 17 PC patients, combined MRI-MRS correctly indicated the sites harbouring cancer, whereas both MRI and MRS gave erroneous indications in two patients. CONCLUSION: The results of the present study show that MRI alone might be able to select negative patients in whom further biopsies are unnecessary. The combination of MRI and MRS might be able to drive biopsies in suspicious sites and increase the cancer detection rate. Further studies are required to confirm these data.

Diagnostic accuracy of portal-phase CT and MRI with mangafodipir trisodium in detecting liver metastases from colorectal carcinoma.

AIM: To compare the diagnostic accuracy of single section spiral computed tomography (CT) and magnetic resonance imaging (MRI) with tissue-specific contrast agent mangafodipir trisodium (MnDPDP) in the detection of colorectal liver metastases. MATERIAL AND METHODS: One hundred and twenty-five consecutive patients undergoing surgery for primary and/or metastatic disease were evaluated using CT (5 mm collimation and reconstruction interval, pitch 2), two-dimensional fast spoiled gradient echo (2D FSPGR) T1 and single shot fast-spin echo (SSFSE) T2 weighted breath-hold MRI sequences, performed before and after intravenous administration of MnDPDP. The reference standards were intraoperative ultrasound and histology. RESULTS: The per-patient accuracy of CT was 72.8 versus 78.4% for unenhanced MRI (p = 0.071) and 82.4% for MnDPDP-enhanced MRI (p = 0.005). MnDPDP-enhanced MRI appeared to be more accurate than unenhanced MRI but this was not significant (p = 0.059). The sensitivity of CT was 48.4% versus 58.1% for unenhanced MRI (p = 0.083) and 66.1% for MnDPDP-enhanced MRI (p = 0.004). The difference in specificity between procedures was not significant. The per-lesion sensitivity was 71.7, 74.9 and 82.7% for CT, unenhanced MRI, and MnDPDP-enhanced MRI, respectively; the positive predictive value of the procedures was respectively 84.0, 96.0 and 95.8%. MnDPDP-enhanced MRI provided a high level diagnostic confidence in 92.5% of the cases versus 82.5% for both unenhanced MRI and CT. The kappa value for inter-observer variability was >0.75 for all procedures. CONCLUSIONS: The diagnostic accuracy and sensitivity of MnDPDP-enhanced MRI is significantly higher than single section spiral CT in the detection of colorectal cancer liver metastases; no significant difference in diagnostic accuracy was observed between unenhanced MRI and MnDPDP-enhanced MRI.

CT colonography: screening in individuals at high risk for colorectal cancer.

The use of computed tomographic colonography (CTC) as a screening test for colorectal cancer is being advocated with growing enthusiasm by physicians and the public as stronger evidence of its validity and limited invasiveness emerges from the literature. Because the approach to surveillance of colorectal cancer depends on an individual's degree of risk category, which depends on familial and personal histories, it seems logical that the diagnostic performance and cost efficacy of screening CTC may differ according to the characteristics of the target population. Although CTC seems a valid option in low- to average-risk populations, pending a careful assessment of its cost and estimates of its cost efficacy, there are some important issues that should be addressed when it comes to considering its use in high-risk patients. The expected larger number of induced colonoscopies and higher false-positive rates are likely to have a great influence on CTC costs, but if its implementation causes a dramatic increase in the number of patients willing to undergo screening, thanks to its acceptability, then the cost efficacy ratio may ultimately become competitive with all other screening strategies for colorectal cancer. We strongly feel that large and well-conducted trials are needed to clarify the role of CTC in screening patients at increased risk of developing colorectal cancer.

Evidence of increased clinical protection of an MF59-adjuvant influenza vaccine compared to a non-adjuvant vaccine among elderly residents of long-term care facilities in Italy.

We evaluated whether the increased immunogenicity provided by an MF59-adjuvant influenza vaccine translates into increased protection among the elderly. Residents of 25 long-term care facilities received either the adjuvant or a non-adjuvant vaccine. The odds ratios (OR) of influenza-like illness were calculated for non-adjuvant vs. adjuvant vaccine recipients, also stratifying for chronic cardiovascular, respiratory, and renal diseases. The risk was higher for the non-adjuvant vaccine recipients and highest for those with respiratory disease (OR 2.27, 95% CI 1.09-4.82) and cardiovascular disease (OR 1.88; 95% CI 1.31-2.72). In this study the MF59-adjuvant vaccine provided superior clinical protection among the elderly, especially those with chronic diseases.

Ileocecal valve imaging on computed tomographic colonography.

BACKGROUND: The aim of our study was to describe the visualization, normal anatomy, and variations of the ileocecal valve with computed tomographic (CT) colonography to provide information about its optimal imaging. METHODS: We analyzed data in two- and three-dimensional rendering mode in 71 consecutive patients who underwent routine CT colonoscopy followed by conventional colonoscopy for confirmation of the radiologic findings. RESULTS: Complete visualization of the ileocecal valve was better achieved in the supine than in the prone position (82% vs. 62%, respectively); the ileocecal valve appeared in 64% of cases in the supine position when it was invisible in prone position (p < 0.0001). Partial visualization of the ileocecal valve was possible in 94% of cases. The ileocecal valve was of labial type in 76%, papillary type in 21%, and lipomatous in 3% of cases. The orifice was identified in 53% of ileocecal valves; in two cases of cecal carcinoma, the normal ileocecal valve morphology was grossly disrupted. CONCLUSION: The ileocecal valve was at least partly visualized by CT colonoscopy in 94% of cases, more frequently in the supine position. Its most common normal morphology is the labial type. The absence of orifice visualization alone is not a specific sign for neoplasia, but its presence helps distinguish physiologic bulging from neoplasia.

C-C versus C-O anionic domino cycloalkylation of stabilized carbanions: facile one-pot stereoselective preparation of functionalized bridged bicycloalkanones and cyclic enol ethers.

alpha,alpha'-Diactivated cyclic- or acyclic ketones undergo a chemoselective base promoted (K2CO3, DBU) one-pot C-C cycloalkylation, with 1,3- and 1,4-dihalides having a cis-like fixed configuration. This reaction gives highly functionalized bicyclo[3.2.1]octan-9-one and bicyclo[4.2.1]nonan-9-one derivatives, which are easily transformed to seven- and eight-membered rings through a high yield retro-Dieckmann cleavage. Starting from trans-1,4-dibromo-2-butenes, the transformation is governed by stereoelectronic factors and leads, through a chemo- and stereoselective C-O cycloalkylation, to synthetically valuable monocyclic or fused polycyclic functionalized enol ethers of high synthetic value. Semiempirical calculations showed a small difference in energy and the late character of the transition states leading to cis and trans isomers of the corresponding fused polycyclic enol ethers. These results, although minimizing the influence of a destabilizing 1,3-interaction on the outcome of the reaction, are qualitatively in agreement with the experimental results.

[Use of virtual endoscopy with computerized tomography in the identification of colorectal neoplasms. Prospective study with symptomatic patients]. / Impiego dell'endoscopia virtuale con Tomografia Computerizzata nell'identificazione delle neoplasie colorettali. Studio prospettico in pazienti sintomatici.

INTRODUCTION: Aim of this study was to evaluate the sensitivity of virtual colonoscopy (CT colonography) in the identification of colorectal cancer and to define the limitations and the advantages of this imaging modality, as well as indications to the examination. MATERIAL AND METHODS: We examined prospectively 62 symptomatic patients aged 36 to 82 years (28 women and 34 men). All patients underwent both conventional and virtual colonoscopy on the same day; the conventional examination allowed exploration of the entire colon. RESULTS: Conventional colonoscopy identified 89 lesions 3-50 mm in diameter, namely 84 benign and 5 malignant lesions. No lesions were identified in 12 patients. CT colonography identified 52 of the 89 lesions, with 57.1% diagnostic accuracy. There were 11 false positives (82.5% positive predictive value and 52.2% specificity) and 37 false negatives (24.5% negative predictive value and 58.4% sensitivity). Sensitivity was significantly higher (85.7%) for polyps > or = 1 cm. CONCLUSIONS: Virtual colonoscopy is an imaging modality with good diagnostic yield, well tolerated by patients and with great potentials for further development. We suggest that the examination be performed in symptomatic patients who cannot undergo total colonoscopy or refuse the other imaging modalities. Further studies are warranted in larger series of patients, possibly introducing it in screening programs.

HIV-1 transmission in injection paraphernalia: heating drug solutions may inactivate HIV-1.

In response to recent concerns about risk of HIV-1 transmission from drug injection paraphernalia such as cookers, ethnographic methods were used to develop a descriptive typology of the paraphernalia and practices used to prepare and inject illegal drugs. Observational data were then applied in laboratory studies in which a quantitative HIV-1 microculture assay was used to measure the recovery of infectious HIV-1 in cookers. HIV-1 survival inside cookers was a function of the temperature achieved during preparation of drug solutions; HIV-1 was inactivated once temperature exceeded, on average, 65 degrees C. Although different types of cookers, volumes, and heat sources affected survival times, heating cookers 15 seconds or longer reduced viable HIV-1 below detectable levels.