In vivo development of daptomycin resistance in vancomycin-susceptible methicillin-resistant Staphylococcus aureus severe infections previously treated with glycopeptides.

Our aim was to describe the clinical and microbiological features of four cases of severe vancomycin-susceptible methicillin-resistant Staphylococcus aureus (MRSA) infections in which the vancomycin non-susceptibility development and daptomycin resistance occurred under therapy with teicoplanin (three cases) and daptomycin switched to vancomycin (one case). Clinical data were retrospectively reviewed. On nine clinical epidemiologically unrelated daptomycin-susceptible (DAP-S) and daptomycin-resistant (DAP-R) MRSA, we performed: (i) DAP-VAN-TEC-CFX-RIF minimum inhibitory concentrations (MICs); (ii) glycopeptide resistance detection (GRD) by δ-hemolysis; (iii) glycopeptide population analysis; (iv) molecular characterization by PFGE-MLST-SCCmec-agr-typing; (v) rpoB and mprF single nucleotide polymorphisms (SNPs); (vi) dltA-mprF-atl-sceD expression by real-time quantitative polymerase chain reaction (qPCR). Three out of the four patients did not survive despite salvage treatment; two died with active MRSA infection and one died because of Stenotrophomonas maltophilia sepsis. The fourth patient, in which a reversion to a DAP-S phenotype occurred, survived with daptomycin plus trimethoprim/sulfamethoxazole and oxacillin treatment, and endovascular device removal. Daptomycin resistance development was preceded by a stable heterogeneous vancomycin-intermediate S. aureus (hVISA) or VISA phenotype acquisition, while in one case, daptomycin resistance was preceded by an unstable daptomycin heteroresistance (hDAP) behavior reverting to DAP-S during vancomycin plus rifampin therapy followed by high doses of daptomycin. All DAP-R strains showed hVISA or DAP-R traits, including mutations and/or up-regulation of genes involved in cell wall turnover and cell membrane perturbation. In our study, daptomycin resistance arose during glycopeptide therapy. The emergence of DAP-R isolates was preceded by a stable VISA or hVISA phenotype or by instability reverting to a DAP-S heteroresistant phenotype. Daptomycin, as first-line therapy for the treatment of severe MRSA infections, should be used at optimal dosage combined with other agents such as beta-lactams, to prevent daptomycin resistance occurrence.

Current options to surgical treatment in osteoporotic fractures.

Treatment of osteoporotic fractures leads to significant challenges for the surgeon, including poor implant fixation related to low bone quality and compromised capacity of fracture healing. This article reviews the osteosynthesis and arthroplasty results in the surgical treatment of proximal femur, proximal humerus and wrist fractures to define the current options to decrease failure in fragility fracture management.

Isolation of NDM-1-producing Pseudomonas aeruginosa sequence type ST235 from a stem cell transplant patient in Italy, May 2013.

We describe the first isolation of an NDM-1-producing Pseudomonas aeruginosa in Italy. In May 2013, a patient with acute lymphoblastic leukaemia and history of prior hospitalisation in Belgrad, Serbia, underwent stem cell transplantation at a tertiary care hospital in Rome, Italy. After transplantion, sepsis by NDM-1-producing P. aeruginosa occurred, leading to septic shock and fatal outcome.

Multiple bilateral pulmonary "fungus balls" in an immunocompetent patient unsuitable for surgical treatment: efficacy of azoles treatment.

Data guiding management of pulmonary mycetomas are based on uncontrolled trials and case reports. Surgical resection represents a definitive treatment associated with high mortality and sometimes not feasible due to clinical conditions. We report a case of an immunocompetent patient with multiple pulmonary mycetomas, suggestive for probable chronic aspergillosis, in which surgery was contraindicated. The patient experienced a good response to long-term oral voriconazole therapy with remarkable clinical and radiological improvement at three-month follow-up. In cases of probable chronic aspergillomas, when surgery is contraindicated, long-term antifungal therapy with voriconazole seems to be a valid alternative option.

An expanded series of distal bypass using the distal vein patch technique to improve prosthetic graft performance in critical limb ischemia.

OBJECTIVES: The endovascular first approach has led to increasing complexity for surgical bypass especially in those patients without autogenous conduit. The use of vein interposed at the distal anastomosis has been reported to improve the results of prosthetic grafts. This series expands our initial experience with the distal vein patch technique (DVP) reporting a larger cohort with enhanced follow-up. DESIGN: A retrospective review of prospectively collected data was performed for distal bypasses from July 1995 to November 2008. MATERIALS/METHODS: 1296 tibial bypasses were performed with 270 using the DVP technique. Patient demographics included; 49% diabetes, 20% chronic renal failure, 33% prior failed bypass. Indications for revascularization were claudication (9.3%), rest pain (27.8%), gangrene (22.2%), and non-healing ulceration (40.7%). Lack of vein for the bypass conduit resulted from previous failed grafts (55%), coronary bypass (18%), poor quality vein (23%), or prior vein stripping (8%). Follow-up ranged from 1 to 48 months with graft surveillance by pulse exam, ABI, and Duplex ultrasound. Primary patency and limb salvage ± SE were determined by Kaplan-Meier life-table analysis using Rutherford criteria. RESULTS: Bypasses originated from the external iliac (29%), CFA (55%), SFA (13%), popliteal (1%), and prior grafts (2%). Recipient arteries were below knee popliteal (6%), anterior tibial (25%), posterior tibial (30%), and peroneal (39%). Perioperative graft failure occurred in 13 cases with a total of 41 graft failures leading to 39 major amputations. Primary graft patency from one to four years was 79.8%, 75.6% 65.9%, and 51.2%. Corresponding limb salvage rates were 80.6%, 78.0%, 75.7%, and 67.5%. CONCLUSION: Although not addressed by a randomized trial, we believe this expanded series is a more accurate reflection of expected results confirming that the DVP bypass leads to reasonable long-term results for those challenging patients that require prosthetic distal bypass for lower extremity revascularization.

Accurate quantitative determination of the total amounts of Strecker aldehydes contained in wine. Assessment of their presence in table wines.

Strecker aldehydes (SAs) are key determinants of wine shelf-life and can be present in unoxidized wines in odorless forms, such as hydroxyalkylsulfonates, imines or acetals. A robust and accurate method for the determination of total forms of SAs, based on the classical derivatization with O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine (PFBHA) and in the selective solid phase extraction of derivatives has been optimized and validated. Matrix effects have been solved by the use of adequate internal standards and by large-enough equilibration times under anoxic conditions. Method figures of merit are highly satisfactory in terms of detection limits (<0.1 µg/L), linearity (R2 > 0.997), reproducibility (5-13%) and recoveries (RSDs, between 2 and 10%, for 3-methylbutanal, 14%). The analysis of total SAs in 108 Spanish wines revealed that between 52% and 70% of unoxidized red wines and likely a similar fraction of white wines, contain levels of SAs high enough to cause oxidative aromas if bound forms of SAs cleave.

Acute limb ischemia due to ONYX 34 migration during embolization of a traumatic pseudoaneurysm of the superficial femoral artery.

Pseudo-aneurysms of the arteries of the lower limbs are a possible complication of leg trauma. Complications include rupture, infection, pain and distal embolization. This is a case of a 24-year-old man hospitalized after a car accident, in which we discovered a 1-cm large pseudo-aneurysm of the right superficial femoral artery. The pseudo-aneurysm in first place was treated by the interventional-radiologist for an endovascular repair by embolization with ONYX 34, but during the procedure the copolymer embolized in the arterial axe with complete obstruction of blood-flow in the lower limb. An urgent open surgical revascularization was then attempted by our team with the result of complete patency of the femoro-popliteal axis and of the tibial vessels. Embolization with ONYX is an effective and safe method, but it is susceptible to this type of complication for larger pseudo-aneurysms, where it is required an introduction of a larger quantity of polymer.

Is antegrade nailing a proper option in 2- and 3-part proximal humeral fractures?

PURPOSE: To report our experience with antegrade short locked intramedullary nail for treatment of proximal humeral fractures and to review the current literature. MATERIALS AND METHODS: From January 2012 to July 2013, 41 patients affected by two and three-part proximal humeral fractures were treated with surgical internal fixation with short locked intramedullary nails. Outcome analysis included standard clinical follow-up, Constant shoulder score and plain radiographs. The mean follow-up was 30 months (range 24-42). Moreover, a review of the literature was carried out. RESULTS: The mean Constant shoulder score was 81.5, excellent functional outcomes in 24/38 patients. All the fractures healed in an average time of 3.7 months. Five patients underwent additional operations, complications included hardware penetration into the joint (n = 2), backed out screw (n = 1), shoulder impingement due to protrusion of the nail (n = 2) and superficial infection (n = 1). The literature review showed 530 patients affected by proximal humeral fracture and treated with intramedullary nail with mean age of 65 years, mean follow-up of 22.2 months and a Constant shoulder score of 72.9 points; the major complications reported were backing out of the screws, shoulder impingement and joint protrusion of the screws. CONCLUSIONS: Antegrade short locked intramedullary nail allows stable fixation, minimal soft tissue dissection, early mobilization of the shoulder and good outcomes. It is an efficacious therapeutic solution for 2- and 3-part proximal humeral fractures.

The role of procalcitonin outside of the Intensive Care Unit (ICU): a multidisciplinary approach.

OBJECTIVE: Biochemical markers are commonly used in medicine to guide diagnostic investigation or therapy duration and/or monitor treatment efficacy. Due to the emergence and spread of antimicrobial resistance, markers able to prompt a more rational use of antimicrobial therapy are regarded with the greatest attention. Procalcitonin (PCT) certainly stands out among others, yet its role must be better established especially outside of the critical care area. Data about PCT utilization in non-critical patients, optimal negativity cut-offs as well as a protocol for measurement timing are all lacking. MATERIALS AND METHODS: To address these issues, a focus group was set up to propose and endorse shared statements regarding the most beneficial use of PCT in real life as infection marker for non-critical patients, based on the authors' experience and a review of recent literature. RESULTS: A group of nine experts in the fields of Infectious Diseases, Internal Medicine, Microbiology, Clinical Chemistry, Surgery and Medical Economics participated in the discussion of nine pre-specified statements. CONCLUSIONS: The potential role for PCT in differentiating infectious and non-infectious clinical syndromes and guiding antimicrobial therapy discontinuation was acknowledged. Moreover, a shared measurement protocol and desirable cut-offs for the non-critical area were proposed. Finally, observations were made about a reasonable selection of the patient population to be tested.

Suicidal jumper's fracture - sacral fractures and spinopelvic instability: a case series.

BACKGROUND: Sacral fractures with spinopelvic dissociation are rare, and hard to diagnose and treat. Fractures with a H- or U-shaped line are severely unstable, due to a dissociation of the spine and of the upper body of the sacrum from the pelvis. They are commonly due to high-energy trauma events, with severe neurological injuries in 80% of cases. CASES PRESENTATION: Five polytraumatized Caucasian patients, three women and two men (mean age: 34 years old) with spinopelvic dissociation were selected. All patients underwent level I-II examinations with radiographs and computed tomography total-body scans; all patients needed damage-control procedures. Sacral fractures were classified according to Denis and Roy-Camille classifications, and neurologic injuries of cauda equina according to Gibbons classification. Patients' outcome was analyzed with the Majeed score. Definitive surgical treatment was appropriate for two patients (lumbar-pelvic fixation or transverse bar). Clinical and radiographic outcomes were analyzed periodically. Four patients survived, all of them suffered severe neurologic deficits. One case of osteomyelitis was treated with the removal of the fixation implants 23 months after the accident. CONCLUSIONS: Diagnosis of spinopelvic dissociation is frequently overlooked due to the severe associated injuries affecting these patients. In cases of a fall from high height, this lesion should be investigated with a lateral sacral radiographic view and computed tomography scan of the pelvis. If untreated, it can lead to severe and progressive neurologic deficit with muskuloskeletal deformities and persistent pain. Early decompression treatment is controversial, but an early lumbopelvic fixation is recommended. A correct diagnosis and early treatment can reduce morbidity and strongly improve the outcome of these patients.

The cosmic ray shadow of the Moon observed with the ANTARES neutrino telescope.

One of the main objectives of the ANTARES telescope is the search for point-like neutrino sources. Both the pointing accuracy and the angular resolution of the detector are important in this context and a reliable way to evaluate this performance is needed. In order to measure the pointing accuracy of the detector, one possibility is to study the shadow of the Moon, i.e. the deficit of the atmospheric muon flux from the direction of the Moon induced by the absorption of cosmic rays. Analysing the data taken between 2007 and 2016, the Moon shadow is observed with 3.5 σ statistical significance. The detector angular resolution for downward-going muons is 0 . 73 ∘ ± 0 . 14 ∘ . The resulting pointing performance is consistent with the expectations. An independent check of the telescope pointing accuracy is realised with the data collected by a shower array detector onboard of a ship temporarily moving around the ANTARES location.

An algorithm for the reconstruction of high-energy neutrino-induced particle showers and its application to the ANTARES neutrino telescope.

A novel algorithm to reconstruct neutrino-induced particle showers within the ANTARES neutrino telescope is presented. The method achieves a median angular resolution of [Formula: see text] for shower energies below 100 TeV. Applying this algorithm to 6 years of data taken with the ANTARES detector, 8 events with reconstructed shower energies above 10 TeV are observed. This is consistent with the expectation of about 5 events from atmospheric backgrounds, but also compatible with diffuse astrophysical flux measurements by the IceCube collaboration, from which 2-4 additional events are expected. A [Formula: see text] C.L. upper limit on the diffuse astrophysical neutrino flux with a value per neutrino flavour of [Formula: see text] is set, applicable to the energy range from 23 TeV to 7.8 PeV, assuming an unbroken [Formula: see text] spectrum and neutrino flavour equipartition at Earth.

Sperm whale long-range echolocation sounds revealed by ANTARES, a deep-sea neutrino telescope.

Despite dedicated research has been carried out to adequately map the distribution of the sperm whale in the Mediterranean Sea, unlike other regions of the world, the species population status is still presently uncertain. The analysis of two years of continuous acoustic data provided by the ANTARES neutrino telescope revealed the year-round presence of sperm whales in the Ligurian Sea, probably associated with the availability of cephalopods in the region. The presence of the Ligurian Sea sperm whales was demonstrated through the real-time analysis of audio data streamed from a cabled-to-shore deep-sea observatory that allowed the hourly tracking of their long-range echolocation behaviour on the Internet. Interestingly, the same acoustic analysis indicated that the occurrence of surface shipping noise would apparently not condition the foraging behaviour of the sperm whale in the area, since shipping noise was almost always present when sperm whales were acoustically detected. The continuous presence of the sperm whale in the region confirms the ecological value of the Ligurian sea and the importance of ANTARES to help monitoring its ecosystems.

Health Data Entanglement and artificial intelligence-based analysis: a brand new methodology to improve the effectiveness of healthcare services.

Healthcare expenses will be the most relevant policy issue for most governments in the EU and in the USA. This expenditure can be associated with two major key categories: demographic and economic drivers. Factors driving healthcare expenditure were rarely recognised, measured and comprehended. An improvement of health data generation and analysis is mandatory, and in order to tackle healthcare spending growth, it may be useful to design and implement an effective, advanced system to generate and analyse these data. A methodological approach relied upon the Health Data Entanglement (HDE) can be a suitable option. By definition, in the HDE a large amount of data sets having several sources are functionally interconnected and computed through learning machines that generate patterns of highly probable future health conditions of a population. Entanglement concept is borrowed from quantum physics and means that multiple particles (information) are linked together in a way such that the measurement of one particle's quantum state (individual health conditions and related economic requirements) determines the possible quantum states of other particles (population health forecasts to predict their impact). The value created by the HDE is based on the combined evaluation of clinical, economic and social effects generated by health interventions. To predict the future health conditions of a population, analyses of data are performed using self-learning AI, in which sequential decisions are based on Bayesian algorithmic probabilities. HDE and AI-based analysis can be adopted to improve the effectiveness of the health governance system in ways that also lead to better quality of care.

Spread of Enterobacter cloacae carrying blaNDM-1, blaCTX-M-15, blaSHV-12 and plasmid-mediated quinolone resistance genes in a surgical intensive care unit in Croatia.

The objective of this study was to describe a hospital cluster of NDM-1-producing Enterobacter cloacae infections observed in the surgical intensive care unit (ICU) of a tertiary-care hospital at Pula, Croatia. NDM-1-producing E. cloacae strains isolated from clinical samples were screened by PCR for the presence of carbapenemases. Genetic relatedness of NDM-1-producing E. cloacae strains was determined by multilocus sequence typing (MLST). During the period October 2013 to April 2014, four patients, with overlapping hospital stay in the surgical ICU, developed severe infections caused by E. cloacae demonstrated to produce carbapenemases. According to MLST, all strains belonged to ST133 and were positive by PCR for the blaNDM-1 carbapenemase gene, for blaCTX-M-15 and blaSHV-12 extended-spectrum ß-lactamase (ESBL) genes, and for blaTEM-1 and blaOXA-1 narrow-spectrum ß-lactamase genes. They were negative for other carbapenemases genes including blaOXA-48, blaVIM and blaKPC as well as for AmpC and the armA and rmtB aminoglycoside resistance genes. All strains were positive for the HI2 replicon, suggesting that an IncHI2 plasmid is likely the plasmid carrying the blaNDM-1 gene. Infection control measures were implemented after the first case although they were not effective in avoiding spread of this organism to other patients in the surgical ICU. In conclusion, the evolving epidemiology of NDM-producing micro-organisms and the interspecies diffusion of this resistance mechanism to emerging pathogens such as E. cloacae necessitate the setting up of strong and urgent joint measures to control the spread of NDM carbapenemase especially in the ICU setting.

Sperm-egg interaction at fertilization: glycans as recognition signals.

This article first examines the events occurring in male and female genital tracts, which prepare human sperm to encounter the egg. Central is a glycoprotein, gp20, homologous to the leukocyte antigen CD52. This protein is secreted in the epididymal cells, inserted in the sperm plasma membrane and exposed in the equatorial region of the head at the end of the capacitation process. The mechanisms and molecules of the first interaction event between gametes in the mollusk bivalve Unio elongatulus and the current state of our knowledge of the same interaction in other species is then considered. The egg of Unio is very peculiar because it is highly polarized. Similar to other well-known egg models, the ligand for recognition is located on the egg coat which is a sort of fibrous network made up of very few glycoproteins, while the receptor is on the sperm surface. The difference is that in this egg, the ligand molecules are not uniformly distributed but are restricted to an area of the egg coat at the vegetal pole, the crater area. The role of carbohydrates in ligand function and of a specific type of oligosaccharide chain in particular, is discussed in the wider context of glycans acting as recognition signals.

The economic burden of HCV-induced diseases in Italy. A probabilistic cost of illness model.

OBJECTIVE: The hepatitis C virus (HCV) induces several pathological conditions worldwide, with a substantial medical and economic burden. The objective of this study was to estimate the average annual cost incurred by the National Health Service (NHS), as well as society, due to HCV in Italy. METHODS: A probabilistic incidence-based cost of illness model was developed to estimate an aggregate measure of the economic burden associated with HCV-induced diseases either in terms of direct or indirect costs. Indirect costs were calculated on the basis of lost productivity according to the human capital approach. A systematic literature review was carried out to identify epidemiological and economic data which were used to inform the model. Furthermore, a one-way probabilistic sensitivity analysis with 5,000 Monte Carlo simulations was performed, in order to test the robustness of the results and define the proper 95% Confidence Interval (CE). RESULTS: Overall, the total economic burden associated with HCV-induced diseases was estimated in €1.06 billion (95%CI: €0.61-€1.63). A percentage of 60.6%  was associated with indirect costs (95% CI: €0.37-€0.99 billion) and 39.4% with direct costs (95% CI: €0.23-€0.65 billion). In chronic hepatitis C, cirrhosis, hepatocellular carcinoma (HCC), liver transplantation and HCV-induced deaths, an average annual economic burden amounting to €0.26 (95%CI: €0.14-€0.41), €0.56 (95%CI: €0.30-€0.89), €0.051 (95%CI: €0.0007-€0.25), €0.05 (95%CI: €0.03-€0.08) and €0.15 (95%CI: €0.07-€0.27) billion respectively, was estimated. CONCLUSIONS: Italy is one of the European countries with the highest number of people affected by chronic HCV infection, the leading cause of cirrhosis, HCC and liver-related death. HCV-induced diseases generate high costs to Italian NHS. These highly debilitating and life-threatening complications generate a rather large amount of indirect costs for the Italian society as well.

A case of Alkhumra virus infection.

Alkhumra virus (ALKV) is an emerging tick-borne flavivirus known to cause a neglected tropical disease in the Middle East. The magnitude of the disease among European returning travelers is still unknown probably because the inadequate knowledge about the real geographic distribution of ALKV infection have limited its diagnosis. Up to now in Italy were reported only three cases; here we report the fourth case of ALKV in a returning traveler from south Egypt.