Imaging features of perineural and perivascular spread in rapidly progressive rhino-orbital-cerebral mucormycosis: A case report and brief review of the literature

Background: Rhinocerebral mucormycosis (ROCM) is an opportunistic fungal infection originating from the paranasal sinuses with extension to the brain. A delayed diagnosis can rapidly result in a poor prognosis. ROCM commonly affects patients with diabetes or immunocompromised states with a variable progression. Case description: We report the case of a 59-year old patient with an untreated diabetes who developed a ROCM with rapidly progressive neurological symptoms. From the onset of sinus pain, nasal congestion, he rapidly developed facial swelling and masticatory dysfunction. The patient underwent sinus surgery which allowed Rhizopus oryzae to be isolated. Accordingly, a systemic therapy by intensive intravenous amphotericin B was started. Nevertheless, the infection rapidly resulted in bilateral cavernous sinuses thrombosis and occlusion of the left internal carotid artery providing the subsequent patient death. Conclusion: Mucormycosis is a life-threatening fungal infection in diabetic and/or immunosuppressed patients. Our case demonstrates the three main mechanisms for infection spreading that are direct, perineural, and perivascular diffusion. Clear identification of the main risk factors, proper assessment of clinical features, and radiological findings may improve the chance for an early diagnosis and patient survival

Methotrexate Increases Skeletal Muscle GLUT4 Expression and Improves Metabolic Control in Experimental Diabetes

Long-term administration of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) mimics the effects of endurance exercise by activating AMP kinase and by increasing skeletal muscle expression of GLUT4 glucose transporter. AICAR is an intermediate in the purine de novo synthesis, and its tissue concentrations can be increased, in vivo, by low doses of methotrexate (MTX) through the inhibition of the enzyme AICAR transformylase. We report here the first evidence that, in experimental type 2 diabetes, chronic treatment with low doses of MTX increases skeletal muscle GLUT4 expression and improves metabolic control. MTX (0.5 mg/kg body weight) or vehicle was administered intraperitoneally, once a week for 4 weeks, to genetically diabetic female C57BL/KsJ-m+/+Leptdb mice (db+/db+) and their normoglycemic littermates (db+/+m). In the db+/db+ mice, MTX treatment was associated with a ∼2-fold increase in skeletal muscle GLUT4 protein concentration and a >4-fold increase in GLUT4 mRNA expression (P<0.01, all), as compared to vehicle-treated mice; no significant differences were noted in controls. MTX treatment was also associated with a significant reduction of glucose and insulin serum concentrations in diabetic mice (P<0.001), and glucose levels only (P<0.05) in controls. These data indicate a different route to increase skeletal muscle GLUT4 expression, through the potential inhibition of the enzyme AICAR transformylase

Risk of progression in chronic phase-chronic myeloid leukemia patients eligible for tyrosine kinase inhibitor discontinuation: Final analysis of the TFR-PRO study

Disease progression to accelerated/blast phase (AP/BP) in patients with chronic phase chronic myeloid leukemia (CP-CML) after treatment discontinuation (TD) has never been systematically reported in clinical trials. However, recent reports of several such cases has raised concern. To estimate the risk of AP/BP among TD-eligible patients, we conducted TFR-PRO, a cohort retro-prospective study: 870 CP-CML patients eligible for TD formed a discontinuation cohort (505 patients) and a reference one (365 patients). The primary objective was the time adjusted rate (TAR) of progression in relation to TD. Secondary endpoints included the TAR of molecular relapse, that is, loss of major molecular response (MMR). With a median follow up of 5.5 years and 5188.2 person-years available, no events occurred in the TD cohort. One event of progression was registered 55 months after the end of TD, when the patient was contributing to the reference cohort. The TAR of progression was 0.019/100 person-years (95% CI [0.003-0.138]) in the overall group; 0.0 (95% CI [0-0.163]) in the discontinuation cohort; and 0.030 (95% CI [0.004-0.215]) in the reference cohort. These differences are not statistically significant. Molecular relapses occurred in 172/505 (34.1%) patients after TD, and in 64/365 (17.5%) patients in the reference cohort, p &lt; .0001. Similar rates were observed in TD patients in first, second or third line of treatment. CML progression in patients eligible for TD is rare and not related to TD. Fears about the risk of disease progression among patients attempting TD should be dissipated

Low low-density lipoprotein (LDL), cholesterol and triglycerides plasma levels are associated with reduced risk of arterial occlusive events in chronic myeloid leukemia patients treated with ponatinib in the real-life. A Campus CML study

not available (letter

Cardiovascular toxicity in patients with chronic myeloid leukemia treated with second-generation tyrosine kinase inhibitors in the real-life practice: Identification of risk factors and the role of prophylaxis

No abstract availabl

Determinants of frontline tyrosine kinase inhibitor choice for patients with chronic-phase chronic myeloid leukemia: A study from the Registro Italiano LMC and Campus CML

Background: Imatinib, dasatinib, and nilotinib are tyrosine kinase inhibitors (TKIs) approved in Italy for frontline treatment of chronic-phase chronic myeloid leukemia (CP-CML). The choice of TKI is based on a combined evaluation of the patient's and the disease characteristics. The aim of this study was to analyze the use of frontline TKI therapy in an unselected cohort of Italian patients with CP-CML to correlate the choice with the patient's features. Methods: A total of 1967 patients with CP-CML diagnosed between 2012 and 2019 at 36 centers throughout Italy were retrospectively evaluated; 1089 patients (55.4%) received imatinib and 878 patients (44.6%) received a second-generation (2G) TKI. Results: Second-generation TKIs were chosen for most patients aged &lt;45 years (69.2%), whereas imatinib was used in 76.7% of patients aged &gt;65 years (p&nbsp;&lt;&nbsp;.001). There was a predominant use of imatinib in intermediate/high European long-term survival risk patients (60.0%/66.0% vs. 49.7% in low-risk patients) and a limited use of 2G-TKIs in patients with comorbidities such as hypertension, diabetes, chronic obstructive pulmonary disease, previous neoplasms, ischemic heart disease, or stroke and in those with &gt;3 concomitant drugs. We observed a greater use of imatinib (61.1%) in patients diagnosed in 2018-2019 compared to 2012-2017 (53.2%; p&nbsp;=&nbsp;.002). In multivariable analysis, factors correlated with imatinib use were age &gt; 65 years, spleen size, the presence of comorbidities, and ≥3 concomitant medications. Conclusions: This observational study of almost 2000 cases of CML shows that imatinib is the frontline drug of choice in 55% of Italian patients with CP-CML, with 2G-TKIs prevalently used in younger patients and in those with no concomitant clinical conditions. Introduction of the generic formulation in 2018 seems to have fostered imatinib use

Managing chronic myeloid leukemia for treatment-free remission: a proposal from the GIMEMA CML WP

Several papers authored by international experts have proposed recommendations on the management of BCR-ABL1+ chronic myeloid leukemia (CML). Following these recommendations, survival of CML patients has become very close to normal. The next, ambitious, step is to bring as many patients as possible into a condition of treatment-free remission (TFR). The Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA; Italian Group for Hematologic Diseases of the Adult) CML Working Party (WP) has developed a project aimed at selecting the treatment policies that may increase the probability of TFR, taking into account 4 variables: the need for TFR, the tyrosine kinase inhibitors (TKIs), the characteristics of leukemia, and the patient. A Delphi-like method was used to reach a consensus among the representatives of 50 centers of the CML WP. A consensus was reached on the assessment of disease risk (EUTOS Long Term Survival [ELTS] score), on the definition of the most appropriate age boundaries for the choice of first-line treatment, on the choice of the TKI for first-line treatment, and on the definition of the responses that do not require a change of the TKI (BCR-ABL1 6410% at 3 months, 641% at 6 months, 640.1% at 12 months, 640.01% at 24 months), and of the responses that require a change of the TKI, when the goal is TFR (BCR-ABL1 &gt;10% at 3 and 6 months, &gt;1% at 12 months, and &gt;0.1% at 24 months). These suggestions may help optimize the treatment strategy for TFR

Osservazioni

di Calogero Piro. Convertire la realtà che ci circonda in immagini, è stata fin dai primordi dell’essere umano un’atavica necessità. Ancora oggi nella nostra cultura visiva è tutto basato sull’utilizzo dell’immagine per conoscere la realtà che ci circonda. Con la scoperta della fotografia, la riflessione intorno alla natura si fa sempre più interessante. Il ruolo della macchina fotografica in questo progetto per raccontare l’ambiente, la struttura, gli oggetti, i segni, i colori e le atmosfere che caratterizzano il centro del CNR di capo Granitola ha trovato prepotentemente in questi giovani allievi della cattedra di fotografia dell’Accademia di Belle Arti di Palermo, diretta dal Professore Sandro Scalia, momenti di grande professionalità, realizzando un grande reportage con tutti gli aspetti essenziali della struttura e delle articolazioni primarie del linguaggio fotografico. Questa esperienza extradidattica difficile ed impegnativa non soltanto per la necessità del confronto col “nuovo” in termini organizzativi, ma anche per la necessità di descrivere attraverso la fotografia il tema della Biodiversità, è stato affrontato brillantemente. Mettendo in primo piano, siti naturali, siti storici come: Mozia e Selinunte, i laboratori del centro di ricerche, la Flora e la Fauna, sono riusciti a raggiungere con acuta osservazione ottimi risultati visibili in questo catalogo, e con la tangibile riprova di cosa possa e debba essere una educazione estetica assolutamente “libera” da condizionamenti, viatico ineludibile perché l’espressione artistica, sotto qualunque forma, sia artefice dei grandi processi di vera maturazione culturale, si avverte in questi giovani artisti la purezza e la consapevolezza dei propri messaggi ancora privi, e speriamo sempre, di qualunque tipo di inquinamento tendenzioso

Inspecting the transformation of roman settlements in the Upper Potenza Valley (Marche region) across Late Antiquity and into the Early Medieval era

International audienc