Daptomycin for the treatment of osteomyelitis and orthopaedic device infections: real-world clinical experience from a European registry.

Osteomyelitis is a serious infection predominantly caused by Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Orthopaedic device-related infections are complex and require a careful combination of surgical intervention and antimicrobial therapy. Daptomycin, a cyclic lipopeptide, effectively penetrates soft tissue and bone and demonstrates rapid concentration-dependent bactericidal activity against Gram-positive pathogens. This retrospective, non-interventional study evaluated clinical outcomes in patients with osteomyelitis or orthopaedic device infections treated with daptomycin from the European Cubicin® Outcomes Registry and Experience (EU-CORE(SM)) study. Patients were treated between January 2006 and April 2012, with follow-up to 2014. Clinical outcomes were assessed as success (cured or improved), failure or non-evaluable. Of 6,075 patients enrolled, 638 (median age, 63.5 years) had primary infections of osteomyelitis or orthopaedic device infections, 224 had non-prosthetic osteomyelitis, 208 had osteomyelitis related to a permanent or temporary prosthetic device, and 206 had orthopaedic device infections. The most commonly isolated pathogen was S. aureus (214 [49.1 %]; 24.8 % were MRSA). Overall, 455 (71.3 %) patients had received previous antibiotic therapy. Patients underwent surgical interventions, including tissue (225 [35.3 %]) and bone (196 [30.7 %]) debridement, as part of their treatment. Clinical success rates were 82.7 % and 81.7 % in S. aureus and coagulase-negative staphylococcal infections. Adverse events (AEs) and serious AEs assessed as possibly related to daptomycin were observed in 6.7 % and 1.9 % of patients, respectively. Daptomycin was discontinued by 5.5 % of patients due to AEs and 10 (1.6 %) deaths were reported. In conclusion, daptomycin was effective and safe in patients with osteomyelitis or orthopaedic device infections.

TD-UAPO diffracted field evaluation for penetrable wedges with acute apex angle.

This study deals with the time domain (TD) diffraction phenomenon related to a penetrable acute-angled dielectric wedge. The transient diffracted field originated by an arbitrary function plane wave is evaluated via a convolution integral involving the TD diffraction coefficients, which are determined here in closed form, starting from the knowledge of the frequency domain counterparts. In particular, the inverse Laplace transform is applied to the uniform Asymptotic physical optics diffraction coefficients valid for the internal region of the wedge and the surrounding space. Diffraction by penetrable wedges in the TD framework is a challenging problem from the analytical point of view, and no other expressions are available in closed form for the diffraction coefficients associated with the considered problem.

Diffraction by 90° penetrable wedges with finite conductivity.

This study concerns the diffraction problem relevant to a plane wave normally incident with respect to a 90° wedge. A penetrable material with finite conductivity forms the structure. A high-frequency solution is here obtained by adopting a physical optics approximation for the equivalent electric and magnetic surface currents involved in the radiation integrals used to represent the fields scattered in the inner region of the wedge and the surrounding space. Uniform asymptotic evaluations of such integrals lead to closed form expressions for the diffraction coefficient in terms of the transition function of the uniform theory of diffraction and the Fresnel coefficients for the reflection and transmission mechanisms. No limitation exists on the loss tangent of the medium. Comparisons with numerical tools assess the effectiveness of the proposed solutions for the field diffracted in the inner and outer regions.

Assessment of SARS-CoV-2 airborne infection transmission risk in public buses.

Public transport environments are thought to play a key role in the spread of SARS-CoV-2 worldwide. Indeed, high crowding indexes (i.e. high numbers of people relative to the vehicle size), inadequate clean air supply, and frequent extended exposure durations make transport environments potential hotspots for transmission of respiratory infections. During the COVID-19 pandemic, generic mitigation measures (e.g. physical distancing) have been applied without also considering the airborne transmission route. This is due to the lack of quantified data about airborne contagion risk in transport environments. In this study, we apply a novel combination of close proximity and room-scale risk assessment approaches for people sharing public transport environments to predict their contagion risk due to SARS-CoV-2 respiratory infection. In particular, the individual infection risk of susceptible subjects and the transmissibility of SARS-CoV-2 (expressed through the reproduction number) are evaluated for two types of buses, differing in terms of exposure time and crowding index: urban and long-distance buses. Infection risk and reproduction number are calculated for different scenarios as a function of the ventilation rates (both measured and estimated according to standards), crowding indexes, and travel times. The results show that for urban buses, the close proximity contribution significantly affects the maximum occupancy to maintain a reproductive number of <1. In particular, full occupancy of the bus would be permitted only for an infected subject breathing, whereas for an infected subject speaking, masking would be required. For long-distance buses, full occupancy of the bus can be maintained only if specific mitigation solutions are simultaneously applied. For example, for an infected person speaking for 1 h, appropriate filtration of the recirculated air and simultaneous use of FFP2 masks would permit full occupancy of the bus for a period of almost 8 h. Otherwise, a high percentage of immunized persons (>80%) would be needed.

Plane-wave diffraction by an obtuse-angled dielectric wedge.

Uniform high-frequency solutions in closed form are derived for the diffraction of a plane wave normally impacting on a penetrable wedge having an obtuse apex angle and arbitrary dielectric permittivity. The approach used here takes advantage of a physical optics approximation for the electric and magnetic equivalent surface currents in the scattering integrals related to the inner region of the wedge and the surrounding space. Numerical tests and comparisons with finite-difference time-domain results demonstrate the accuracy and effectiveness of the proposed solutions.

Epidemiological and clinical features of prosthetic joint infections caused by gram-negative bacteria.

OBJECTIVE: To review the clinical literature focusing on epidemiology, clinical presentation and outcomes of prosthetic joint infections (PJIs) due to gram-negative bacteria (GNB) and to report the experience of a multicentric cohort. PATIENTS AND METHODS: A retrospective, observational, cohort study was performed in three Italian hospitals. All consecutive PJIs caused by GNB over a 12-year period (from May 2007 to March 2018) were enrolled. Epidemiological, clinical, microbiological and therapeutic features were described. Factors related to treatment failure (defined as the occurrence of death, amputation or starting long-term antimicrobial suppression therapy) were analysed with a Cox regression model. RESULTS: A total of 82 PJIs due to GNB (42.7% men; median age 73 years) were studied. The implants included 65 (79.3%) hip, 16 (19.5%) knee and one (1.2%) shoulder. An early PJI was diagnosed in 16.2% of patients, a delayed PJI in 29.4% and a late PJI in 54.4%. The most common isolated organisms were Escherichia coli (21.7%) and Pseudomonas spp. (20.9%). 13.4% of the isolates were carbapenem-resistant bacteria (CRB). In 53.8% of cases a two-stage exchange arthroplasty was performed and in 32.5% a Girdlestone excision arthroplasty. The average therapeutic failure occurred in 17.7% of cases. The therapeutic failure rate of the two-stage was 10%. PJI due to CRB was identified as a potential risk factor for failure (aHR 4.90; IC 95%, 0.96-25.08; p=0.05). The therapeutic failure rate in the CRB group was 50%. CONCLUSIONS: The treatment with the two-stage procedure for PJIs caused by GNB seems to be associated with a low rate of failure, while PJI due to CRB seems to be related to the worst outcome.

Etiology of prosthetic joint infections in a tertiary care centre in Italy.

Prosthetic joint infections (PJIs) represent a severe complication in orthopaedics. Coagulase-negative staphylococci (CoNS) and Staphylococcus aureus represent the most frequent cause, but Gram-negatives have also been reported. With a view to describing the aetiology of PJIs diagnosed from January 2005 to September 2007 at S. Corona Hospital in Pietra Ligure, Italy, we conducted retrospective analysis of pathogens isolated from PJIs by means of surgical specimens, needle aspirates or swabs of fistula (3 samples). During the study period 228 PJIs were described and 141 (62%) were microbiologically documented and evaluated. Early and delayed infections represented 45% of episodes, while late infections were observed in 55%. The aetiology was mono-microbial in 84% of cases, and polymicrobial in 16%. CoNS and S. aureus were the most frequently isolated pathogens. In early and delayed infections methicillin resistant CoNS were 30% and 24%, respectively, while in late infections they were 17%. Methicillin-resistant S. aureus was isolated in 13% of early, 22% of delayed and 15% of late infections. Gram-negatives were described in 16% of episodes without differences being found in the three groups. In our report staphylococci represented the most frequent cause of PJIs. Methicillin-resistant strains were more frequently isolated in early and delayed infections, but their frequency in late episodes was not negligible. Polymicrobial infections and Gram-negative infections were also frequent.

Dysregulation of peripheral and central chemoreflex responses in Chagas' heart disease patients without heart failure.

BACKGROUND: The peripheral and central chemoreflexes are important autonomic mechanisms for regulating breathing and cardiovascular function. Although pathological inflammatory infiltration of the peripheral chemoreceptors and central nervous system has been reported in Chagas' disease, functional evaluation of chemoreflexes has not yet been performed. METHODS AND RESULTS: The hypothesis that chemoreflex function is altered in patients with Chagas' heart disease (CH) but normal left ventricle function was tested in 12 CH patients and 13 matched control subjects. The ventilatory rate, minute ventilation, heart rate, mean arterial pressure, forearm blood flow, forearm vascular resistance, and venous norepi-nephrine responses to hypoxia and hypercapnia were determined. During hypoxia, the decrease in oxygen saturation was smaller in CH patients, despite a similar ventilatory response between groups. Both groups showed an increase in heart rate during hypoxia, but this response was blunted in CH patients. Although the mean arterial pressure response to hypoxia was similar in both groups, forearm vascular resistance significantly decreased in control subjects while remaining unchanged in CH patients. Moreover, a significant increase in plasma norepinephrine levels elicited by stimulation of peripheral chemoreceptors was observed only in the CH group. During hypercapnia, the increase in minute ventilation was smaller in CH patients, who did not exhibit the increase in norepinephrine observed in control subjects. CONCLUSIONS: These data suggest that CH potentiates respiratory, cardiovascular, and autonomic responses to peripheral chemoreceptor activation by hypoxia in patients with normal left ventricular function. The ventilatory and sympathetic responses to central chemoreceptor activation by hypercapnia, however, are significantly blunted.

Cardiovascular effects of short-term growth hormone hypersecretion.

Many studies have shown that acromegaly has relevant effects on cardiovascular system, but few data are available regarding the effects of short-term acromegaly on heart morphology and function. These data would help to clarify the natural history of acromegalic disease and could provide new insight into the mechanisms of GH action on the human heart. Therefore, we studied by Doppler echocardiography a group of 10 young subjects strictly selected as having short-term (<5 yr) uncomplicated acromegaly. The results of this study have shown that shortterm acromegaly is characterized by significantly increased left ventricular mass (P<0.005), with normal relative wall thickness, associated with Doppler indices of diastolic function in the normal range. Furthermore, stroke index and cardiac index were significantly enhanced in the patient group (P<0.01 and P<0.001, respectively), whereas systemic vascular resistance was significantly reduced (P<0.001). In conclusion, our study shows that short-term acromegaly significantly affects the heart, but, at variance with long-term disease, it is characterized by increased left ventricular mass, with eccentric remodeling and normal diastolic function. Moreover, short-term acromegaly induces a high cardiac output state with reduction of systemic vascular resistance.

Gravitoinertial force versus the direction of balance in the perception and control of orientation.

Curthoys and Wade (1990) appeal to land-based data in defending the traditional view that stimulation of the otolith organs leads to perception of the direction of gravitoinertial force. However, such data do not permit rejection of the hypothesis that the perception of orientation is based on the dynamically defined direction of balance, which is qualitatively different from the kinetically defined direction of gravitoinertial force. Furthermore, the approach of Curthoys and Wade is compromised by their failure to consider relations between the perception and control of orientation. Such relations must be considered in developing a general theory of orientation.

Lack of effect of a single oral dose of cyclosporine on systemic blood pressure and on forearm blood flow and vascular resistance in humans.

The acute hemodynamic effect of cyclosporine in man is controversial. A randomized, double blind, placebo-controlled, cross-over study was undertaken to evaluate the effect of a single oral dose of cyclosporine (20 mg/kg body weight) on mean blood pressure (MBP), heart rate (HR), forearm blood flow (FBF), and vascular resistance (FVR) in 16 healthy adult subjects. Subjects were studied twice, with an intervening period of 2 weeks, before and after the administration of either cyclosporine or the vehicle olive oil. Blood pressure was measured on brachial and digital arteries. After 30 min of rest, basal measurements were obtained and individuals were randomly assigned to receive either cyclosporine or the vehicle, and the same measurements were repeated 2 h later. Mean whole blood levels of cyclosporine were 1542+/-387 ng/mL (range 1000 to 2550) 2 h after the administration of a single oral dose of cyclosporine. Cyclosporine did not cause any significant change in the hemodynamic parameters when compared with vehicle. Pre- and post-cyclosporine data were as follows (means +/-/SD): MBP (determined by Finapres on the digital artery), 92+/-10 v 95+/-11 mm Hg; HR, 66+/-10 v 68+/-11 beats/min; FBF, 3.90+/-1.3 v 3.8+/-1.8 mL/ 100 mL/min; and FVR, 28+/-9 v 33 +/-18 units, respectively. For the vehicle the results were: MBP, 94+/-9 v 94+/-9; HR, 67+/-9v 67 /-11; FBF, 3.3+/-1.6 v 3.2+/-2.0; FVR, 35+/-14 v 37+/-15, respectively. These figures did not differ from those obtained with the auscultatory method applied to the brachial artery among 10 selected subjects studied with Finapres. In conclusion, we found no evidence that at supratherapeutic doses cyclosporine causes acute increase in blood pressure or peripheral vasoconstriction in humans.

The role of balance dynamics in the active perception of orientation.

The Stoffregen and Riccio (1988) hypothesis that perceived orientation is determined primarily by balance dynamics was tested. Perception of orientation was evaluated in the context of a task that required Ss to control the roll orientation of a device in which they were seated. The device's direction of balance was manipulated across trials and thus was independent of gravity. Eighteen Ss participated in the investigation. After each trial, Ss estimated their mean tilt with respect to upright. Correlations of perceived tilt with tilt from balance were consistently higher than the correlations with gravity tilt. The dominance of balance over gravity depended on the magnitude of tilt from balance.

Detection of the traversability of surfaces by crawling and walking infants.

In four studies we investigated the perception of the affordance for traversal of a supporting surface. The surface presented was either rigid or deformable, and this property was specified either optically, haptically, or both. In Experiment 1A, crawling and walking infants were presented with two surfaces in succession: a standard surface that both looked and felt rigid and a deforming surface that both looked and felt nonrigid. Latency to initiate locomotion, duration of visual and haptic exploration, and displacement activity were coded from videotapes. Compared with the standard, the deforming surface elicited longer latency, more exploratory behavior, and more displacement in walkers, but not in crawlers, suggesting that typical mode of locomotion influences perceived traversability. These findings were replicated in Experiment 1B, in which the infant was presented with a dual walkway, forcing a choice between the two surfaces. Experiments 2, 3A and B, and 4A and B investigated the use of optical and haptic information in detecting traversability of rigid and nonrigid surfaces. Patterns of exploration varied with the information presented and differed for crawlers and walkers in the case of a deformable surface, as an affordance theory would predict.

Phaeomelanin versus eumelanin as a chemical indicator of ultraviolet sensitivity in fair-skinned subjects at high risk for melanoma: a pilot study.

It is now generally agreed that solar exposure is a major external factor in the causation of cutaneous melanoma in light skinned populations with red hair and a marked susceptibility to the acute effects of ultraviolet (UV) radiation. In the present study, we investigated the existence of a possible relationship between hair melanin composition and minimal erythema dose (MED), as an indicator of UV sensitivity, in a group of 15 healthy red-haired subjects aged 20-46 years. In spite of comparable skin and hair colour, marked variations were observed in the MED values as well as in the hair melanin composition. Phaeomelanin levels varied in the range 0.026-0.53% w/w and were generally comparable to or higher than eumelanin levels (0.042-0.17% w/w). No significant relationship was found between MED values and phaeomelanin, eumelanin or total melanin (eumelanin plus phaeomelanin) content. Notably, however, a gross positive correlation was found between the eumelanin/phaeomelanin ratio and the MED values. These results would suggest that a high UV sensitivity is associated with high phaeomelanin and low eumelanin levels, and point to the eumelanin/phaeomelanin ratio as a novel chemical parameter that could be used for predicting individuals at high risk for skin cancer and melanoma.

Spinal cord involvement and systemic lupus erythematosus: clinical and magnetic resonance findings in 5 patients.

We report the clinical, magnetic resonance imaging (MRI) and laboratory findings in 5 patients with clinical spinal cord involvement with an acute or subacute course; in two of the patients the myelitic episode preceded, in one it was concomitant to, and in two it followed the diagnosis of systemic lupus erythematosus (SLE). The marked clinical and MRI heterogeneity detected in our patients suggests that various factors may be implied in the pathogenesis of spinal cord involvement in SLE. The possibility of a future evolution to SLE should be kept in mind in women presenting spinal cord involvement with no other explanation, and should be assessed by means of extensive and repeated clinical and laboratory evaluations.

Postural orientation: age-related changes in variability and time-to-boundary.

The relation between age-specific postural instability and the detection of stability boundaries was examined. Balance control was investigated under different visual conditions (eyes open/closed) and postural orientations (forward/backward lean) while standing on a force platform. Dependent variables included center of pressure variability and the time-to-contact of the center of pressure with the stability boundaries around the feet (i.e., time-to-boundary). While leaning maximally, older individuals (ages 55-69) showed increased center of pressure variability compared to no lean, while younger subjects (ages 24-38) showed a decrease. These significant differences were found only in anterior-posterior direction. No significant age-specific differences were found between eyes open and eyes closed conditions. Time-to-boundary analysis revealed reduced spatio-temporal stability margins in older individuals in both anterior-posterior and medio-lateral directions. Time-to-boundary variability, however, was not significantly different between the groups in both medio-lateral and anterior-posterior direction. These results show the importance of boundary relevant center of pressure measures in the study of postural control, especially concerning the lateral instability often observed in older adults.

Autonomic abnormalities demonstrable in young normotensive subjects who are children of hypertensive parents.

Although a slightly elevated office blood pressure (BP) has been reported in several studies, little is known about the prolonged resting blood pressure, heart rate (HR) and baroreflex sensitivity (BRS) of prehypertensive subjects with a family history of hypertension. Office blood pressure, prolonged resting (1 h) BP and HR were measured in 25 young normotensives with a positive family history of hypertension (FH+) and 25 young normotensives with a negative family history of hypertension (FH-), matched for age, sex, and body mass index. After BP and HR measurements, blood samples were collected for the determination of norepinephrine, plasma renin activity and aldosterone levels, and baroreflex sensitivity was then tested. Casual BP, prolonged resting BP and heart rate were significantly higher in the FH+ group (119.9 +/- 11.7/78.5 +/- 8.6 mmHg, 137.3 +/- 12.3/74.4 +/- 7.9 mmHg, 68.5 +/- 8.4 bpm) compared to the FH- group (112.9 +/- 11.4/71.2 +/- 8.3 mmHg, 128.0 +/- 11. 8/66.5 +/- 7.4 mmHg, 62.1 +/- 6.0 bpm). Plasma norepinephrine level was significantly higher in the FH+ group (220.1 +/- 104.5 pg/ml) than in the FH- group (169.1 +/- 63.3 pg/ml). Baroreflex sensitivity to tachycardia (0.7 +/- 0.3 vs 1.0 +/- 0.5 bpm/mmHg) was depressed in the FH+ group (P<0.05). The FH+ group exhibited higher casual blood pressure, prolonged resting blood pressure, heart rate and plasma norepinephrine levels than the FH- group (P<0.05), suggesting an increased sympathetic tone in these subjects. The reflex tachycardia was depressed in the FH+ group.

[Churg-Strauss syndrome: is it a rare disease?]. / Sindrome di Churg-Strauss: è una malattia rara?

We describe four patients with Churg-Strauss syndrome admitted to the hospital in 1988. Some clinical and histological features of particular relief are present in these cases. All patients had been treated with corticosteroids and they are now in remission. Our work suggests that Churg-Strauss syndrome is not a rare disease and that an early diagnosis and appropriate therapy may influence favourably at least long term survival.

[Carotid atherosclerosis and thrombotic stroke. Diagnostic and therapeutic perspectives]. / Aterosclerosi carotidea ed ictus aterotrombotico. Attuali prospettive diagnostiche e terapeutiche.

Carotid atherosclerotic lesions can be studied with color-Doppler ultrasonography vascular systems. Ultrasonography of the carotid plaques at major risk for the development of cerebrovascular ischemic events showed the following characteristics: irregular surface, degree of stenosis > 70%, intimal hemorrhage and ulceration. The plaques with these ultrasonography patterns have to be considered for surgical approach (TEA). The other patients with carotid atherosclerotic lesions will be initially treated with diet and changes of life style to obtain the correction of cardiovascular risk factors (i.e. hypertension, hypercholesterolemia, diabetes). Furthermore, medical therapy with antithrombotic agents will be instituted which, used with good results also in acute cerebral stroke, proved to be effective in the reduction of vascular events in patients with extracranial atherosclerotic plaques. However, it has not been clarified if the positive effect of antiaggregation therapy in carotid atherosclerosis is due to the inhibition of the progression and plaque growth or if other hemorheological factors are involved.

[Gigantic fibroadenoma of the breast in an adolescent. Description of a clinical case]. / Fibroadenoma gigante della mammella in adolescente. Descrizione di un caso clinico.

A case of giant fibroadenoma in a girl of 14 is reported. This case emerged from an examination of about 380 patients observed at the Senology Clinic of the S. Maria di Loreto Hospital (USL 44) in the last 3 years. A statistical contribution is made to the study of breast pathologies in pubertal age and stress is laid on the importance of mass screening among adolescents.