Five-year retrospective italian multicenter study of visceral leishmaniasis treatment

The treatment of visceral leishmaniasis (VL) is poorly standardized in Italy in spite of the existing evidence. All consecutive patients with VL admitted at 15 Italian centers as inpatients or outpatients between January 2004 and December 2008 were retrospectively considered; outcome data at 1 year after treatment were obtained for all but 1 patient. Demographic characteristics, underlying diseases, diagnostic procedures, treatment regimens and outcomes, as well as side effects were recorded. A confirmed diagnosis of VL was reported for 166 patients: 120 (72.3%) immunocompetent, 21 (12.6%) patients with immune deficiencies other than HIV infection, and 25 (15.1%) coinfected with HIV. Liposomal amphotericin B (L-AmB) was the drug almost universally used for treatment, administered to 153 (92.2%) patients. Thirty-seven different regimens, including L-AmB were used. The mean doses were 29.4 \ub1 7.9 mg/kg in immunocompetent patients, 32.9 \ub1 8.6 mg/kg in patients with non-HIV-related immunodeficiencies, and 40.8 \ub1 6.7 mg/kg in HIV-infected patients (P < 0.001). The mean numbers of infusion days were 7.8 \ub1 3.1 in immunocompetent patients, 9.6 \ub1 3.9 in non-HIV-immunodeficient patients, and 12.0 \ub1 3.4 in HIV-infected patients (P < 0.001). Mild and reversible adverse events were observed in 12.2% of cases. Responsive patients were 154 (93.3%). Successes were 98.4% among immunocompetent patients, 90.5% among non-HIV-immunodeficient patients, and 72.0% among HIV-infected patients. Among predictors of primary response to treatment, HIV infection and age held independent associations in the final multivariate models, whereas the doses and duration of L-AmB treatment were not significantly associated. Longer treatments and higher doses of L-AmB were not able to significantly modify treatment outcomes either in the immunocompetent or in the immunocompromised population

Edge reductions in cyclically k-connected cubic graphs

AbstractThis paper examines edge reductions in cyclically k-connected cubic graphs, focusing on when they preserve the cyclic k-connectedness. For a cyclically k-connected cubic graph G, we denote by Nk(G) the set of edges whose reduction gives a cubic graph which is not cyclically k-connected. With the exception of three graphs, Nk(G) consists of the edges in independent k-edge cuts. For this reason we examine the properties and interactions between independent k-edge cuts in cyclically k-connected cubic graphs. These results lead to an understanding of the structure of G[Nk]. For every k, we prove that G[Nk] is a forest with at least k trees if G is a cyclically k-connected cubic graph with girth at least k + 1 and Nk ≠ ⊘. Let fk(ν) be the smallest integer such that |Nk(G)| ≤ fk(ν) for all cyclically k-connected cubic graphs G on ν vertices. For all cyclically 3-connected cubic graphs G such that 6 ≤ ν(G) and N3 ≠ ⊘, we prove that G[N3] is a forest with at least three trees. We determine f3 and state a characterization of the extremal graphs. We define a very restricted subset N4b of N4 and prove that if N4g = N4 − N4b ≠ ⊘, then G[N4g] is a forest with at least four trees. We determine f4 and state a characterization of the extremal graphs. There exist cyclically 5-connected cubic graphs such that E(G) = N5(G), for every ν such that 10 ≤ ν and 16 ≠ ν. We characterize these graphs. Let gk(ν) be the smallest integer such that |Nk(G)| ≤ gk(ν) for all cyclically k-connected cubic graphs G with ν vertices and girth at least k + 1. For k ∈ {3, 4, 5}, we determine gk and state a characterization of the extremal graphs

Studio del rapporto fra Metcalfa pruinosa (Say) e Neodryinus typhlocybae (Ashmead) mediante utilizzo di Geostatistica e GIS

Comparso in Europa alla fine degli anni Settanta, in provincia di Treviso, l’omottero flatide nordamericano Metcalfa pruinosa si è rapidamente diffuso nella quasi totalità del territorio italiano e in alcuni stati europei con esso confinanti, favorito da una notevole polifagia e dall’assenza di specifici ed efficaci antagonisti naturali. Giovani e adulti della specie si sviluppano a spese di innumerevoli piante erbacee, arbustive ed arboree, interessando in molti casi anche piante coltivate. I danni ad esse arrecati sono dovuti, oltre che all’intensa sottrazione di linfa, anche ai cospicui imbrattamenti con cera e all’abbondante produzione di melata che supporta lo sviluppo di fumaggini. Alcuni aspetti bioetologici e fisiologici che la caratterizzano, rendono M. pruinosa un insetto poco adatto ad essere contrastato con il mezzo chimico. Per questo, il ricorso al controllo biologico classico, da attuarsi attraverso l’introduzione di efficaci e specifici antagonisti rinvenuti nel Paese di origine del fitofago, è parsa la strategia più ragionevole per fronteggiare efficacemente il dilagare del fitomizo nel nostro e negli altri Paesi europei. L’introduzione dell’Imenottero Driinide Neodryinus typhlocybae (Ashmead) ha consentito un efficace contenimento del fitofago nel breve-medio termine. I numerosi progetti di lotta biologica alla Metcalfa con tale entomofago condotti in alcune regioni italiane nell’ultimo decennio hanno fornito, infatti, risultati estremamente positivi. I due insetti sono stati oggetto, negli ultimi anni, di numerosi studi e - di conseguenza – di altrettante pubblicazioni concernenti aspetti di biologia, fenologia, morfologia e fisiologia. In questa occasione, facendo ricorso al GIS ed alla Geostatistica, si è inteso studiare il rapporto che le due specie instaurano tra loro e con i fattori biotici (ed es. assetto vegetazionale) e abiotici (ad es. microclima) dell’ambiente che le ospita. Le più significative acquisizioni rese disponibili dal presente studio sono di seguito elencate. - Le popolazioni più cospicue di Metcalfa, corrispondenti alle classi di infestazione 3 e 4, sono state rilevate nelle aree più ombreggiate e umide, mentre su vegetazione esposta ad insolazione diretta per molte ore del giorno il fitofago è risultato pressoché assente. In ambiente urbano tale situazione si riscontra in corrispondenza di siepi di ampie dimensioni o anche di aree verdi di dimensioni ridotte purché ombreggiate per gran parte della giornata da palazzi o da alberi di alto fusto presenti nelle vicinanze. - Come era logico attendersi, la presenza di N. typhlocybae si è rilevata consistente soprattutto in quei punti nei quali, nel monitoraggio estivo, era stata rinvenuta una maggiore presenza di M. pruinosa. Tuttavia, appare degno di nota il fatto che l’entomofago sia stato riscontrato ad alte densità anche in alcune stazioni di monitoraggio nelle quali i rilievi primaverili di M. pruinosa avevano evidenziato un basso livello di infestazione. - La presenza di bozzoli del Driinide ad una distanza considerevole già a partire dai mesi successivi al primo rilascio nell’area di Ameglia ha dimostrato la predisposizione dell’insetto a diffondersi rapidamente sul territorio alla ricerca del proprio ospite. La massima distanza in corrispondenza della quale sono stati individuati reperti biologici (bozzoli) dell’entomofago è stata pari rispettivamente a 750 e 2500 mt a 5 e 18 mesi dal rilascio. Il rinvenimento di bozzoli, a cinque mesi dal rilascio, sulla sponda opposta del fiume Magra, che in quel punto ha una larghezza di circa 150 mt, denota una forte attitudine al volo e una spiccata capacità di ricerca dell’ospite da parte dell’Imenottero, se non altro allo stato femminile. Questo dato è confermato anche dalle osservazioni condotte sull’intero territorio comunale di Carrara, nel quale il neodrino, dopo essere stato introdotto per 4 anni consecutivi in 4 diverse località, è ormai diffusamente presente ad elevate densità. - Il GIS e la geostatistica hanno consentito la creazione di mappe previsionali di isovalore relative al fitofago anche in aree lontane dal punto campionato. L’analisi dei semivariogrammi ha rivelato un buon grado di correlazione spaziale del livello di infestazione di M. pruinosa ogni qual volta venisse utilizzata come parametro di riferimento la media delle classi di infestazione per ciascun punto. - A Marina di Carrara la sovrapposizione delle mappe relative alla presenza del fitofago nei due anni di studio ha evidenziato una netta diminuzione delle popolazioni di quest’ultimo da un anno all’altro in seguito all’azione dell’entomofago, denotando, tra l’altro, un’inattesa e sorprendente rapidità nella regolazione demografica dell’ospite. Quanto detto contrasta con precedenti studi condotti in altre regioni italiane, nei quali il Driinide era ritenuto incapace di colonizzare territori vasti nel breve periodo. - Nell’area di Ameglia, facendo riferimento al 2003, primo anno di rilascio del driinide, e considerando come parametri di riferimento la media dei bozzoli pieni (monovoltini) e la media di quelli vuoti (bivoltini), è stato possibile osservare una diversa distribuzione degli stessi sulle due piante considerate. Mentre i primi sono presenti quasi equamente nelle due specie vegetali, quelli vuoti sono risultati più numerosi su pittosporo, suggerendo una maggiore predisposizione di tale pianta ad ospitare individui bivoltini rispetto al rovo. - I rilievi condotti nell’intero territorio del comune di Carrara, la cui superficie è pari a 71 kmq, hanno confermato la validità del protocollo attuato tra il 2001 e il 2004. Un unico rilascio di 100 maschi e 100 femmine in ciascuna delle quattro località comunali ha portato, nel volgere di quattro anni, ad una diffusa presenza del parassitoide in pressoché tutte le aree comunali nelle quali sono state svolte le indagini. - Sebbene si riferiscano ad un periodo di tempo limitato, i dati in nostro possesso ci consentono di affermare che il sistema biologico neodrino-metcalfa-pittosporo si è rivelato assai adatto per lo studio geostatistico delle relazioni tritrofiche in oggetto. - Pur non trascurando il ruolo svolto da predatori indigeni via via adattatisi all’“ospite straniero”, i risultati ottenuti portano a considerare il neodrino come il principale artefice della appariscente diminuzione sul territorio delle popolazioni del flatide

Epidemiology and Microbiology of Skin and Soft Tissue Infections: Preliminary Results of a National Registry

Skin and soft tissue infections (SSTIs) represent a wide range of clinical conditions characterized by a considerable variety of clinical presentations and severity. Their aetiology can also vary, with numerous possible causative pathogens. While other authors previously published analyses on several types of SSTI and on restricted types of patients, we conducted a large nationwide surveillance programme on behalf of the Italian Society of Infectious and Tropical Diseases to assess the clinical and microbiological characteristics of the whole SSTI spectrum, from mild to severe life-threatening infections, in both inpatients and outpatients. Twenty-five Infectious Diseases (ID) Centres throughout Italy collected prospectively data concerning both the clinical and microbiological diagnosis of patients affected by SSTIs via an electronic case report form. All the cases included in our database, independently from their severity, have been managed by ID specialists joining the study while SSTIs from other wards/clinics have been excluded from this analysis. Here, we report the preliminary results of our study, referring to a 12-month period (October 2016–September 2017). During this period, the study population included 254 adult patients and a total of 291 SSTI diagnoses were posed, with 36 patients presenting more than one SSTIs. The type of infection diagnosed, the aetiological micro-organisms involved and some notes on their antimicrobial susceptibilities were collected and are reported herein. The enrichment of our registry is ongoing, but these preliminary results suggest that further analysis could soon provide useful information to better understand the national epidemiologic data and the current clinical management of SSTIs in Italy

Safety evaluation of current therapies for high-risk severely ill patients with carbapenem-resistant infections

Introduction Infections due to carbapenem-resistant Gram-negative bacteria (CR-GNB) are increasingly frequent events, which are associated with a high mortality rate. Traditionally, combination regimens including high doses of "old antibiotics" such as polymyxins, tigecycline, and aminoglycosides have been used to treat these infections, but they were often associated with low efficacy and high excess of side effects and toxicity, especially nephrotoxicity. Along with the development of new compounds, the last decade has seen substantial improvements in the management of CR infections. Areas covered In this review, we aimed to discuss the safety characteristics and tolerability of different new options for treatment of CR infections. Expert opinion The availability of new drugs showing a potent in vitro activity against CR-GNB represents a unique opportunity to face the threat of resistance, while potentially reducing toxicity. A thorough understanding of the safety profile from clinical trials may guide the use of these new drugs in critically ill patients at high risk for the development of adverse events. Future data coming from real-life studies for drugs targeting CR infections are crucial to confirm the safety profile observed in pivotal trials

Original Article

The pancreas taken from the frog (Rana nigromaculata) was fixed in 1% OsO_4 and sliced into ultrathin sections for electron microscopic studies. The following observations were made: 1. A great \u27number of minute granules found in the cytoplasm of a pancreatic cell were called the microsomes, which were divided into two types, the C-microsome and S-microsome. 2. Electron microsopic studies of the ergastoplasm showed that it is composed of the microsome granules and A-substance. The microsomes were seen embedded in the A-substance which was either filamentous or membranous. The membranous structure, which was called the Am-membrane, was seen to form a sac, with a cavity of varying sizes, or to form a lamella. 3. The Am-membrane has close similarity to α-cytomembrane of Sjostrand, except that the latter is rough-surfaced. It was deduced that the Am-membrane, which is smooth-surfaced, might turn into the rough-surfaced α-cytomembrane. 4. There was the Golgi apparatus in the supranuclear region of a pancreatic cell. It consisted of the Golgi membrane, Golgi vacuole and. Golgi vesicle. 5. The mitochondria of a pancreatic cell appeared like long filaments, and some of them were seen to ramify. 6. The membrane of mitochondria, i. e. the limiting membrane, consisted of the Ammembrane. The mitochondria contained a lot of A-substances, as well as the C-microsomes and S-microsomes. When the mitochondria came into being, there appeared inside them chains of granules, which appeared like strips of beads, as the outgrowths of the A-substance and the microsome granules attached to the Am-membrane. They are the so-called cristae mitochondriales. 7. The secretory granules originate in the microsomes. They came into being when the microsomes gradually thickened and grew in size as various substances became adhered to them. Some of the secretory granules were covered with a membrane and appeared like what they have called the intracisternal granule of Palade.It seemed that this was a phenomenon attendant upon the dissolution and liqutefaction of the secretory granule. 8. Comparative studies were made of the ergastoplasm of the pancreatic cells from the frogs in hibernation, the frogs artificially hungered, the frogs which were given food after a certain period of fasting, the frogs to which pilocarpine was given subcutaneously, and the very young, immature frogs. The studies revealed that the ergastoplasm of the pancreatic cells greatly varied in form with the difference in nutritive condition and with different developmental stages of the cell. The change in form and structure occured as a result of transformation of the microsomes and A-substance. The ergastoplasm, even after it has come into being, might easily be inactivated if nutrition is defective. The ergastoplasm is concerned in the secretory mechanism, which is different from the secretory phenomenon of the secretory granules. It would seem that structurally the mitochondria have no direct relation to this mechanism

Nine ideas to improve the clinical management of HIV infected patients during the COVID-19 pandemic

Globally, in 2019, HIV infection was still responsible for 1.7 million new infections 2.2 and for 690,000 deaths in the same year. Tailored and new antiretroviral therapy (ART) regimens, individualised follow-up and new technologies to support data-sharing between health—care professional caring for people living with HIV (PLHIV) and to deliver ART to patients are desperately needed to reach the 90-90-90-90 ambitious goals. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, responsible for the Coronavirus-19 (COVID-19) pandemic that spread globally in 2020, posed a huge challenge for PLHIV and HIV physicians worldwide in terms of continuum of care.In this paper we encourage “up-to-date patient-centred HIV medicine” and we give nine ideas to improve HIV management in clinical practice during the COVID-19 pandemic

Cost per care of the first year of direct antiviral agents in the liguria region: A multicenter analysis

Aims: Despite the remarkable efficacy shown in clinical practice, concerns have been raised about the costs associated with direct antiviral agent (DAA) therapy. This article presents the real-life costs for DAA treatment sustained by the Italian National Health Service in the Liguria Region (Northern Italy). Methods: A retrospective analysis of the cost per care sustained for DAA treatment, relating to the period from January 1 to December 31, 2015 in five centers in Liguria was performed. All patients undergoing DAA-based treatments for hepatitis C virus (HCV) infection were enrolled. On-treatment costs included: HCV treatment, laboratory test, outpatient services, attended visits, drugs used for the management of adverse events (erythropoietin, albumin or red blood cell packs) and inpatient service admissions. Results: In total, 327 patients were enrolled. No difference in terms of sustained virologic response (SVR) rate among different treatments was reported. The majority (85.0%) of patients did not report any side effects and only 15 (4.6%) required hospital admission. Forty-two patients (12.8%) required high-cost drugs for the management of adverse events. The overall cost sustained was \u20ac14,744,433. DAA\ub1ribavirin (RBV) accounted for the wide majority of this cost (98.9%; \u20ac14,585,123). Genotype (GT) 1, the most commonly treated GT, was associated with an average cost of \u20ac43,445 per patient. Detailed analysis of the costs for GT 1 showed the treatment based on ritonavir boosted paritaprevir/ombitasvir + dasabuvir\ub1RBV with an average cost of \u20ac24,978 (RBV+) and \u20ac25,448 (RBV 12) per patient was the most cost-effective. The average cost per SVR was \u20ac48,184. Once again, the ritonavir boosted paritaprevir/ ombitasvir + dasabuvir regimen was associated with the lowest cost/SVR (\u20ac25,448/SVR [GT 1b] and similar results for other GTs). Conclusion: Antiviral regimen is the major contributor to costs in the treatment of HCV infection. Appropriate regimen selection could result in a major cost saving, which can be reinvested to allow more patients to be treated

Ten Years of Medical Informatics and Standards Support for Clinical Research in an Infectious Diseases Network

Background It is 30 years since evidence-based medicine became a great support for individual clinical expertise in daily practice and scientific research. Electronic systems can be used to achieve the goal of collecting data from heterogeneous datasets and to support multicenter clinical trials. The Ligurian Infectious Diseases Network (LIDN) is a web-based platform for data collection and reuse originating from a regional effort and involving many professionals from different fields. Objectives The objective of this work is to present an integrated system of ad hoc interfaces and tools that we use to perform pseudonymous clinical data collection, both manually and automatically, to support clinical trials. Methods The project comprehends different scenarios of data collection systems, according to the degree of information technology of the involved centers. To be compliant with national regulations, the last developed connection is based on the standard Clinical Document Architecture Release 2 by Health Level 7 guidelines, interoperability is supported by the involvement of a terminology service. Results Since 2011, the LIDN platform has involved more than 8,000 patients from eight different hospitals, treated or under treatment for at least one infectious disease among human immunodeficiency virus (HIV), hepatitis C virus, severe acute respiratory syndrome coronavirus 2, and tuberculosis. Since 2013, systems for the automatic transfer of laboratory data have been updating patients' information for three centers, daily. Direct communication was set up between the LIDN architecture and three of the main national cohorts of HIV-infected patients. Conclusion The LIDN was originally developed to support clinicians involved in the project in the management of data from HIV-infected patients through a web-based tool that could be easily used in primary-care units. Then, the developed system grew modularly to respond to the specific needs that arose over a time span of more than 10 years