Search

Monica Bocchia,1 Angelo Michele Carella,2 Antonino Mulè,3 Lorenzo Rizzo,4 Mauro Turrini,5 Maria Chiara Abbenante,2 Roberto Cairoli,4 Valeria Calafiore,3 Marzia Defina,1 Angelo Gardellini,5 Giovanni Luzi,6 Caterina Patti,3 Maria Beatrice Pinazzi,6 Marta Riva,4 Giovanni Rossi,2 Vincenzo Sammartano,1 Luigi Rigacci6 1Hematology Unit, Azienda Ospedaliera Universitaria Senese, University of Siena, Siena, Italy; 2Division of Hematology with Hematologic Intensive Care Unit and Cellular Therapies, Department of Medical Science, Fondazione IRCCS Casa Sollievo Della Sofferenza, Foggia, Italy; 3UOC Hematology and Oncology, Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy; 4Department of Haematology, Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; 5Division of Hematology, Valduce Hospital, Como, Italy; 6UOC Hematology and Stem Cell Transplant Unit, Ospedale S, Camillo, Rome, ItalyCorrespondence: Angelo Michele Carella, Division of Hematology with Hematologic Intensive Care Unit and Cellular Therapies, Department of Medical Science, Fondazione IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini, San Giovanni Rotondo, Foggia, 71013, Italy, Tel +390882410054, Fax +390882410322, Email am.carella@operapadrepio.itAbstract: Acute myeloid leukemia is a malignant disorder of the bone marrow, characterized by differentiation, clonal expansion, and uncontrolled proliferation of malignant myeloid progenitor cells and by several molecular and genetic abnormalities. A mutation of FMS-like tyrosine kinase 3 gene can be observed in about one-third of cases of acute myeloid leukemia. Two FLT3 inhibitors are actually approved for FLT3 mutated acute myeloid leukemia: midostaurin, a multikinase first generation inhibitor with lower affinity for FLT3 binding, and gilteritinib fumarate, a potent second-generation inhibitor of both FLT3-ITD and TKD. Gilteritinib is a new effective and well-tolerated drug for patients with relapsing or refractory FLT3-positive acute myeloid leukemia. Thanks to its efficacy, low toxicity, its good manageability (oral formulation), this drug is suitable for all the patients, including elderly frail patient with concomitant therapies or pre-existing or underlying diseases, and can be used also in the outpatient setting, reducing risks and costs related to the hospitalization. We report and discuss seven cases of different patients with FLT3 positive acute myeloid leukemia successfully managed with gilteritinib in the real clinical practice.Keywords: acute myeloid leukemia, FLT3, midostaurin, gilteritinib

Additional file 4. Supplemental materials and methods.

Additional file 2.

Additional file 3.

Additional file 1.

Emergency medicine is a new discipline that is rapidly developing and spreading in medical practice. The central themes of emergency medicine are resuscitation, laboratory and diagnostic imaging. In the emergency department, different parameters can be associated with a prolonged Length of Stay (LOS) as, for example; the protact use of computed tomography (TAC), radiology techniques, the need for advice from external consultants (1). To improve the efficiency of the emergency department and the assessment effectiveness of the state of healthy patient, it is important to identify the factors that affect the LOS (2).This work was based on the evaluation of the impact of demographic factors, clinical information and diagnostic techniques on the LOS in emergency medicine (LOS-ED). The dataset was carried out at the Emergency Medicine Unit of the hospital “San Giovanni di Dio e Ruggi d’Aragona” of Salerno. Multiple Linear Regression model was optimized considering the hospital stay after diagnostic procedures (dLOS) as dependent variable.

BACKGROUND: To highlight clinical practice among referral (Hub, HH) or satellite (Spoke, SH) hospitals Vascular Surgery Units (VSUs) in Lombardy, during the COVID-19 pandemic "phase 1" period (March 8 - May 3, 2020). METHODS: The Vascular Surgery Group of Regione Lombardia Register, a real-word, multicenter, retrospective register was interrogated. All patients admitted with vascular disease were included. Patients' data on demographics, COVID-19 positivity, comorbidities and outcomes were extrapolated. Two cohorts were obtained: patients admitted to HH or SH. Primary endpoint was 30- day mortality rate. Secondary outcomes were 30-day complications and amputation (in case of peripheral artery disease [PAD]) rates. Univariate and multivariate analysis were used to compare HH and SH groups and predictors of poor outcomes. RESULTS: During the study period, 659 vascular patients in 4 HH and 27 SH were analyzed. Among these, 321 (48.7%) were admitted to a HH. No difference in COVID-19 positive patients was described (21.7% in HH vs 15.9% in SH; p=.058). After 30 days from intervention, HH and SH experienced similar mortality and no-intervention-related complication rate (12.1% vs 10.0%; p=.427 and 10.3% vs 8.3%; p=.377, respectively). Conversely, in HH postoperative complications were higher (23.4% vs 16.9%, p=.038) and amputations in patients treated for PAD were lower (10.8% vs 26.8%; p

Getting others to do things is a central part of social interaction in any human society. Language is our main tool for this purpose. In this book, we show that sequences of interaction in which one person’s behaviour solicits or occasions another’s assistance or collaboration share common structural properties that provide a basis for the systematic comparison of this domain across languages. The goal of this comparison is to uncover similarities and differences in how language and other conduct are used in carrying out social action around the world, including different kinds of requests, orders, suggestions, and other actions brought together under the rubric of recruitment.

Additional file 9. Meristic data of Barbus plebejus (N = 153) and Barbus tyberinus (N = 168) from [28, 33, 34] and Barbus oscensis (i.e., the B. tyberinus TSAAC clade; N = 6) from original counts. Vertical lines: observed range; dithered boxes and horizontal lines: usual values. Characters with no evident variability between subspecies are not shown.

Additional file 3. GenBank Accession Numbers and geographical abundancies of sequences used for single-marker minimum spanning network computations (see Additional file 6). TL, Tuscany-Latium district; PV, Padano-Venetian district; NAAC, northernmost-Adriatic part of Apulia-Campania district; TSAAC, Tyrrhenian and southernmost-Adriatic parts of Apulia-Campania district; DAN, Danubian district; AccNum, GenBank Accession Number.

Leuciscus is a genus of fish belonging to subfamily Leuciscinae. While, it is widely distributed throughout Eurasia, our perception of the phylogenetic relationships among its members is mainly based on morphological characters. In this study, two mitochondrial (CYTB and COX1) and one nuclear (RAG1) genomic markers were used in order to assess the taxonomic relationships between two Iranian Leuciscus morpho-species. Analysis of the combined dataset using Maximum Likelihood (ML) and Bayesian Inference (BI) resulted in well-resolved trees, where most clades were supported by high statistical values. The trees revealed two clades corresponding with the Caspian Asp, Leuciscus aspius, and the Mesopotamian Asp, L. vorax. The mean intraspecific and interspecific genetic distance between Leuciscus species was 0.5% and 10.6%, respectively. The genetic distance between L. aspius sequences of Iran and Europe was 1.1% and the genetic distance between L. vorax sequences from Iran and those of Turkey and Syria was 0.8%. This confirmed that the morpho-species Leuciscus from the Caspian basin belongs to L. aspius, while those from the Tigris basin belong to L. vorax. Due to very small genetic distances between some Leuciscus members, specific species delimitation analyses are required to clarify genus taxonomy throughout its distribution range.

Additional file 8. Meristic data of Barbus plebejus and B. tyberinus from [28, 33, 34] and morphometric and meristic data of B. oscensis (i.e., the B. tyberinus TSAAC clade).

Additional file 4. Dataset, taxonomy, river/watershed location, sampling coordinates in EPSG 32632 reference systems and GenBank Accession Numbers.

Additional file 6. Tests for chance occurrence of reciprocal monophyly. All analyses were carried out using the Species Delimitation Plugin of Geneious Prime® 2021.0.3.

Additional file 7. Single-marker minimum spanning networks computed from sequences and geographical abundancies listed in S4. a, cytb; b, D-loop. Asterisks mark samples that was not possible to unambiguously assign to an ichthyogeographical district (see also Fig. 4).

Additional file 1. Sampling sites distribution, along with coordinates in EPSG 32632 reference systems.

Additional file 10. Tukey post-hoc test results. The table lists the Q value; the p-value is shown in parentheses. ***, p

Additional file 2. Dichotomous key for barbels of Apennine Peninsula and Adriatic basin of Slovenia and Croatia [15].

Additional file 5. Original phylogenetic trees in NEXUS format as computed by IQ-TREE, MrBayes, and RAxML, respectively. Each OTU is labeled with the resulting clade (see Fig. 2) and with GenBank Accession Numbers (Additional file 4).

The production of phosgene typically involves the gas phase reaction between carbon monoxide (CO) and dichlorine (Cl2) in the presence of an activated carbon catalyst. The first stage of the study investigated the kinetics of phosgene formation over a high surface area carbon catalyst. This included determining a rate law and an activation energy for the reaction. A reaction mechanism is proposed based on the experimental observations.

This work proposes an alternative approach to the so-called lattice of embedded subsets, which is included in the product of the subset and partition lattices of a finite set, and whose elements are pairs consisting of a subset and a partition where the former is a block of the latter. The lattice structure proposed in a recent contribution relies on ad-hoc definitions of both the join operator and the bottom element, while also including join-irreducible elements distinct from atoms. Conversely, here embedded subsets obtain through a closure operator defined over the product of the subset and partition lattices, where elements are generic pairs of a subset and a partition. Those such pairs that coincide with their closure are precisely embedded subsets, and since the Steinitz exchange axiom is also satisfied, what results is a geometric (hence atomic) lattice given by a simple matroid (or combinatorial geometry) included in the product of the subset and partition lattices (as the partition lattice itself is the polygon matroid defined on the edges of a complete graph). By focusing on its M\"obius function, this geometric lattice of embedded subsets of a n-set is shown to be isomorphic to the lattice of partitions of a n+1-set.

Respiratory Syncytial Virus (RSV) is a frequent cause of hospital admission in young children and high risk babies such as premature newborns, or babies with underlying cardiac or pulmonary disease, or immunodeficiency. Outbreaks occur most frequently in the cold season in areas with temperate and Mediterranean climates. Aim of the "Osservatorio VRS" Study was to describe the time-related pattern of RSV epidemics in Italy, across four consecutive epidemics, from 2000 to 2004. Nasal specimens for RSV detection were obtained and tested by an immunoenzymatic test. A total of 2110 children were tested for RSV determination, the rate of children with RSV infection was 21%, and that of children hospitalized for RSV disease was 49%. Considering the whole study period, the RSV epidemics started in October-November and ended in May, showing a peak incidence in February, with a median of 28.1% and a maximum of 48.9%. Analysis of monthly distribution of each year of the study showed a biennial trend for an earlier appearance. A different epidemiological pattern of the infection was observed among the three national areas. In conclusion, even though the mechanism governing RSV infection periodicity remains unknown, its awareness in the absence of an RSV surveillance system as in Italy, may be useful for scheduling RSV prophylaxis and for hospital resource management.

The design and construction of two experimental platforms for the testing of heterogeneous catalysts are described. The first is intended for a vapour phase dimerisation process over a solid catalyst. Issues connected with refinement of that experimental arrangement are described and an operational specification defined. No catalyst testing is reported for this arrangement. The second apparatus is designed to explore carbonyl chloride (phosgene) synthesis from the reaction of CO and Cl2 over high surface area carbon catalysts. After the experimental configuration of the phosgene test facility has been described, a series of reaction test data using a Donau Supersorbon K40 catalyst is presented. Steady state phosgene production was established and is associated with an activation energy of 28 kJ mol-1. Van’t Hoff plots were adopted to obtain the rate law for this reaction and a reaction scheme is proposed. Overall this study is intended to provide training in the design, construction and testing of heterogeneous catalyst test apparatus. Further, the phosgene synthesis measurements are intended to provide insight into an important application of process chemistry relevant to an isocyanate production chain.

L'oggetto di ricerca della presente tesi di dottorato concerne la delicata questione della responsabilità del concorrente rispetto ad un reato diverso da quello originariamente voluto, cioè la responsabilità del “concorrente anomalo” di cui all'articolo 116 c.p. Secondo tale disposizione, infatti – espressamente rubricata << reato diverso da quello voluto da taluno dei concorrenti >> –, << qualora il reato commesso sia diverso da quello voluto da taluno dei concorrenti, anche questi ne risponde, se l'evento è conseguenza della sua azione od omissione >>. Classico è l'esempio dei due concorrenti che originariamente si organizzano per commettere un furto in abitazione (ritenuta al momento disabitata), ma dove poi uno dei due, per fronteggiare le resistenze dell'inaspettata vittima, commette in concreto una rapina. In questo caso, quindi, risponderà della rapina anche il concorrente che voleva realizzare esclusivamente il furto e che si è limitato a fare da “palo” rimanendo fuori dall'abitazione? Oppure sarà considerato responsabile della rapina solo il concorrente esecutore materiale della stessa? La risposta a questi quesiti sembra essere dettata esplicitamente nella lettera dell'articolo 116 c.p., secondo cui, come poc'anzi ricordato, del reato diverso (o più grave) effettivamente commesso da uno dei concorrenti risponde anche il concorrente che non lo ha voluto, ovvero il cosiddetto “concorrente anomalo”. Tuttavia, contrariamente a quanto appare prima facie, l'individuazione concreta degli elementi costitutivi – oggettivi e soggettivi – di tale ipotesi concorsuale è tutt'altro che chiara, soprattutto alla luce dei principi costituzionali che devono informare tutto il diritto penale. In particolare, il nodo problematico non ancora risolto in maniera univoca, né in dottrina e in giurisprudenza, è quello della natura giuridica della responsabilità del concorrente anomalo. Secondo alcuni, infatti, quest'ultima è una chiara ipotesi di responsabilità oggettiva, in cui manca del tutto l'accertamento dell'elemento soggettivo della fattispecie; secondo altri, invece, è una tipica ipotesi di responsabilità dolosa; per la giurisprudenza dominante, viceversa, seguita anche da una cospicua parte della dottrina, il concorso anomalo rappresenta una particolare forma di responsabilità colposa, dove però l'elemento della colpa viene sostituito in concreto dal requisito della “prevedibilità”. A tale proposito, in questo studio si cerca di evidenziare che, nonostante le innumerevoli interpretazioni proposte sia a livello accademico sia a livello giurisprudenziale, la disposizione dell'articolo 116 c.p. risulta tuttora in evidente contrasto con i fondamentali principi costituzionali su cui si basa l'attuale diritto penale del fatto, tra cui quelli della personalità della responsabilità penale (art. 27, comma 1, Cost.), della tipicità della fattispecie (art. 25, comma 2, Cost.), della funzione rieducativa della pena, nonché della proporzione della stessa rispetto al fatto concreto (artt, 27, comma 3, e 3 Cost.). Tuttavia, prima di analizzare approfonditamente la questione della natura giuridica della responsabilità del concorrente anomalo, questo lavoro si impegna di inquadrare in via sistematica la fattispecie dell'articolo 116 c.p. all'interno del contesto della disciplina del concorso di persone nel reato di cui agli articoli 110 e seguenti c.p. Difatti, solo partendo da una preliminare analisi della disciplina generale del concorso eventuale di persone nel reato, con una descrizione di tutti i suoi elementi costitutivi (di natura oggettiva e di natura soggettiva), si possono poi individuare le differenze e le eccezioni che alla stessa disciplina generale vengono poste con la peculiare disciplina del concorso anomalo. Di conseguenza, in primo luogo, la presente ricerca di dottorato si focalizza sulla disciplina generale del concorso di persone nel reato, nonché sulle opzioni dogmatiche e di politica criminale che con essa il legislatore del 1930 ha voluto soddisfare. Nel dettaglio, in via preliminare, si pone l'attenzione sulle diversità dei due possibili modelli di disciplina del concorso di persone nel reato, quello differenziato e quello unitario, sottolineando le ragioni che hanno condotto il legislatore dell'epoca a scegliere quest'ultimo modello. Inevitabilmente, quindi, si passano in rassegna i requisiti strutturali dell'ordinario concorso di persone nel reato, cosiddetto concorso eventuale di persone o fattispecie plurisoggettiva eventuale, per poi passare alla disciplina delle circostanze, nonché a quella particolare ipotesi di concorso di persone nel reato denominata cooperazione nel delitto colposo. Dopo aver fatto questa prima disamina sulla disciplina generale del concorso di persone, la trattazione si sposta funditus sull'argomento della responsabilità del concorrente anomalo, delineando tutti gli orientamenti interpretativi che si sono susseguiti nel tempo, a partire dall'entrata in vigore del codice penale Rocco del 1930. E precisamente, per quanto concerne la natura di tale responsabilità, vengono analizzati i lavori preparatori del codice penale per individuare se effettivamente la ratio legis era effettivamente quella di inserire nel concorso di persone una chiara ipotesi di responsabilità oggettiva, basata esclusivamente sul nesso di causalità materiale. Tuttavia, proprio dall'analisi dei lavori preparatori si percepisce che anche all'epoca della stesura del codice penale non vi era unanimità di vedute sulla natura della responsabilità del concorrente anomalo, anzi, nella relazione al progetto emergeva già in nuce un orientamento che riteneva sussistente l'elemento psicologico doloso nella fattispecie dell'articolo 116 c.p. Nonostante questa originaria incertezza dei lavori preparatori, successivamente in dottrina si è prevalentemente sostenuto che la responsabilità del concorrente anomalo rappresentasse un'ipotesi di responsabilità oggettiva, ove non occorre l'accertamento dell'elemento soggettivo, bensì è sufficiente il mero rapporto di causalità materiale. Questa interpretazione, però, se chiaramente in linea con il regime autoritario dell'epoca, non è più compatibile con l'odierno diritto penale costituzionalmente orientato, dove per la responsabilità di un fatto-reato necessita che questo sia attribuito all'individuo – come affermato anche dalle storiche sentenze 364 e 1085 del 1988 della Corte Cost. – sia dal punto di vista oggettivo che dal punto di vista soggettivo. In altri termini, sulla base del principio della personalità della responsabilità penale, una persona può essere ritenuta responsabile di un fatto-reato solo quando questo è ricollegabile alla stessa sia dal punto di vista del rapporto di causalità materiale che dal punto di vista dell'elemento psicologico, doloso o colposo. Così facendo, dunque, necessitano sempre gli elementi oggettivi e soggettivi della fattispecie, risultando incompatibili con l'attuale assetto costituzionale, in particolare con il principio della personalità responsabilità penale di cui all'art. 27, comma 1, Cost., tutte le ipotesi di mera responsabilità oggettiva, dove è sufficiente, per la punibilità, l'accertamento del solo nesso di causalità materiale. Orbene, per risolvere la questione della compatibilità costituzionale dell'art. 116 c.p., il cui testo sembrerebbe propendere proprio per la sufficienza dell'accertamento del solo rapporto causale, la Corte Cost. è intervenuta con una sentenza interpretativa di rigetto, la n. 42 del 1965, con la quale si esclude l'illegittimità costituzionale dell'attuale disciplina del concorso anomalo. Pertanto, per comprendere le ragioni del rigetto, prima si è analizzata la pronuncia della Consulta, per poi evidenziarne i punti critici che dalla stessa sono derivati. In sostanza, accanto al nesso di causalità materiale, la Corte ha affermato la necessaria presenza di un nesso di “causalità psichica” che sia in grado di rappresentare un indice di colpevolezza. Quest'ultimo, in particolare, viene ravvisato dalla Consulta nella prevedibilità dell'evento diverso e non voluto dal concorrente. Secondo le parole della Corte, l'evento diverso e più grave deve essere uno “sviluppo logicamente prevedibile” di quello voluto. Pertanto, solo se si accerta tale prevedibilità del fatto diverso e più grave si può affermare la responsabilità del concorrente ex art. 116 c.p. Con tale interpretazione adeguatrice – o correttiva –, mutuata dalla prevalente giurisprudenza di legittimità, la Corte costituzionale nega che l’art. 116 c.p. costituisca un’ipotesi di responsabilità oggettiva, come tale contraria all’art. 27, comma 1, Cost. Da questa sentenza, però, è scaturito un acceso dibattito sulla natura del requisito della prevedibilità, che può essere intesa in astratto o in concreto. Tuttavia, come emerge nel lavoro di ricerca, nonostante la teoria della prevedibilità in concreto sia ormai quella seguita dalla giurisprudenza attualmente prevalente, essa non è in grado di eliminare i dubbi di legittimità costituzionale della norma in esame. Ciò detto, rilevati gli orientamenti giurisprudenziali sul punto, si passano ad analizzare le diverse interpretazioni dottrinarie sull'elemento soggettivo nel concorso anomalo. Infatti, ancor prima della ricordata sentenza della Corte Cost., n. 42 del 1965, la dottrina ha cercato di ricostruire ab origine un elemento psicologico nella fattispecie dell'art. 116 c.p., negando così la sua natura di responsabilità oggettiva. Originariamente, infatti, non è mancato chi ha accolto la tesi della responsabilità a titolo di dolo. E tale orientamento è stato sostenuto facendo riferimento a diverse argomentazioni. Così come non è mancato chi ha sostenuto la natura sostanzialmente colposa del concorso anomalo. Invero, con la sentenza adeguatrice della Corte Costituzionale, come già detto, si introduce nell'art. 116 c.p. l'elemento della “prevedibilità”, classico presupposto dell'imputazione soggettiva a titolo di colpa. Tuttavia, come afferma autorevole dottrina, si tratta di una colpa sui generis, perché manca un suo elemento caratterizzante: non si richiede, infatti, per la punibilità ex art. 116 c.p., la violazione di una regola oggettiva di diligenza diretta ad evitare quel determinato fatto concretamente realizzato. Ed a questa obiezione non si può replicare affermando che la violazione del dovere obiettivo di diligenza sarebbe rappresentato dall'imprudenza di essersi affidato, per la realizzazione del proposito criminoso, alla condotta altrui, come tale non controllabile. In tal modo, infatti, si crea solo una presunzione di colpa in capo ad ogni compartecipe che concorre con altri per commettere un reato, anche se poi in concreto viene realizzato un reato diverso e non voluto. In ogni caso, seppure si volesse accogliere la tesi della responsabilità a titolo di colpa, è evidente che saremmo di fronte ad una violazione del principio generale dell'art. 42, co. 2, c.p. Quest'ultimo, infatti, stabilisce che si può essere puniti a titolo di colpa solo se il reato è espressamente previsto dalla legge come colposo, cosa che invece non accade nell'art. 116 c.p. Di conseguenza, resta l'anomalia della responsabilità racchiusa nella norma in commento. Da un lato, perché non c'è una concreta violazione di un regola obiettiva di diligenza – a meno che non si voglia accogliere la tesi della presunzione di colpa –; dall'altro, perché non è espressamente prevista dalla norma la punibilità a titolo di colpa del concorrente anomalo. È evidente, quindi, che in tutte le ricostruzioni fornite non vi è altro che una mera presunzione dell'elemento psicologico, in concreto mai accertato. Peraltro, una responsabilità “apparentemente colposa”, data la “prevedibilità” in concreto dell'evento diverso, viene punita a titolo di dolo, con evidente sproporzione della pena rispetto al grado di colpevolezza. Da queste semplici constatazioni sembra evidente come il problema della compatibilità dell'art. 116 c.p. con il principio della personalità della responsabilità penale – di cui all'art. 27 Cost. – è tutt'altro che risolto. Anzi, se la colpevolezza è il limite normativo oltre il quale non può andare la sanzione penale, applicare una pena a titolo di dolo per un fatto strutturalmente colposo – ma non previsto come tale dalla legge – rappresenta una violazione del su menzionato principio, oltre che del principio di legalità di cui all'art. 25, comma 2, Cost. Precisamente, si applicherebbe una sanzione – prevista per il reato doloso – sproporzionata rispetto all'elemento psicologico – colposo – effettivamente posseduto dal concorrente che non volle il reato diverso. Vi sarebbe, in altri termini, una sproporzione tra il fatto strutturalmente colposo e la sanzione – prevista per il reato doloso – concretamente applicata. Pertanto, oltre che con il principio delle personalità della responsabilità penale, si potrebbe configurare una violazione dell'art. 116 c.p. anche con i principi di ragionevolezza e di proporzione della sanzione penale, desumibili dall'art. 27 Cost., nonché dall'art. 3 Cost. In ultimo, per completezza di trattazione, dopo aver analizzato tutti i profili di compatibilità costituzionale dell'art. 116 c.p., il lavoro di ricerca si sofferma ad analizzare i più recenti progetti di riforma del codice penale per comprendere in che modo le diverse Commissioni di riforma hanno cercato di recuperare quella tanto auspicata dimensione costituzionale del concorso anomalo, richiesta dalla Consulta già con la sentenza 42 del 1965, ma allo stato non ancora realizzata.

Obra perteneciente al Fondo Antiguo de la Biblioteca de la USAL

ex singulari codice privatae bibliothecae Pii VI. P.O.M. edidit variisque dissertationibus illustravit Iohannes Bernardus de Rossi ...

Background The aims of this study were: to investigate the capacity of the rare disease healthcare network in Campania to diagnose patients with rare diseases during the outbreak of Covid-19; and to shed light on problematic diagnoses during this period. Methods To describe the impact of the Covid-19 pandemic on the diagnosis of patients with rare diseases, a retrospective analysis of the Campania Region Rare Disease Registry was performed. A tailored questionnaire was sent to rare disease experts to investigate major issues during the emergency period. Results Prevalence of new diagnoses of rare disease in March and April 2020 was significantly lower than in 2019 (117 versus 317, P Conclusions This study describes the effects of the Covid-19 outbreak on the diagnosis of rare disease in a single Italian region and investigates potential issues of diagnosis and management during this period.

Background The rapid growth in the complexity of services and stringent quality requirements present a challenge to all healthcare facilities, especially from an economic perspective. The goal is to implement different strategies that allows to enhance and obtain health processes closer to standards. The Length Of Stay (LOS) is a very useful parameter for the management of services within the hospital and is an index evaluated for the management of costs. In fact, a patient's LOS can be affected by a number of factors, including their particular condition, medical history, or medical needs. To reduce and better manage the LOS it is necessary to be able to predict this value. Methods In this study, a predictive model was built for the total LOS of patients undergoing laparoscopic appendectomy, one of the most common emergency procedures. Demographic and clinical data of the 357 patients admitted at “San Giovanni di Dio e Ruggi d’Aragona” University Hospital of Salerno (Italy) had used as independent variable of the multiple linear regression model. Results The obtained model had an R2 value of 0.570 and, among the independent variables, the significant variables that most influence the total LOS were Age, Pre-operative LOS, Presence of Complication and Complicated diagnosis. Conclusion This work designed an effective and automated strategy for improving the prediction of LOS, that can be useful for enhancing the preoperative pathways. In this way it is possible to characterize the demand and to be able to estimate a priori the occupation of the beds and other related hospital resources.

Background and objectives Urinary albumin excretion and/or albumin to creatinine ratio are associated with CKD and higher risk of cardiovascular events. Several studies investigated the effect of reduced dietary sodium intake on urinary albumin excretion and/or albumin to creatinine ratio in adult patient populations, but the majority was inconclusive because of insufficient statistical power. A meta-analysis of the randomized, controlled trials available could overcome this problem and lead to more definitive conclusions. Design, setting, participants, & measurements A systematic search of the online databases available (from 1996 to October of 2014) was conducted of randomized, controlled trials that expressed urinary albumin excretion or albumin to creatinine ratio as the difference between the effects of two different sodium intake regimens. For each study, the mean difference and 95% confidence intervals were pooled using a random effect model. Heterogeneity, publication bias, subgroup, and meta-regression analyses were performed. Results Eleven studies met the predefined inclusion criteria and provided 23 cohorts with 516 participants and 1–6 weeks of follow-up time. In the pooled analysis, an average reduction in sodium intake of 92 mmol/d was associated with a 32.1% (95% confidence interval, −44.3 to −18.8) reduction in urinary albumin excretion. The effect of sodium restriction was higher in the cohorts including patients on concomitant renin-angiotensin-aldosterone system–blocking therapy, in the studies with intervention lasting at least 2 weeks, and among participants with evidence of kidney damage. A greater reduction of urinary albumin excretion was associated with a higher decrease in BP during the intervention. The analysis of changes in albumin to creatinine ratio provided similar results. Conclusions This meta-analysis indicates that sodium intake reduction markedly reduces albumin excretion, more so during concomitant renin-angiotensin-aldosterone system–blocking therapy and among patients with kidney damage.

Epithelial‑to‑mesenchymal transition (EMT) confers stem cell‑like phenotype and more motile properties to carcinoma cells. During EMT, the expression of E‑cadherin decreases, resulting in loss of cell‑cell adhesion and increased migration. Expression of Twist1 and other pleiotropic transcription factors, such as Snail, is known to activate EMT. We established primary colon cancer cell cultures from samples of operated patients and validated cultures by cytogenetic and molecular biology approaches. Western blot assay, quantitative real‑time PCR and immunofluorescence were performed to investigate the expression of E‑cadherin, vimentin, β‑catenin, cytokeratin‑20 and ‑18, Twist1, Snail, CD44, cyclooxygenase‑2 (COX2), Sox2, Oct4 and Nanog. Moreover, cell differentiation was induced by incubation with LiCl‑containing medium for 10 days. We observed that these primary colorectal cancer (CRC) cells lost expression of the E‑cadherin epithelial marker, which was instead expressed in cancer and normal colon mucosa of the same patient, while overexpressed vimentin (mesenchymal marker), Twist1, Snail (EMT markers) and COX2. Cytokeratin‑18 was expressed both in tissues and cell cultures. Expression of stem cell markers, such as CD44, Oct4 and Nanog, were also observed. Following differentiation with the glycogen synthase kinase 3β (GSK3β) inhibitor LiCl, the cells began to express E‑cadherin and, at once, Twist1 and Snail expression was strongly downregulated, suggesting a MET‑reverting process. In conclusion, we established primary colon mesenchymal cancer cell cultures expressing mesenchymal and epithelial biomarkers together with high level of EMT transcription factors. We propose that they could represent a good model for studying EMT and its reverting mechanism, the mesenchymal‑to‑epithelial transition (MET). Our observation indicates that LiCl, a GSK3β inhibitor, induces MET in vitro, suggesting that LiCl and GSK3β could represent, respectively, interesting drug, and target for CRC therapy.

Background: Few epidemiological investigations evaluated the role of smoking cessation on blood pressure (BP), and the results are not univocal. Therefore, the aim of this study was to assess the effect of smoking cessation on the risk to develop hypertension (HPT) and on BP values. Methods: This longitudinal study, with a follow-up period of 8 years, included the participants of the Olivetti Heart Study. Participants were 430 untreated normotensive non-diabetic men with normal renal function, examined twice in 1994–95 and in 2002–04. The sample included current smokers (S, n = 212), former smokers (ES, n = 145) and never smokers (NS, n = 73) at baseline. Results: Basal body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were significantly higher in ES than in S (ES vs. S; BMI: 27.0 ± 2.5 vs. 26.1 ± 2.9 kg/m2; P < 0.01; SBP/DBP: 121.2 ± 9.3/80.0 ± 5.8 vs. 19.1 ± 9.9/77.4 ± 6.7 mm Hg; P < 0.05; M ± SD). After 8 years of follow-up, BP changes (Δ) were significantly lower in ES than in S (ΔSBP/DBP: 12.6 ± 13.4/7.9 ± 8.1 vs. 16.0 ± 14.9/10.3 ± 10.1 mm Hg; P < 0.05; M ± SD), also after adjustment for potential confounders. Moreover, at the last examination, the overall HPT prevalence was 33%, with lower values in ES than in S (25 vs. 38%, P = 0.01). After accounting for age, BP and BMI at baseline, and changes in smoking habit over the 8-year period, ES still had significant lower risk of HPT than S (odds ratio 0.30, 95% confidence interval 0.15–0.58; P < 0.01). Conclusions: In this sample of healthy men, smoking cessation was associated with lower BP increment and minor HPT risk, independently of potential confounders.

BACKGROUND AND AIM: High leptin (LPT) is associated with high blood pressure (BP), insulin resistance and systemic inflammation but also excess body weight and adiposity. To disentangle these multiple relations, we analyzed BP, HOMA and circulating C-reactive protein concentration (hs-CRP) in white male adults with different LPT levels but similar age, body mass index (BMI) and body fat distribution. The novel aspect is the different statistical approach used to investigate the relation between LPT and the other alterations present in obesity. METHODS AND RESULTS: 972 Olivetti Heart Study participants were stratified according to the median LPT distribution (2.97 ng/ml) into low LPT (l-LPT) and high LPT (h-LPT). The two groups were then carefully matched for age and BMI. We identified two groups of 207 h-LPT and 207 l-LPT individuals with overlapping age, BMI and waist/hip ratio. The two groups had different BP (132.9 ± 16.2/85.7 ± 9.0 vs 128.7 ± 18.2/82.8 ± 9.8 mmHg, p = 0.014 for SBP and p = 0.002 for DBP) and prevalence of hypertension (57% vs 43%, p = 0.027). Upon separate evaluation of untreated individuals with BMI < 25 or BMI ≥ 25, within the latter subgroup h-LPT compared with l-LPT participants (n = 133 each group) had higher BP (p = 0.0001), HOMA index (p = 0.013), hs-CRP (p = 0.002) and heart rate (p = 0.008) despite similar age and BMI. By contrast, within the normal weight subgroup, h-LPT individuals did not differ from l-LPT (n = 37 each) for any of these variables. CONCLUSIONS: High LPT is associated with higher BP, HR, hs-CRP and HOMA index independently of BMI and fat distribution but only among overweight individuals

Prevalence, incidence and predictors of resistant hypertension (RH), (defined as blood pressure persistently above goal in spite of the concurrent use of three antihypertensive agents of different classes) in the general population remain largely unknown. A complete database including anthropometric and biochemical data was collected in 1994-1995 (baseline examination) in 1,019 participants (mean age 51.8, range: 25-79 years) and again in 2002-2004 in 794 male participants of the Olivetti Heart Study (OHS) in southern Italy. The incidence of RH over the average follow-up time of 7.9 years was 4.8% (38/794) in the whole study population and 10.1% (31/307) among hypertensive participants. Basal blood pressure (systolic, diastolic or pulse pressure), cholesterol and urinary albumin/creatinine ratio (ACR) significantly predicted the risk of developing RH using a logistic regression model that also included age as covariates. If in the same model we added basal pharmacological treatment, the fractional excretion of sodium (FENa) also became a statistically significant predictor, and this last model explained nearly 25% of the risk of developing RH. In this unselected sample of an adult male population, ACR (an early marker of organ damage), an elevated FENa (a proxy for dietary sodium intake), cholesterol and a higher basal blood pressure level were independent predictors of RH.

OBJECTIVES: A model for predicting respiratory syncytial virus hospitalization in infants born 33-35 weeks' gestational age (wGA) has been developed from the Spanish FLIP study risk factors. The model correctly classified 71% of cases and the area under the receiver operating characteristic (ROC) curve was 0.791. To assess its applicability in Italy, the model was validated against data from the Osservatorio VRS study. METHODS: Discriminant function analysis was used to validate the model by (a) using the predictive variables identified in FLIP to generate a function from the Italian data and (b) applying the coefficients from the FLIP calculations to the Italian data. RESULTS: The function calculated from the Italian data provided 77% accurate classification (ROC: 0.773). Applying the FLIP coefficients to the Italian data resulted in correctly classifying 68% of cases and a ROC of 0.760. The number needed to treat to prevent hospitalization of 80% of at risk infants was 13.4, based on a hospitalization rate of 5% and 80% treatment efficacy. CONCLUSIONS: The Italian data confirm the predictive ability of the model, which could be used to target palivizumab prophylaxis in Italian infants born 33-35 wGA.

The key role of respiratory syncytial virus (RSV) in causing infant morbidity and hospitalizations is worldwide well recognized. The late preterm infants (34-36 weeks of gestational age (WGA)) showed a higher risk of hospitalization for RSV-induced infection as compared with full-term infants and similar to that seen in very preterm infants. In addition to the prematurity, a number of risk factors have been identified in 33-35 WGA infants that are associated with RSV-hospitalization as demonstrated by the Canadian and the Spanish studies. However, prematurity per se is not the only factor, since RSV-hospitalization in the first year of life also occurs in numerous full-term and previously healthy infants. Indeed, a recent case-control study on mostly full-term children showed that chronological age at the beginning of RSV season, low birth weight, and birth order (>or=1 sibling) were associated with a higher likelihood to acquire RSV-induced LRTI, severe enough to lead to hospital admission. In order to maximize the cost effectiveness of immunoprophylaxis with palivizumab, the American Academy of Pediatrics have recently updated recommendations resulting in a restriction of its use to infants at highest risk of hospitalization during times when RSV is most likely to be circulating (i.e. in the first 3 months of life for late preterm infants). According to a variety of epidemiologic data in this gestational age group, the risk of exposure should include day-care attendance and having a sibling

Pulmonary arteriovenous Malformations (PAVMs) are a rare vascular alteration characterized by abnormal communications between the pulmonary arteries and veins resulting in an extracardiac right-to-left (R-L) shunt. The majority of PAVMs are associated with an autosomal dominant vascular disorder also known as Osler-Weber- Rendu Syndrome. PAVMs appearance can be both single and multiple. Clinical manifestations include hypoxemia, dyspnea cyanosis, hemoptysis and cerebrovascular ischemic events or abscesses. We report a case of an 18 year old female with severe respiratory failure caused by a relapse of multiple unilateral pulmonary arterovenous fistula. Symptoms at admission include dyspnea, cyanosis and clubbing. The patient underwent pulmonary angio-TC scan, brain CT and echocardiography. The thoracic angio-CT scan showed the presence of PAVMs of RUL and RLL; a marked increase of right bronchial artery caliber and its branches with an aneurismatic dilatation was also observed. The patient underwent percutaneous transcatheter embolization using Amplatzer Vascular Plug IV; a relevant clinical and functional improvement was subsequently recorded. Embolization is effective in the treatment of relapsing PAVMS.

Respiratory syncytial virus (RSV) is the leading cause of respiratory tract infection in infants and young children throughout the world. Although preterm birth has been considered for years the major risk factor for severe disease and hospitalization, recent findings indicate that prematurity is not a necessary condition, but one of the independent risk factors for severe RSV infection, together with chronic lung diseases, congenital heart disease and immunodeficiency. Furthermore, over 50% of infants hospitalized for RSV infections during the first year of life are healthy, full-term newborns, suggesting that other environmental and individual factors may be involved. Unfortunately, there is still no specific therapy against RSV infection and therefore prophylactic measures seem to be the only intervention to avoid disease complications. No safe and effective RSV vaccine is available for the prevention of serious RSV infection. Therefore, in addition to hygienic measures, the only approach is passive immunoprophylaxis with humanized monoclonal anti-RSV antibodies, such as palivizumab that have been developed for clinical use. Because of the high cost of these antibodies, a better definition of the individual risk profile for severe RSV infection and timing of administration is needed for optimal effectiveness and careful use of limited health care resources. In this article, we have reviewed the clinical and pharmacological aspects of immunoprophylaxis with monoclonal antibodies for preventing RSV infection in high-risk infants.

In the last decades the preterm birth rate rose more than 20%, largely because of an increase among deliveries of 'late preterm' infants, i.e. those born at 34 to 36 weeks gestational age. Late preterm infants are more susceptible to infection by pathogens, such as respiratory syncytial virus (RSV), possibly because of the immaturity of both the respiratory system and the immune system. As a consequence, similar risks of serious RSV illness have been observed in late preterm and preterm (born ≤ 32 wGA) infants, higher when compared with full-term infants. Prevention of RSV infection includes palivizumab, which is proven to be effective in reducing the overall hospitalization rate for RSV-induced bronchiolitis in preterm neonates. In order to maximize the cost-effectiveness of this preventive approach, the American Academy of Pediatrics (AAP) has suggested the administration of palivizumab to infants born between 32 0/7 and 34 6/7 wGA with at least one risk factor and born 3 months before or during RSV season. Because a variety of environmental and demographic traits may affect the severity of RSV epidemics in different Nations, a European risk scoring tool has been developed, based on the 'local' most important risk factors. Therefore, recommendations and guidelines must be modulated in each country, determining their appropriateness in the individual setting.