[Therapeutic Plasma Exchange in a Patient with Chronic Hemodialysis and a New Diagnosis of Myasthenia Gravis].

Case ReportC.S.T. (♂, 71 years old) is a patient with multiple and severe comorbidities, undergoing thrice-weekly chronic hemodialysis since 2008 due to the progression of post-lithiasic uropathy. Over the past 2 months, the patient had been experiencing progressive ptosis of the eyelids, muscle weakness, and ultimately dysphagia and dysarthria that emerged in the last few days. Urgently admitted to the Neurology department, electromyography (EMG) was performed, leading to a diagnosis of predominant cranial myasthenia gravis (with borderline anti-acetylcholine receptor antibody serology). Prompt treatment with pyridostigmine and steroids was initiated. Considering the high risk of acute myasthenic decompensation, therapeutic plasma exchange (TPE) with centrifugation technique was promptly undertaken after femoral CVC placement. TPE sessions were alternated with hemodialysis. The patient's condition complicated after the third TPE session, with septic shock caused by Methicillin-Sensitive Staphylococcus Aureus (MSSA). The patient was transferred to the Intensive Care Unit (ICU). Due to hemodynamic instability, continuous veno-venous hemodiafiltration (CVVHDF) with citrate anticoagulation was administered for 72 hours. After resolving the septic condition, intermittent treatment with Acetate-Free Biofiltration (AFB) technique was resumed. The patient completed the remaining three TPE sessions and, once the acute condition was resolved, was transferred back to Neurology. Here, the patient continued the treatment and underwent a rehabilitation program, showing significant motor and functional recovery until discharge. Conclusions. The multidisciplinary interaction among Nephrologists, Neurologists, Anesthesiologists, and experts from the Immunohematology and Transfusion Medicine Service enabled the management and treatment of a rare condition (MG) in a high-risk chronic hemodialysis patient.

[New Mutation of CYP24A1 in a Case of Idiopathic Infantile Hypercalcemia Diagnosed in Adulthood].

Mutations in the 24-hydroxylase gene CYP24A1 have been recognized as causes of childhood idiopathic hypercalcemia (IIH), a rare disease (incidence <1:1,000,000 live births) characterized by increased vitamin D sensitivity, with symptomatic severe hypercalcemia. IIH was first described in Great Britain two years after the start of a program of vitamin D supplementation in milk for the prevention of rickets, manifesting in about 200 children with severe hypercalcemia, dehydration, growth failure, weight loss, muscle hypotonia, and nephrocalcinosis. The association between the epidemic occurrence of IIH and vitamin D administration was quickly attributed to intrinsic hypersensitivity to vitamin D, and the pathogenic mechanism was recognized in the inactivation of Cytochrome P450 family 24 subfamily A member 1 (CYP24A1), which was identified as the molecular basis of the pathology. The phenotypic spectrum of CYP24A1 mutation can be variable, manifesting predominantly with childhood onset and severe symptomatology (severe hypercalcemia, growth retardation, lethargy, muscle hypotonia, dehydration), but also with juvenile-adult onset forms with nephrolithiasis, nephrocalcinosis, and alterations in phosphocalcium homeostasis. We describe the case of a patient in whom the diagnosis of IIH was made in adulthood, presenting with finding of nephrocalcinosis in childhood, and with subsequent onset of severe hypercalcemia with hypercalciuria, hypoparathyroidism, hypervitaminosis D, and recurrent renal lithiasis. Genetic investigation revealed the presence in homozygosity of the c_428_430delAAG_p.Glu143del variant in the CYP24A1 gene with autosomal recessive transmission, a mutation not reported in the literature.

High stability microwave discharge ion sources.

A new plasma heating mechanism for Microwave Discharge Ion Sources (MDIS) was discovered. Unprecedented beam stability was observed during the commissioning of the Proton Source for the European Spallation Source (PS-ESS) where several thousand source configurations were tested using a custom software tool. Data analysis and plasma simulation revealed that the new behaviour is generated by a completely new plasma heating schema activated by a precise magnetic configuration peculiarity. The stability showed in this configuration, denominated High Stability Microwave Discharge Ion Source (HSMDIS), is excellent and the emittance of the produced beam is lower than produced by standard MDIS configuration. High linearity between power and beam current was observed making easier the use of the source. This new mode of operation can be easily implemented in all existing sources.

Rituximab in people living with HIV affected by immune-mediated renal diseases: a case-series.

Over the last two decades, rituximab (RTX) has played an important role in the treatment of some lymphoproliferative malignancies and immune-mediated diseases. RTX administration is generally safe and well-tolerated, but side effects including late-onset neutropenia, hypogammaglobulinemia, hepatitis B reactivation and rare cases of progressive multifocal leukoencephalopathy have been observed after its administration. Although there are no absolute contraindications regarding its use in people living with HIV (PLWH), the prescription of this drug has been principally limited in patients with oncohematological diseases. In this report, we described the outcome of four PLWH who underwent RTX therapy after the diagnosis of immune-mediated renal disease. The main RTX-associated adverse effects were leukopenia, late-onset neutropenia and decline of CD4+ and CD8+ T-cell counts. In addition, two of the four patients experienced pneumonia requiring hospitalization within six months from the last RTX infusion. We suggest that RTX should be used with caution in PLWH until further evidence emerges on its safety profile in this vulnerable population.

Role of saccharides on thermal stability of phycocyanin in aqueous solutions.

The effect of heat and equivalent thermal effect ( [Formula: see text] ) on discolouration of Spirulina algae extracts in water, sucrose and trehalose solutions at different concentration was investigated and kinetics of phycocyanin degradation evaluated by spectrophotometric and circular dichroism. At constant temperature, colour loss increased at increasing time and decreased at increasing solute concentration. Circular dichroism confirmed relation between colour loss and protein structure destabilization, and the thermostabilising effect of saccharides with sucrose performing better than trehalose. Apparent constant rate values determined by the Weibullian probabilistic model describe the corresponding phycocyanin degradation kinetics; a linear correlation between the activation energy and aw of the solutions has been found. Origin of phycocyanin and system saccharide concentration resulted significant discriminant factors on the discolouration when [Formula: see text] was taken into account. Results may find application in product formulation and processing optimisation, thereby the use of Spirulina extracts as colouring foodstuff could be enhanced.

Physician-patient communication and patient-reported outcomes in the actinic keratosis treatment adherence initiative (AK-TRAIN): a multicenter, prospective, real-life study of treatment satisfaction, quality of life and adherence to topical field-directed therapy for the treatment of actinic keratosis in Italy.

BACKGROUND: Patients with multiple actinic keratoses (AKs) should be treated with field-directed therapy. Such treatments challenge patients' adherence due to out-of-pocket costs, length of treatment and severity of local skin reactions (LSRs). Effective physician-patient communication (PPC) may buffer therapy-related distress, thus improving quality of life, treatment satisfaction and adherence. OBJECTIVES: We evaluated the interplay between PPC, LSR intensity (safety) and lesion clearance rates (effectiveness) on treatment satisfaction, quality of life and treatment adherence among patients with multiple AKs receiving topical field-directed therapies. METHODS: In this observational, multicentre, longitudinal, cohort study, we included 1136 adult patients with discrete, clinically detectable, visible, multiple (three or more lesions in a 25 cm2 area), Grade I/II AKs, for whom the attending dermatologist has prescribed treatment with a topical field-directed therapy. We matched self-reported data and medical information recorded by dermatologists in standard clinical forms. Patients were followed up at two time points (T1: 8 days; T2: 25-30 days) RESULTS: Most patients were elderly, married, men with poor socio-economic status and multiple lesions of the scalp or face. The majority (n = 961) had a prescription of ingenol mebutate (IMB) and 175 received either diclofenac 3% in hyaluronic acid (DHA) or imiquimod 5% (IMQ). Clearance rate at 1 month was 84%. Most patients felt very supported (n = 819, 73%) and rated dermatologist's explanations very clear (n = 608, 54%). Treatment satisfaction (effectiveness and convenience scales) increased along the follow-up, especially for those on IMB (Δpre-post  = -4.00; other: Δpre-post  = -0.25; interaction P < 0.001). Communication clarity was associated with higher treatment satisfaction scores (ß = 0.4-0.6, P < 0.01) and lower risk of non-adherence among IMB patients (risk difference: 16%, P < 0.01). CONCLUSION: Communication clarity was associated with patient-reported outcomes and adherence beyond AK-related clinical parameters. Our study questions the current episodic approach to AK management and provides the rationale to develop chronic care models fostering patients' engagement and treatment alliance.

Veterinary-focused assessment with sonography for trauma-airway, breathing, circulation, disability and exposure: a prospective observational study in 64 canine trauma patients.

OBJECTIVE: To describe the technique and findings of the 'veterinary focused assessment with sonography for trauma-airway, breathing, circulation, disability and exposure' protocol in dogs suffering from trauma. MATERIALS AND METHODS: Prospective observational study on a new point-of-care ultrasound protocol on 64 dogs suffering from trauma and comparison of findings with radiology. RESULTS: Comparison of the results of this new ultrasound protocol for trauma patients with radiography findings for pneumothorax, pleural effusion, alveolar-interstitial syndrome and abdominal effusion revealed positive agreement of 89, 83, 100 and 87% and negative agreement of 76, 83, 76 and 92%, respectively. Novel findings of the 'veterinary focused assessment with sonography for trauma-airway, breathing, circulation, disability and exposure' exam, which were not previously reported for dogs undergoing focused assessment with sonography for trauma, included alveolar-interstitial syndrome (suggestive of pulmonary contusions), diaphragmatic hernia, retroperitoneal effusion and tracheal injury. Our new technique may also help identify increased intracranial pressure via changes in optic nerve sheath diameter and haemodynamic instability through the evaluation of the caudal vena cava and cardiac function. CLINICAL SIGNIFICANCE: The described ultrasound examination protocol can be rapidly performed on dogs suffering from trauma during resuscitation and it may detect injuries previously undetectable using other veterinary point-of-care ultrasound protocols.

Depression severity and concentration difficulties are independently associated with HRQOL in patients with unipolar depressive disorders.

PURPOSE: Cognitive impairment is a core feature of major depressive disorder (MDD), and dysfunctions in this area strongly contribute to MDD-associated disability. Whether cognitive impairment has an independent clinical course and a unique impact on HRQOL is still debated. We sought to characterize the relationship between depression severity and HRQOL, evaluating the burden of concentration difficulties on HRQOL. METHODS: Six hundred ninety-two patients with unipolar depressive disorders recruited in 19 Italian centers answered a self-administered survey (SF-12 questionnaire, socio-demographic information). A psychiatrist completed a standardized data collection form encompassing a depression severity scale (MADRS) and clinical information. RESULTS: There was a strong graded association between the severity of depressive symptoms and both the physical (ω 2 = 0.13; p < 0.01) and mental (ω 2 = 0.34; p < 0.01) SF-12 domains. Additionally, we observed a strong association between concentration difficulties and all HRQOL outcomes independent of other symptoms of depression and robust to adjustment for possible confounders. CONCLUSIONS: Our data corroborate previous findings suggesting that cognitive impairment is a feature of unipolar depressive disorders partially independent of the severity of other symptoms, and may represent a specific target of therapy with a strong impact on patients' functioning and quality of life.

A Pilot Study Examining a Computer-Based Intervention to Improve Recognition and Understanding of Emotions in Young Children with Communication and Social Deficits.

BACKGROUND: A common social impairment in individuals with ASD is difficulty interpreting and or predicting emotions of others. To date, several interventions targeting teaching emotion recognition and understanding have been utilized both by researchers and practitioners. The results suggest that teaching emotion recognition is possible, but that the results do not generalize to non-instructional contexts. This study sought to replicate earlier findings of a positive impact of teaching emotion recognition using a computer-based intervention and to extend it by testing for generalization on live models in the classroom setting. METHOD: Two boys and one girl, four to eight years in age, educated in self-contained classrooms for students with communication and social skills deficits, participated in this study. A multiple probe across participants design was utilized. Measures of emotion recognition and understanding were assessed at baseline, intervention, and one month post-intervention to determine maintenance effects. Social validity was assessed through parent and teacher questionnaires. RESULTS: All participants showed improvements in measures assessing their recognition of emotions in faces, generalized knowledge to live models, and maintained gains one month post intervention. CONCLUSIONS: These preliminary results are encouraging and should be utilized to inform a group design, in order to test efficacy with a larger population.

A new H2 (+) source: Conceptual study and experimental test of an upgraded version of the VIS-Versatile ion source.

The versatile ion source is an off-resonance microwave discharge ion source which produces a slightly overdense plasma at 2.45 GHz of pumping wave frequency extracting more than 60 mA proton beams and 50 mA He(+) beams. DAEδALUS and IsoDAR experiments require high intensities for H2 (+) beams to be accelerated by high power cyclotrons for neutrinos generation. In order to fulfill the new requirements, a new plasma chamber and injection system has been designed and manufactured for increasing the H2 (+) beam intensity. In this paper the studies for the increasing of the H2 (+)/p ratio and for the design of the new plasma chamber and injection system will be shown and discussed together with the experimental tests carried out at Istituto Nazionale di Fisica Nucleare-Laboratori Nazionali del Sud (INFN-LNS) and at Best Cyclotron Systems test-bench in Vancouver, Canada.

Italian expert consensus for the management of actinic keratosis in immunocompetent patients.

Actinic keratosis (AK) is a common skin disease which can potentially progress to invasive squamous cell carcinoma (iSCC). Given that mortality rates and health-care cost associated with iSCC are substantial, the management of AK represents an important public health issue. Several effective lesion-directed and field-directed treatments are available. Ablative procedures (e.g. cryosurgery, excision, laser ablation, curettage alone or with electrodessication) are considered cost-effective options for solitary lesions. Field-directed therapies (e.g. Ingenol Mebutate, imiquimod, PDT, 5-Fluorouracile, diclofenac 3%, 5-FU + Salicylic acid) can be used over large epidermal surfaces and are directed to treat both individual visible lesions and cancerization fields. In order to provide guidance for management choice in clinical practice, several guidelines concerning the diagnosis and treatment of AK have been published in the past decade. However, the introduction of novel therapeutic options requires continuous updates of recommendations and adaptation to national contexts. The present review summarizes the existing evidence and reports the results of a consensus workshop on the management of AK.

Recent progress in plasma modelling at INFN-LNS.

At Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali del Sud (INFN-LNS), the development of intense ion and proton sources has been supported by a great deal of work on the modelling of microwave generated plasmas for many years. First, a stationary version of the particle-in-cell code was developed for plasma modelling starting from an iterative strategy adopted for the space charge dominated beam transport simulations. Electromagnetic properties of the plasma and full-waves simulations are now affordable for non-homogenous and non-isotropic magnetized plasma via "cold" approximation. The effects of Coulomb collisions on plasma particles dynamics was implemented with the Langevin formalism, instead of simply applying the Spitzer 90° collisions through a Monte Carlo technique. A wide database of different cross sections related to reactions occurring in a hydrogen plasma was implemented. The next step consists of merging such a variety of approaches for retrieving an "as-a-whole" picture of plasma dynamics in ion sources. The preliminary results will be summarized in the paper for a microwave discharge ion source designed for intense and high quality proton beams production, proton source for European Spallation Source project. Even if the realization of a predictive software including the complete processes involved in plasma formation is still rather far, a better comprehension of the source behavior is possible and so the simulations may support the optimization phase.

Experimental investigation of non-linear wave to plasma interaction in a quasi-flat magnetostatic field.

A characterization of wave-to-plasma interaction in a quasi-flat magnetostatic field at 3.75 GHz has been carried out by using a small-wire movable RF antenna, connected to a spectrum analyzer. The coupling between electromagnetic and electrostatic waves leads to a characteristic spectral emission in low frequency range and around the pumping wave frequency. The most relevant results consist in the broadening of the pumping wave spectrum above critical RF power thresholds and in the generation of sidebands of the pumping frequency, with corresponding components in low frequency domain. The non-linearities are accompanied by the generation of overdense plasmas and intense fluxes of X-rays.

Injection of auxiliary electrons for increasing the plasma density in highly charged and high intensity ion sources.

Different electron guns based on cold- or hot-cathode technologies have been developed since 2009 at INFN for operating within ECR plasma chambers as sources of auxiliary electrons, with the aim of boosting the source performances by means of a higher plasma lifetime and density. Their application to microwave discharge ion sources, where plasma is not confined, has required an improvement of the gun design, in order to "screen" the cathode from the plasma particles. Experimental tests carried out on a plasma reactor show a boost of the plasma density, ranging from 10% to 90% when the electron guns are used, as explained by plasma diffusion models.

Electromagnetic analysis of the plasma chamber of an ECR-based charge breeder.

The optimization of the efficiency of an ECR-based charge breeder is a twofold task: efforts must be paid to maximize the capture of the injected 1+ ions by the confined plasma and to produce high charge states to allow post-acceleration at high energies. Both tasks must be faced by studying in detail the electrons heating dynamics, influenced by the microwave-to-plasma coupling mechanism. Numerical simulations are a powerful tools for obtaining quantitative information about the wave-to-plasma interaction process: this paper presents a numerical study of the microwaves propagation and absorption inside the plasma chamber of the PHOENIX charge breeder, which the selective production of exotic species project, under construction at Legnaro National Laboratories, will adopt as charge breeder. Calculations were carried out with a commercial 3D FEM solver: first, all the resonant frequencies were determined by considering a simplified plasma chamber; then, the realistic geometry was taken into account, including a cold plasma model of increasing complexity. The results gave important information about the power absorption and losses and will allow the improvement of the plasma model to be used in a refined step of calculation reproducing the breeding process itself.

A three-dimensional numerical modelling of the PHOENIX-SPES charge breeder based on the Langevin formalism.

A Charge Breeder (CB) is a crucial device of an ISOL facility, allowing post-acceleration of radioactive ions: it accepts an incoming 1+ beam, then multiplying its charge with a highly charged q+ beam as an output. The overall performances of the facility (intensity and attainable final energy) critically depend on the charge breeder optimization. Experimental results collected along the years confirm that the breeding process is still not fully understood and room for improvements still exists: a new numerical approach has been therefore developed and applied to the description of a (85)Rb(1+) beam capture by the plasma of the 14.5 GHz PHOENIX ECR-based CB, installed at the Laboratoire de Physique Subatomique et de Cosmologie (LPSC), and adopted for the Selective Production of Exotic Species project under construction at Laboratori Nazionali di Legnaro. The results of the numerical simulations, obtained implementing a plasma-target model of increasing accuracy and different values for the plasma potential, will be described along the paper: results very well agree with the theoretical predictions and with the experimental results obtained on the LPSC test bench.

Bloating is associated with worse quality of life, treatment satisfaction, and treatment responsiveness among patients with constipation-predominant irritable bowel syndrome and functional constipation.

BACKGROUND: The management of bloating is unclear and its relationship with patients' well-being and treatment satisfaction independent of other abdominal symptoms is uncharacterized. We evaluated the association of bloating with patient-reported outcomes. METHODS: Thirty-nine centers for functional gastrointestinal disorders joined the laxative inadequate relief survey. We enrolled 2203 consecutive outpatients with functional constipation (FC) or constipation-predominant irritable bowel syndrome (IBS-C) in two cross-sectional waves. Both wave 1 and 2 included the SF-12, the patient assessment of constipation-symptoms (PAC-SYM), and the treatment satisfaction questionnaire for medication (TSQM-2). Wave 2 only included a global rating of change (GRC) scale to assess patients' assessment of efficacy concerning treatment switches occurred in the 3 months prior to the interview. Bloating in the abdomen was defined on the basis of PAC-SYM item 3. KEY RESULTS: The average age was 50.1 years (SD, 16.7) and 82.1% of patients were women. The prevalence of bloating was 91.6% (n = 1970). Bloating was associated with SF-12 Physical Composite Score (p < 0.01), SF-12 Mental Composite Score (p < 0.01), GRC (p < 0.01), Satisfaction with treatment effectiveness (p < 0.01), convenience of administration (p < 0.01), and side effects (p < 0.01) after adjustment for possible confounders. CONCLUSIONS & INFERENCES: Our data suggest that patients regard bloating as a key element in assessing clinical changes and treatments' efficacy as this symptom exerts a strong influence on patient-reported outcomes independent of possible confounders and other symptoms of constipation. Our data provide the rationale to investigate the efficacy and tolerability of new treatments specifically addressing this important, yet disregarded, patients' complain.