Mortality and prognostic factors in patients with bullous pemphigoid: a retrospective multicenter Italian study.

INTRODUCTION: Bullous pemphigoid is the most common autoimmune bullous dermatosis. In recent years several studies have tried to identify the main factors of the disease related with an increased risk of death. The aim of this multicenter Italian study was to assess the risk score of death considering epidemiologic, clinical, immunological, and therapeutic factors in a cohort of patients affected by bullous pemphigoid and try to identify the cumulative survival up to 120 months. METHODS: We retrospectively reviewed the medical records of patients with bullous pemphigoid who were diagnosed between 2005 and 2020 in the 12 Italian centers. Data collected included sex, age at the time of diagnosis, laboratory findings, severity of disease, time at death/censoring, treatment, and multimorbidity. RESULTS: A total of 572 patients were included in the study. The crude mortality rate was 20.6%, with an incidence mortality rate of 5.9 × 100 person/year. The mortality rate at 1, 3, 5, and 10 years was 3.2%, 18.2%, 27.4% and 51.9%, respectively. Multivariate model results showed that the risk of death was significantly higher in patients older than 78 years, in presence of multimorbidity, anti-BP180 autoantibodies >72 U/mL, or anti-BP230 > 3 U/mL at diagnosis. The variables jointly included provided an accuracy (Harrel's Index) of 77% for predicting mortality. CONCLUSION: This study represents the first nationwide Italian study to have retrospectively investigated the mortality rates and prognostic factors in patients with bullous pemphigoid. A novel finding emerged in our study is that a risk prediction rule based on simple risk factors (age, multimorbidity, steroid-sparing drugs, prednisone use, and disease severity) jointly considered with two biomarkers routinely measured in clinical practice (anti-BP230 and anti-BP180 autoantibodies) provided about 80% accuracy for predicting mortality in large series of patients with this disease.

Real-world effectiveness and safety of Guselkumab for the treatment of psoriasis: a 6-month prospective study in a series of psoriatic patients.

OBJECTIVE: Guselkumab is a fully human monoclonal IgG1 antibody which, by selectively binding to the p19 subunit of IL-23, prevents it from binding to the IL-23 receptor on the cell surfaces. To date, no prospective data are available on the efficacy and safety of this drug in everyday clinical practice in patients with psoriasis (PSO). MATERIALS AND METHODS: This is a longitudinal, single arm, real-world, prospective study to investigate the effect of Guselkumab on PSO and quality of life (DLQI) in 44 PSO patients. Outcomes were PASI, BSA, DLQI at 3 and 6 months. RESULTS: The longitudinal analysis showed that PASI improved from a median value of 24.1 at baseline to 2.0 at 6-months and this was also true for BSA (from 23.0 to 2.0) and DLQI (from 24.0 to 2.5) (all p<0.001). At 6-months, PASI75, PASI90 and PASI100 were 95.5%, 59.1% and 16%, respectively. The PSO improvement related with the increase of DLQI (∆PASI vs. ∆DLQI, r=0.77, p<0.001). No clinically relevant adverse events were observed. CONCLUSIONS: This study demonstrates the effectiveness and safety of Guselkumab on PSO in real world and shows that the reduction of PSO severity due to the drug is directly related with the improvement of quality of life in this patient population.

Value of clinical features to differentiate refractory epilepsy from mimics: a prospective longitudinal cohort study.

BACKGROUND AND PURPOSE: Misdiagnosis of refractory epilepsy (rE) is common and such patients experience a long diagnostic delay. Our aim was to identify key clinical/laboratory factors in order to obtain an alternative diagnosis in patients referred for rE. METHODS: Between January 2010 and December 2015, 125 consecutive patients with a diagnosis of rE were prospectively enrolled. All patients underwent a comprehensive neurological, neuropsychiatric and cardiological evaluation, and had an observation time of at least 1 year after the study entry. RESULTS: Diagnosis of rE was confirmed in 104/125 (83.2%) patients (55 women, mean age 38.8 ± 14.3 years). Thirteen/125 patients (10.4%, seven women, mean age 50.8 ± 20.9) were diagnosed with syncope, which was cardiac/cardio inhibitory in 9/13 (69%). The remaining 8/125 patients (6.4%, six women, mean age 41.2 ± 14.6 years) were diagnosed with psychogenic non-epileptic seizures. Age at onset had a high accuracy in differentiating patients with syncope from others, with the best cut-off age at 35 years and above. Abnormal brain magnetic resonance imaging (MRI) had a significant yield of about 70% in rE. A diagnostic model including age at onset and brain MRI was highly accurate in differentiating patients with syncope from others. In patients with cardiac/cardio inhibitory syncope, the point score of historical features was ≥1 and falsely favoured the diagnosis of epileptic seizures. CONCLUSIONS: This prospective cohort study identifies rE mimics who are at high risk of morbidity and mortality. rE starting in adulthood should raise a high suspicion of cardiac syncope. Brain MRI is accurate in differentiating rE from other conditions.

Transition from Coherent to Stochastic electron heating in ultrashort relativistic laser interaction with structured targets.

Relativistic laser interaction with micro- and nano-scale surface structures enhances energy transfer to solid targets and yields matter in extreme conditions. We report on the comparative study of laser-target interaction mechanisms with wire-structures of different size, revealing a transition from a coherent particle heating to a stochastic plasma heating regime which occurs when migrating from micro-scale to nano-scale wires. Experiments and kinetic simulations show that large gaps between the wires favour the generation of high-energy electrons via laser acceleration into the channels while gaps smaller than the amplitude of electron quivering in the laser field lead to less energetic electrons and multi-keV plasma generation, in agreement with previously published experiments. Plasma filling of nano-sized gaps due to picosecond pedestal typical of ultrashort pulses strongly affects the interaction with this class of targets reducing the laser penetration depth to approximately one hundred nanometers. The two heating regimes appear potentially suitable for laser-driven ion/electron acceleration schemes and warm dense matter investigation respectively.

Migraine with aura white matter lesions: preliminary data on clinical aspects.

A few clinic-based magnetic resonance imaging studies report an increased risk of signal abnormalities in migraineurs brain's white matter, especially in migraine with aura subjects. A vascular genesis has been hypnotized and migraine with aura was considered an independent risk factor for stroke. Available data of magnetic resonance imaging alterations are often nonspecific and sometimes controversial. The aim of our study is to investigate migraine with aura patients with standardized brain magnetic resonance imaging to detect and to quantify the presence of white matter lesions and to analyze their relation with clinical data. We report preliminary data about first 90 subjects. We did not recognize any clinical aspect in close relationship with these alterations. The only clinical feature that seems to play a role in the presence of alterations is the age, and only in migraineurs women.

Coalescence of silver clusters by immersion in diluted HF solution.

The galvanic displacement deposition of silver on H-terminated Si (100) in the time scale of seconds is instantaneous and characterized by a cluster density of 10(11)-10(12) cm(-2). The amount of deposited Ag follows a t(1/2) dependence in agreement with a Cottrell diffusion limited mechanism. At the same time, during the deposition, the cluster density reduces by a factor 5. This behavior is in contrast with the assumption of immobile clusters. We show in the present work that coalescence and aggregation occur also in the samples immersed in the diluted hydrofluoric acid (HF) solution without the presence of Ag(+). Clusters agglomerate according to a process of dynamic coalescence, typical of colloids, followed by atomic redistribution at the contact regions with the generation of multiple internal twins and stacking-faults. The normalized size distributions in terms of r/rmean follow also the prediction of the Smoluchowski ripening mechanism. No variation of the cluster density occurs for samples immersed in pure H2O solution. The different behavior might be associated to the strong attraction of clusters to oxide-terminated Si surface in presence of water. The silver clusters are instead weakly bound to hydrophobic H-terminated Si in presence of HF. HF causes then the detachment of clusters and a random movement on the silicon surface with mobility of about 10(-13) cm(2)/s. Attractive interaction (probably van der Waals) among particles promotes coarsening.

Pro- and anti-inflammatory cytokine gene expression in subcutaneous and visceral fat in severe obesity.

BACKGROUND AND AIMS: Pro-inflammatory molecules produced by adipose tissue have been implicated in the risk of cardiovascular (CV) disease in obesity. We investigated the expression profile of 19 pro-inflammatory and seven anti-inflammatory genes in subcutaneous adipose tissue (SAT) and in visceral adipose tissue (VAT) in 44 severely obese individuals who underwent bariatric surgery. METHODS AND RESULTS: SAT and VAT expressed an identical series of pro-inflammatory genes. Among these genes, 12 were significantly more expressed in SAT than in VAT while just one (IL18) was more expressed in VAT. The remaining genes were equally expressed. Among pro-inflammatory cytokines, both IL6 and IL8 were about 20 times more intensively expressed in SAT than in VAT. The expression of nine genes was highly associated in SAT and VAT. Only for three pro-inflammatory cytokines (IL8, IL18, SAA1) in SAT the gene expression in adipose tissue associated with the circulating levels of the corresponding gene products while no such an association was found as for VAT. CONCLUSIONS: The expression of critical pro-inflammatory genes is substantially higher in SAT than in VAT in individuals with morbid obesity. The variability in circulating levels of pro-inflammatory cytokines is, in small part and just for three pro-inflammatory cytokines, explained by underlying gene expression in SAT but not in VAT. These results point to a compartment-specific adipose tissue contribution to inflammation in obesity and indicate that abdominal SAT contributes more than VAT to the pro-inflammatory milieu associated with severe obesity.

Chasing bacteria within the cells using levofloxacin-loaded hyaluronic acid nanohydrogels.

In the present work, an innovative approach based on the delivery of levofloxacin (LVF) from polysaccharide nanohydrogels for the treatment of bacterial intracellular infections is described. The nanohydrogels (NHs) were obtained by self-assembling of the hyaluronic acid-cholesterol amphiphilic chains in aqueous environment. LVF, a fluoroquinolone antibiotic scarcely efficient in intracellular infections, was entrapped within such NHs by nanoprecipitation, thus forming a drug delivery system (LVF-NHs) that was tested for its activity on different bacteria strains. The MIC values of levofloxacin-loaded nanohydrogels were determined for Staphylococcus aureus and Pseudomonas aeruginosa strains and compared to those obtained using free LVF. The intracellular antimicrobial activity of LVF-NHs and free LVF was compared on HeLa epithelial cell line infected by the above mentioned bacteria, and the increase in antibacterial efficacy of LVF-NHs with respect to that of free LVF was evidenced. The obtained results allow to conclude that this new approach can be considered as really promising method for intracellular infection treatments.

Sexual dysfunction after elective endovascular or hand-assisted laparoscopic abdominal aneurysm repair.

OBJECTIVE: To evaluate the incidence of sexual dysfunction and retrograde ejaculation after elective endovascular aneurysm repair (EVAR) and hand-assisted laparoscopic surgery (HALS) for abdominal aortic aneurysm (AAA). METHODS: A total of 100 patients eligible for elective repair of infrarenal AAAs were randomised in two groups: EVAR and HALS. The quality of sexual function was evaluated using the International Index of Erectile Function (IIEF), a 15-item questionnaire. Patients completed the IIEF preoperatively and at 12 months. The incidence of retrograde ejaculation was also evaluated. RESULTS: One- and 12-month mortality rates were zero. Three patients in the EVAR group (6%) and two patients in the HALS group (4%) reported an erectile dysfunction (p = NS). The quality of sexual function at 1 year was similar in both groups: total score of 66 in the EVAR group versus 68 in the HALS group (p = 0.66). Retrograde ejaculation was detected in three cases in the HALS group versus no case in the EVAR group. CONCLUSIONS: The HALS technique could be a minimally invasive alternative for sexually active males unsuitable for EVAR repair.

Temperature and concentration dependence of SANS spectra of aqueous solutions of short-chain amphiphiles.

The small-angle neutron scattering (SANS) of some aqueous solutions of short-chain amphiphiles (glycols, diglycols, diols) has been measured as a function of concentration and temperature. The analysis of the spectra in terms of the Teubner-Strey phenomenological formula indicates that, on increasing the concentration of the amphiphile, the structure of all these systems evolves in a similar way, i.e. a transition from disordered structures toward correlated aggregates (microstructures). The transition is depressed by increasing the temperature.

[Carpal tunnel syndrome among cashiers in commercial businesses]. / La sindrome del tunnel carpale in cassiere di aziende commerciali.

The Check-out assistants represent a working sector at risk of Work Related Musculo Skeletal Disorders (WMSDs). The aim of our study is to evaluate carpal tunnel syndrome's incidence in check out assistants. Our search was carried out on a sample of 695 female check-out assistants,after a specific risk's valutazion witch "chec-list application", during health surveillance. Subjects with an pand's painful symptoms or paraesthesias along territory of median were submitted to tests thath revial compression of median at wrist: Phalen and Tinel tests. Who were positive to painful symptoms or paraesthesias in both tests, were subjected to electromyographia (E.M.G.), gold standard for carpal tunnel Syndrome diagnosis. This sample was compared with a control group no-exposed to specific risk (all teachers) of equal number, age, sex and working age of our sample. Our results point out that: our study sample show more symptoms and carpal tunnel Syndrome than the control group; tere aren't statistically meaningful differences between test's positive subjects amd EMG positive subjects. We demonstrated that a careful anamnesis and objective exam can replace EMG.

Shear and longitudinal viscosity of non-ionic C12E8 aqueous solutions.

We present an extensive set of measurements of steady shear viscosity (eta degrees(s)), longitudinal elastic modulus (M'), and ultrasonic absorption (alpha) in the one-phase isotropic liquid region of the non-ionic surfactant C12E8 aqueous solutions. Within a given temperature interval, this phase extends along the entire surfactant concentration range that could be fully covered in the experiments. In agreement with previous studies, the overall results support the presence of two separated intervals of concentration corresponding to different structural properties. In the surfactant-rich region the temperature dependence of eta degrees(s) follows an equation characteristic of glass-like systems. The ultrasonic absorption spectra show unambiguous evidence of viscoelastic behavior that can be described by a Cole-Cole relaxation formula. In this region, when both the absorption and the frequency are scaled by the static shear viscosity (eta degrees(s)), the scaled attenuation reduces to a single universal curve for all temperatures and concentrations. In the water-rich region the behavior of eta degrees(s), M', and alpha are more complex and reflect the presence of dispersed aggregates whose size increases with temperature and concentration. At these concentrations the ultrasonic spectra are characterized by a multiple decay rate. The high-frequency tail falls in the same frequency range seen at high surfactant content and exhibits similar behaviors. This contribution is ascribed to the mixture of hydrophilic terminations and water present at the micellar interfaces that resembles the condition of a concentrated polymer solution. An additional low-frequency contribution is also observed, which is ascribed to the exchange of water molecules and/or surfactant monomers between the aggregates and the bulk solvent region.

Clinical and muscle magnetic resonance imaging study of an Italian family with autosomal dominant inclusion body myopathy not linked to known genetic loci.

The objective was to report a clinical, pathological and muscle magnetic resonance (MR) study of an Italian family with an autosomal dominant inclusion body myopathy (AD-IBM). Eight subjects (age range 20-56 years; 5 females and 3 males) belonging to four generations were studied. Onset of disturbances (distal weakness at lower limbs) ranged from 20 to 28 years. CK levels were increased to five times. Only in an early stage oedema of involved muscles has been demonstrated by muscle MR. Quadriceps femoris was characteristically spared; in the last phases a mild involvement of the vasti became evident with persistent sparing of the rectus femori. Rimmed vacuoles and hyperphosphorylated tau filaments were evident at muscle biopsy. Linkage analysis excluded the association of the disease to chromosome loci 14q11, 17p13.1, 2p13, 19p13. The study suggests that quadriceps sparing is a characteristic feature also of AD-IBM. This finding could represent a muscle-image hallmark helpful in diagnosis of autosomal dominant muscular disorders.

Spirometric function in non-smoking workers exposed to aluminum.

BACKGROUND: Exposure to aluminum (Al) causes the onset of respiratory disorders. This study is aimed at providing further information on how occupational exposure to Al affects the respiratory apparatus in healthy non-smokers, with particular attention to respiratory function. METHODS: A group of 50 male shipyard workers who were exposed to Al underwent medical examination, standard chest X-rays and spirometry in accordance with the C.E.C.A. protocol. The data were compared with those of a homogeneous group of controls, all with blood aluminum (AlB) levels below 7.5 ng/ml. Statistical analysis was performed on the following spirometric parameters: vital capacity (VC), forced vital capacity (FVC), maximum forced expiratory volume in 1 s (FEV1), and mean forced expiratory flow during mid-half of FVC (FEF(25-75%)). Environmental Al levels were also measured at the various workstations. RESULTS: Fifty male workers with an average age 31.82 +/- 5.05 years, occupational exposure of 11.81 +/- 3.71 years, presented with average AlB levels of 32.64 +/- 8.69 ng/ml. Environmental monitoring displayed Al levels higher than TLV TWA for all the workstations studied. None of the sample displayed significant pathological conditions. Statistical comparison of the spirometric parameters showed a decrease in the examined values in exposed workers. This decrease was found to be directly proportional to the AlB level. CONCLUSION: The authors conclude that Al affects respiratory function and that limit values should be reassessed.

Small-angle neutron scattering studies of aqueous solutions of short-chain amphiphiles.

We present small angle neutron scattering measurements on binary aqueous solutions of some short-chain amphiphiles (diols, triols, glycols and diglycols) at room temperature. The spectra were analysed in terms of the Teubner-Strey phenomenological formula which allows to obtain a measure for the amphiphilicity strength of each system (amphiphilicity factor fa). In some systems, however, other models, valid for micellar solutions, give also a good representation of the spectra. As a result, we find that, independently of the type of hydrophilic group side (oxydrilic or oxirane), these systems cover the entire accessible amphiphilicity scale ( -1 < fa < 1). Some disordered systems (fa > 1) presumably are able to form micelle-like aggregates.

Multiple coronary artery aneurysms in a child with neurofibromatosis type 1.

UNLABELLED: A number of frequently unrecognised vascular manifestations have been described in patients with neurofibromatosis type 1 (NF1), including involvement of the great vessels, cerebral, visceral and renal arteries. Rarely, changes in the coronary arteries have been reported in adults with NF1. We report on a 16-year-old boy affected by NF1 with dysmorphic features and three aneurysms in the mid-portion of the left descending coronary artery disclosed by chance during investigation for a malignant peripheral nerve sheath tumour. Molecular analysis detected a gross de novo deletion in the NF1 gene. The boy had had no previous cardiac symptoms but died suddenly after developing signs and symptoms suggestive of myocardial infarction. CONCLUSION: To the best of our knowledge, this represents the first report of multiple lesions in the coronary arteries in a child affected by neurofibromatosis type 1 with a known deletion of the neurofibromatosis type 1 gene.

High Resolution Measurements of Two-dimensional Dopant Diffusion in Silicon.

We report detailed experimental results on the electrochemical selective etching of doped Si. By using transmission electron microscopy analyses and spreading resistance measurements we investigated the dependence of the etching selectivity on the different parameters of the electrochemical cell, i.e., bias voltage and chemical solution. In B-doped samples immersed in buffered HF, the increase of bias voltage from 0.5 to 1 V produces a slight improvement of the etching selectivity and a B concentration as low as 1 x 10(17) cm(-3) can be successfully delineated at 1 V. A further improvement is achieved by using HF:HNO(3):CH(3)COOH or HF:HCl chemical mixtures for which the delineation sensitivity approaches the value of 1 x 10(16) cm(-3). In buffered HF As-doped regions can be delineated to a concentration of 2 x 10(17) cm(-3), independently of the bias voltage, in the range 2-4 V. These results were used to measure the 2D doping diffusion profiles in silicon wafers patterned with polycrystalline Si strips and implanted with As or B, by using different tilt and twist angles. The high resolution of the electrochemical delineation allowed us to evaluate very accurately the effects of the implant angles on the lateral doping distribution.