Serology of Lupus Erythematosus: Correlation between Immunopathological Features and Clinical Aspects

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the aberrant production of a broad and heterogenous group of autoantibodies. Even though the presence of autoantibodies in SLE has been known, for more than 60 years, still nowadays a great effort is being made to understand the pathogenetic, diagnostic, and prognostic meaning of such autoantibodies. Antibodies to ds-DNA are useful for the diagnosis of SLE, to monitor the disease activity, and correlate with renal and central nervous involvements. Anti-Sm antibodies are highly specific for SLE. Anti-nucleosome antibodies are an excellent marker for SLE and good predictors of flares in quiescent lupus. Anti-histone antibodies characterize drug-induced lupus, while anti-SSA/Ro and anti-SSB/La antibodies are associated with neonatal lupus erythematosus and photosensitivity. Anti-ribosomal P antibodies play a role in neuropsychiatric lupus, but their association with clinical manifestations is still unclear. Anti-phospholipid antibodies are associated with the anti-phospholipid syndrome, cerebral vascular disease, and neuropsychiatric lupus. Anti-C1q antibodies amplify glomerular injury, and the elevation of their titers may predict renal flares. Anti-RNP antibodies are a marker of Sharp’s syndrome but can be found in SLE as well. Anti-PCNA antibodies are present in 5–10% of SLE patients especially those with arthritis and hypocomplementemia

Martinetti, Agostino e l'Abbé Coignard

L'apertura alla dimensione religiosa nel "Kant" di Martinetti e il percorso teorico di Dal Pra fra trascendenza e immanenza. Un ipotetico punto di incontro sul terreno della prassi e della scelta etica

Variable RBE in proton therapy: comparison of different model predictions and their influence on clinical-like scenarios

Background: In proton radiation therapy a constant relative biological effectiveness (RBE) of 1.1 is usually assumed. However, biological experiments have evidenced RBE dependencies on dose level, proton linear energy transfer (LET) and tissue type. This work compares the predictions of three of the main radio-biological models proposed in the literature by Carabe-Fernandez, Wedenberg, Scholz and coworkers. Methods: Using the chosen models, a spread-out Bragg peak (SOBP) as well as two exemplary clinical cases (single field and two fields) for cranial proton irradiation, all delivered with state-of-the-art pencil-beam scanning, have been analyzed in terms of absorbed dose, dose-averaged LET (LETD), RBE-weighted dose (D-RBE) and biological range shift distributions. Results: In the systematic comparison of RBE predictions by the three models we could show different levels of agreement depending on (alpha/beta)(x) and LET values. The SOBP study emphasizes the variation of LETD and RBE not only as a function of depth but also of lateral distance from the central beam axis. Application to clinical-like scenario shows consistent discrepancies from the values obtained for a constant RBE of 1.1, when using a variable RBE scheme for proton irradiation in tissues with low (alpha/beta)(x), regardless of the model. Biological range shifts of 0.6-2.4 mm (for high (alpha/beta)(x)) and 3.0 -5.4 mm (for low (alpha/beta)(x)) were found from the fall-off analysis of individual profiles of RBE-weighted fraction dose along the beam penetration depth. Conclusions: Although more experimental evidence is needed to validate the accuracy of the investigated models and their input parameters, their consistent trend suggests that their main RBE dependencies (dose, LET and (alpha/beta)(x)) should be included in treatment planning systems. In particular, our results suggest that simpler models based on the linear-quadratic formalism and LETD might already be sufficient to reproduce important RBE dependencies for re-evaluation of plans optimized with the current RBE = 1.1 approximation. This approach would be a first step forward to consider RBE variations in proton therapy, thus enabling a more robust choice of biological dose delivery. The latter could in turn impact clinical outcome, especially in terms of reduced toxicities for tumors adjacent to organs at risk

MIS-C Treatment: Is IVIG Always Necessary?

Background: MIS-C is a potentially severe inflammatory syndrome associated with SARS-CoV-2 exposure. Intravenous immunoglobulin (IVIG) is considered the first-tier therapy, but it implies infusion of large fluid volumes that may worsen cardiac function. Patients and Methods: Since April 2020, we have developed a treatment protocol that avoids the infusion of IVIG as first-line therapy in the early phase of MIS-C. In this study, we retrospectively analyzed a cohort of consecutive patients treated according to this protocol between 01/04/2020 and 01/04/2021. Results: In the last year, 31 patients have been treated according to the protocol: 25 with high-dose pulse MP (10 mg/kg) and 6 with 2 mg/kg. 67.7% of the patients responded to the initial treatment, while the others needed a step-up, either with Anakinra (25.8%) or with MP dose increase (6.5%). IVIG was administered in four patients. Overall, only one patient (3.2%) needed ICU admission and inotropic support; one patient developed a small coronary artery aneurysm. Conclusions: Timely start of MP therapy and careful fluid management might improve the outcomes of MIS-C patients

First diagnosis of multisystem inflammatory syndrome in children (MIS-C): an analysis of PoCUS findings in the ED

Children with multisystem inflammatory syndrome (MIS-C) tend to develop a clinical condition of fluid overload due both to contractile cardiac pump deficit and to endotheliitis with subsequent capillary leak syndrome. In this context, the ability of point-of-care ultrasound (PoCUS) to simultaneously explore multiple systems and detect polyserositis could promote adequate therapeutic management of fluid balance. We describe the PoCUS findings in a case-series of MIS-C patients admitted to the Emergency Department. At admission 10/11 patients showed satisfactory clinical condition without signs and symptoms suggestive for cardiovascular impairment/shock, but PoCUS showed pathological findings in 11/11 (100%). In particular, according to Rapid Ultrasound in SHock (RUSH) protocol, cardiac hypokinesis was detected in 5/11 (45%) and inferior vena cava dilatation in 3/11 (27%). Peritoneal fluid was reported in 6/11 cases (54%). Lung ultrasound (LUS) evaluation revealed an interstitial syndrome in 11/11 (100%), mainly localized in posterior basal lung segments. We suggest PoCUS as a useful tool in the first evaluation of children with suspected MIS-C for the initial therapeutic management and the following monitoring of possible cardiovascular deterioration

Peripheral artery disease and blood pressure profile abnormalities in hemodialysis patients

Patients undergoing chronic hemodialysis (HD) are at increased risk for peripheral artery disease (PAD). Both ankle-brachial index (ABI) and ambulatory blood pressure monitoring (ABPM) in the interdialytic period have been shown to be strong predictors of all-cause mortality

SCN1A-deficient excitatory neuronal networks display mutation-specific phenotypes

Dravet syndrome is a severe epileptic encephalopathy, characterized by (febrile) seizures, behavioural problems and developmental delay. Eighty per cent of patients with Dravet syndrome have a mutation in SCN1A, encoding Nav1.1. Milder clinical phenotypes, such as GEFS+ (generalized epilepsy with febrile seizures plus), can also arise from SCN1A mutations. Predicting the clinical phenotypic outcome based on the type of mutation remains challenging, even when the same mutation is inherited within one family. This clinical and genetic heterogeneity adds to the difficulties of predicting disease progression and tailoring the prescription of anti-seizure medication. Understanding the neuropathology of different SCN1A mutations may help to predict the expected clinical phenotypes and inform the selection of best-fit treatments. Initially, the loss of Na+-current in inhibitory neurons was recognized specifically to result in disinhibition and consequently seizure generation. However, the extent to which excitatory neurons contribute to the pathophysiology is currently debated and might depend on the patient clinical phenotype or the specific SCN1A mutation. To examine the genotype-phenotype correlations of SCN1A mutations in relation to excitatory neurons, we investigated a panel of patient-derived excitatory neuronal networks differentiated on multi-electrode arrays. We included patients with different clinical phenotypes, harbouring various SCN1A mutations, along with a family in which the same mutation led to febrile seizures, GEFS+ or Dravet syndrome. We hitherto describe a previously unidentified functional excitatory neuronal network phenotype in the context of epilepsy, which corresponds to seizurogenic network prediction patterns elicited by proconvulsive compounds. We found that excitatory neuronal networks were affected differently, depending on the type of SCN1A mutation, but did not segregate according to clinical severity. Specifically, loss-of-function mutations could be distinguished from missense mutations, and mutations in the pore domain could be distinguished from mutations in the voltage sensing domain. Furthermore, all patients showed aggravated neuronal network responses at febrile temperatures compared with controls. Finally, retrospective drug screening revealed that anti-seizure medication affected GEFS+ patient- but not Dravet patient-derived neuronal networks in a patient-specific and clinically relevant manner. In conclusion, our results indicate a mutation-specific excitatory neuronal network phenotype, which recapitulates the foremost clinically relevant features, providing future opportunities for precision therapies.</p

ChAMBRe: studi su bio-aerosol in camera di simulazione atmosferica

Nella Sezione di Genova dell\u2019Istituto Nazionale di Fisica Nucleare \ue8 stata recentemente installata, in collaborazione con il Laboratorio di Fisica Ambientale del Dipartimento di Fisica dell\u2019Universit\ue0 di Genova, ChAMBRe (Chamber for Aerosol Modelling and Bio-aerosol Research), la prima Camera di simulazione atmosferica specificatamente concepita per studiare la componente biologica dell\u2019aerosol atmosferico. Presso la camera di simulazione atmosferica CESAM (Cr\ue9teil, Francia) sono sati effettuati alcuni esperimenti pilota recentemente pubblicati [1], che sono stati lo spunto per la costruzione di una struttura dedicata allo studio del comportamento dei pi\uf9 comuni agenti patogeni presenti in atmosfera sotto forma di bioaerosol e in particolare dei meccanismi che controllano le interazioni tra questi e le altre componenti dell\u2019aerosol e pi\uf9 in generale dell\u2019atmosfera. L\u2019attivit\ue0 di ricerca a ChAMBRe si concentrer\ue0 sull\u2019indagine del comportamento del bio-aerosol in differenti condizioni atmosferiche e in presenza di tipici inquinanti antropici (come il monossido di carbonio, gli ossidi di azoto, etc.) che possono influenzare la vitalit\ue0, la morfologia e la dispersione dei batteri in atmosfera. Come primo passo \ue8 necessario innanzitutto mettere a punto un protocollo che garantisca la riproducibilit\ue0 degli esperimenti in una struttura complessa come ChAMBRe. Ci si \ue8 quindi concentrati su aspetti cruciali quali: crescita in vitro e successiva iniezione in camera di una data concentrazione di batteri, seguita da una fase di estrazione, campionamento e misura della vita media all\u2019interno della camera. Gli esperimenti sono volti anche ad identificare eventuali condizioni di stress ambientali e meccaniche per i microrganismi e la loro risposta come singoli individui e come colonie. Sono stati eseguiti esperimenti su due tipologie di ceppi batterici frequentemente utilizzati come organismi modello: il Bacillus subtilis e l\u2019Escherichia coli, appartenenti rispettivamente al gruppo dei Gram-positivi e dei Gram-negativi. I risultati e il protocollo sperimentale messo a punto verranno presentati a PM2018

Road traffic pollution and childhood leukemia: a nationwide case-control study in Italy

Background The association of childhood leukemia with traffic pollution was considered in a number of studies from 1989 onwards, with results not entirely consistent and little information regarding subtypes. Aim of the study We used the data of the Italian SETIL case-control on childhood leukemia to explore the risk by leukemia subtypes associated to exposure to vehicular traffic. Methods We included in the analyses 648 cases of childhood leukemia (565 Acute lymphoblastic–ALL and 80 Acute non lymphoblastic-AnLL) and 980 controls. Information on traffic exposure was collected from questionnaire interviews and from the geocoding of house addresses, for all periods of life of the children. Results We observed an increase in risk for AnLL, and at a lower extent for ALL, with indicators of exposure to traffic pollutants. In particular, the risk was associated to the report of closeness of the house to traffic lights and to the passage of trucks (OR: 1.76; 95% CI 1.03–3.01 for ALL and 6.35; 95% CI 2.59–15.6 for AnLL). The association was shown also in the analyses limited to AML and in the stratified analyses and in respect to the house in different period of life. Conclusions Results from the SETIL study provide some support to the association of traffic related exposure and risk for AnLL, but at a lesser extent for ALL. Our conclusion highlights the need for leukemia type specific analyses in future studies. Results support the need of controlling exposure from traffic pollution, even if knowledge is not complete