Recent Advances in The Definition of the Molecular Alterations Occurring in Multiple Myeloma.

Multiple myeloma (MM) is a disorder of the monoclonal plasma cells and is the second most common hematologic malignancy. MM initiation and progression are dependent upon complex genomic abnormalities. The current pathogenic model of MM includes two types of primary events, represented by chromosome translocations or chromosome number alterations resulting in hyperdiploidy. These primary molecular events are observed both in MM and in monoclonal gammopathy, its premalignant precursor. Subsequent genetic events allow the progression of monoclonal gammopathy to MM and, together with primary events, contribute to the genetic complexity and heterogeneity of MM. Newer therapies have considerably improved patient outcomes; however, MM remains an incurable disease and most patients experience multiple relapses. The dramatic progresses achieved in the analysis of the heterogeneous molecular features of different MM patients allowed a comprehensive molecular classification of MM and the definition of an individualized prognostic model to predict an individual MM patient's response to different therapeutic options. Despite these progresses, prognostic models fail to identify a significant proportion of patients destined to early relapse. Treatment strategies are increasingly. Based on disease biology, trials are enriched for high-risk MMs, whose careful definition and categorization requires DNA sequencing studies.

Comparative Efficacy of Flow Diverter Devices in the Treatment of Carotid Sidewall Intracranial Aneurysms: a Retrospective, Multicenter Study.

BACKGROUND: The comparative efficacy and safety of first-generation flow diverters (FDs), Pipeline Embolization Device (PED) (Medtronic, Irvine, California), Silk (Balt Extrusion, Montmorency, France), Flow Re-direction Endoluminal Device (FRED) (Microvention, Tustin, California), and Surpass Streamline (Stryker Neurovascular, Fremont, California), is not directly established and largely inferred. PURPOSE: This study aimed to compare the efficacy of different FDs in treating sidewall ICA intracranial aneurysms. METHODS: We conducted a retrospective review of prospectively maintained databases from eighteen academic institutions from 2009-2016, comprising 444 patients treated with one of four devices for sidewall ICA aneurysms. Data on demographics, aneurysm characteristics, treatment outcomes, and complications were analyzed. Angiographic and clinical outcomes were assessed using various imaging modalities and modified Rankin Scale (mRS). Propensity score weighting was employed to balance confounding variables. The data analysis used Kaplan-Meier curves, logistic regression, and Cox proportional-hazards regression. RESULTS: While there were no significant differences in retreatment rates, functional outcomes (mRS 0-1), and thromboembolic complications between the four devices, the probability of achieving adequate occlusion at the last follow-up was highest in Surpass device (HR: 4.59; CI: 2.75-7.66, p < 0.001), followed by FRED (HR: 2.23; CI: 1.44-3.46, p < 0.001), PED (HR: 1.72; CI: 1.10-2.70, p = 0.018), and Silk (HR: 1.0 ref. standard). The only hemorrhagic complications were with Surpass (1%). CONCLUSION: All the first-generation devices achieved good clinical outcomes and retreatment rates in treating ICA sidewall aneurysms. Prospective studies are needed to explore the nuanced differences between these devices in the long term.

Is It Possible to Predict Tumor Progression Through Genomic Characterization of Monoclonal Gammopathy and Smoldering Multiple Myeloma?

The study of monoclonal serum proteins has led to the generation of two major theories: one proposing that individuals who had monoclonal proteins without any symptoms or evidence of end-organ damage have a benign condition, the other one suggesting that some individuals with asymptomatic monoclonal proteins may progress to multiple myeloma and thus are affected by a monoclonal gammopathy of undetermined significance (MGUS). Longitudinal studies of subjects with MGUS have supported the second theory. Subsequent studies have characterized and defined the existence of another precursor of multiple myeloma, smoldering multiple myeloma (SMM), intermediate between MGUS and multiple myeloma. Primary molecular events, chromosome translocations, and chromosome number alterations resulting in hyperploidy, required for multiple myeloma development, are already observed in myeloma precursors. MGUS and SMM are heterogeneous conditions with the presence of tumors with distinct pathogenic phenotypes and clinical outcomes. The identification of MGUS and SMM patients with a molecularly defined high risk of progression to MM offers the unique opportunity of early intervention with a therapeutic approach on a low tumor burden.

CAR-T Cell Therapy for T-Cell Malignancies.

Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of B-cell lymphoid neoplasia and, in some instances, improved disease outcomes. Thus, six FDA-approved commercial CAR-T cell products that target antigens preferentially expressed on malignant B-cells or plasma cells have been introduced in the therapy of B-cell lymphomas, B-ALLs, and multiple myeloma. These therapeutic successes have triggered the application of CAR-T cell therapy to other hematologic tumors, including T-cell malignancies. However, the success of CAR-T cell therapies in T-cell neoplasms was considerably more limited due to the existence of some limiting factors, such as: 1) the sharing of mutual antigens between normal T-cells and CAR-T cells and malignant cells, determining fratricide events and severe T-cell aplasia; 2) the contamination of CAR-T cells used for CAR transduction with malignant T-cells. Allogeneic CAR-T products can avoid tumor contamination but raise other problems related to immunological incompatibility. In spite of these limitations, there has been significant progress in CD7- and CD5-targeted CAR-T cell therapy of T-cell malignancies in the last few years.

CAR-T Cell Therapy in B-Cell Acute Lymphoblastic Leukemia.

Treatment of refractory and relapsed (R/R) B acute lymphoblastic leukemia (B-ALL) is an unmet medical need in both children and adults. Studies carried out in the last two decades have shown that autologous T cells engineered to express a chimeric antigen receptor (CAR-T) represent an effective technique for treating these patients. Antigens expressed on B-cells, such as CD19, CD20, and CD22, represent targets suitable for treating patients with R/R B-ALL. CD19 CAR-T cells induce a high rate (80-90%) of complete remissions in both pediatric and adult R/R B-ALL patients. However, despite this impressive rate of responses, about half of responding patients relapse within 1-2 years after CAR-T cell therapy. Allo-HSCT after CAR-T cell therapy might consolidate the therapeutic efficacy of CAR-T and increase long-term outcomes; however, not all the studies that have adopted allo-HSCT as a consolidative treatment strategy have shown a benefit deriving from transplantation. For B-ALL patients who relapse early after allo-HSCT or those with insufficient T-cell numbers for an autologous approach, using T cells from the original stem cell donor offers the opportunity for the successful generation of CAR-T cells and for an effective therapeutic approach. Finally, recent studies have introduced allogeneic CAR-T cells generated from healthy donors or unmatched, which are opportunely manipulated with gene editing to reduce the risk of immunological incompatibility, with promising therapeutic effects.

CAR-T Cell Therapy for Follicular Lymphomas.

Follicular lymphoma is the second most diagnosed lymphoma in Western Europe. Significant advancements have considerably improved the survival of FL patients. However, 10-20% of these patients are refractory to standard treatments, and most of them will relapse. The treatment of follicular lymphoma patients with multiply relapsed or refractory disease represents an area of high-unmet needing new treatments with stronger efficacy. Chimeric antigen receptor (CAR)-T cell therapy targeting B-cell antigens, such as CD19 or CD20, is emerging as an efficacious treatment for R/R follicular lymphoma patients, particularly for those with early relapse and refractory to alkylating agents and to anti-CD20 monoclonal antibodies, resulting in a high rate of durable responses in a high proportion of patients.

Effects of immediate thrombolytic treatment in imaging area on functional outcome in patients with acute ischemic stroke.

INTRODUCTION: Door-to-needle time (DNT) is an established predictor of outcome in acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT). Several strategies have been proposed to streamline in-hospital pathways, among which treatment at CT/MR bed. AIM: To explore the impact of treatment at CT/MR bed, here defined as imaging area (IA), on functional outcome in stroke patients treated with IVT alone. METHODS: All AIS patients treated with IVT alone at our center in 2020, 2021, and 2022 were included. Patients with any previous disability were excluded. The cohort was divided into two groups, depending on the treatment site. One group received IVT at IA, the other at emergency room or stroke unit (non-IA). Regression analysis assessed the association between treatment site and 3-month outcome. RESULTS: A total of 327 patients who received IVT alone were included in the analysis. One hundred thirty-three (40.7%) were in the IA group and 194 (59.3%) in the non-IA group. The groups showed similar baseline characteristics. In the IA group, DNT was 45 min shorter. Despite similar rates of functional independence (mRS 0-2), the IA group showed higher rates of excellent outcome (mRS 0-1) compared to the non-IA group (60.1% vs 42.8%, p<0.01). Immediate treatment at IA was independently associated to excellent outcome (OR 1.78 [1.03-3.08]). CONCLUSIONS: Thrombolytic treatment at IA lowers DNT and is an independent predictor of excellent outcome after AIS. Our study emphasizes the importance of immediate thrombolytic treatment at IA, soon after radiological eligibility is confirmed. Immediate treatment at IA should be a standard-of-care for AIS.

CAR-T Cell Therapy in Large B Cell Lymphoma.

Large B-cell lymphomas (LBCLs) are among the most frequent (about 30%) non-Hodgkin's lymphoma. Despite the aggressive behavior of these lymphomas, more than 60% of patients can be cured with first-line chemoimmunotherapy using the R-CHOP regimen. Patients with refractory or relapsing disease show a poor outcome even when treated with second-line therapies. CD19-targeted chimeric antigen receptor (CAR) T-cells are emerging as an efficacious second-line treatment strategy for patients with LBCL. Three CD19-CAR-T-cell products received FDA and EMA approval. CAR-T cell therapy has also been explored for treating high-risk LBCL patients in the first-line setting and for patients with central nervous system involvement. Although CD19-CAR-T therapy has transformed the care of refractory/relapsed LBCL, about 60% of these patients will ultimately progress or relapse following CD19-CAR-T; therefore, it is fundamental to identify predictive criteria of response to CAR-T therapy and to develop salvage therapies for patients relapsing after CD19-CAR-T therapies. Moreover, ongoing clinical trials evaluate bispecific CAR-T cells targeting both CD19 and CD20 or CD19 and CD22 as a tool to improve the therapeutic efficacy and reduce the number of refractory/relapsing patients.

Diagnosis and management of tandem occlusion in acute ischemic stroke.

Approximately 20-30% of patients with acute ischemic stroke, caused by large intracranial vessel occlusion, have a tandem lesion, defined as simultaneous presence of high-grade stenosis or occlusion of the cervical internal carotid artery and thromboembolic occlusion of the intracranial terminal internal carotid artery or its branches, usually the middle cerebral artery. Patients with tandem lesions have usually worse outcomes than patients with single intracranial occlusions, and intravenous thrombolysis is less effective in these patients. Although endovascular thrombectomy is currently a cornerstone therapy in the management of acute ischemic stroke due to large vessel occlusion, the optimal management of extracranial carotid lesions in tandem occlusion remains controversial. Acute placement of a stent in the cervical carotid artery lesion is the most used therapeutic strategy compared with stented balloon angioplasty and thrombectomy alone without carotid artery revascularization; however, treatment strategies in these patients are often more complex than with single occlusion, so treatment decisions can change based on clinical and technical considerations. The aim of this review is to analyze the results of different studies and trials, investigating the periprocedural neurointerventional management of patients with tandem lesions and the safety, efficacy of the different technical strategies available as well as their impact on the clinical outcome in these patients, to strengthen current recommendations and thus optimize patient care.

Intra-Arterial Thrombolysis to Improve Final Thrombolysis in Cerebral Infarction Score after Thrombectomy: A Case-Series Analysis.

Endovascular thrombectomy is the standard treatment in selected patients with acute ischemic stroke and large vessel occlusion, but continuous improvement in angiographic and clinical outcome is still needed. Intra-arterial thrombolysis has been tested as a possible rescue tool in unsuccessful thrombectomy, or as an adjuvant therapy after the endovascular procedure, to pursue complete recanalization. Here we present a case series analysis of intra-arterial alteplase administration (5 mg bolus, repeated up to 15 mg if Thrombolysis in Cerebral Infarction (TICI) scale ≥2c is not achieved) in 15 consecutive anterior circulation stroke patients after unsuccessful thrombectomy, defined as TICI score ≤2b after at least 3 passes or if unsuitable for further endovascular attempts, with the aim of improving recanalization. An improvement of final TICI score was achieved in 10 of 15 patients (66.7%). TICI score ≥2c was achieved after 5 mg intra-arterial tissue plasminogen activator (iaTPA) in 4 patients, and after 10 mg iaTPA in 5 cases. Six of 15 patients received 15 mg iaTPA: 1 of 6 showed angiographical improvement. A major effect of intra-arterial alteplase was observed for distally migrated emboli. None of the patients experienced any symptomatic hemorrhagic transformation or other major bleeding. Our report shows, in a very small cohort, a high rate of final TICI score improvement, encouraging the development of randomized controlled trials of rescue intra-arterial thrombolysis in patients with suboptimal angiographic results after mechanical thrombectomy.

Initial Experience Using the New pHLO 0.072-inch Large-Bore Catheter for Direct Aspiration Thrombectomy in Acute Ischemic Stroke.

PURPOSE: A direct aspiration, first pass technique (ADAPT) has been introduced as a rapid and safe thrombectomy strategy in patients with intracranial large vessel occlusion (LVO). The aim of the study is to determine the technical feasibility, safety, and functional outcome of ADAPT using the newly released large bore pHLO 0.072-inch aspiration catheter (AC; Phenox). MATERIALS AND METHODS: We performed a retrospective analysis of data collected prospectively (October 2019-November 2021) from 2 comprehensive stroke centers. Accessibility of the thrombus, vascular recanalization, time to recanalization, and procedure-related complications were evaluated. National Institutes of Health stroke scale scores at presentation and discharge and the modified Rankin scale (mRS) score at 90 days post-procedure were recorded. RESULTS: Twenty-five patients (14 female, 11 male) with occlusions of the anterior circulation were treated. In 84% of cases, ADAPT led to successful recanalization with a median procedure time of 28 minutes. In the remaining cases, successful recanalization required (to a total of 96%; modified thrombolysis in cerebral infarction score 2b/3) the use of stent retrievers. No AC-related complications were reported. Other complications included distal migration of the thrombus, requiring a stent-retriever, and symptomatic PH2 hemorrhage in 16% and 4%, respectively. After 3 months, 52% of the patients had mRS scores of 0-2 with an overall mortality rate of 20%. CONCLUSION: Results from our retrospective case series revealed that thrombectomy of LVOs with pHLO AC is safe and effective in cases of large-vessel ischemic stroke. Rates of complete or near-complete recanalization after the first pass with this method might be used as a new benchmark in future trials.

Dichloro(2,2'-bipyridine)copper/MAO: An Active and Stereospecific Catalyst for 1,3-Diene Polymerization.

Dichloro(2,2'-bipyridine)copper was synthesized by reacting copper dichloride with bypyridine, and its behavior, in combination with methylaluminoxane (MAO), in the polymerization of butadiene, isoprene, 2,3-dimethyl-1,3 butadiene, and 3-methyl-1,3-pentadiene was examined. The purpose of this study is to find catalytic systems that are more sustainable than those currently used for the polymerization of butadiene and isoprene (e.g., Co and Ni), but that are comparable in terms of catalytic activity and selectivity. Predominantly, syndiotactic 1,2 polybutadiene, crystalline syndiotactic 3,4 polyisoprene, crystalline syndiotactic 1,2 poly(3-methyl-1,3-pentadiene), and crystalline cis-1,4 poly(2,3-dimethyl-1,3-butadiene) were obtained in a manner similar to that observed with the analogous iron complex. As far as we know, the investigated catalytic system represents the first example of a copper-based catalyst in the field of stereospecific polymerization. Given the great availability of copper, its extremely low toxicity (and therefore high sustainability), and the similarity of its behavior to that of iron, the result obtained seems to us of considerable interest and worthy of further investigation.

De Novo and Therapy-Related Myelodysplastic Syndromes: Analogies and Differences.

The aim of our review has been to give an appropriate idea of analogies and differences between primitive MDS (p-MDS) and t-MDS throughout an accurate reviewing of English peer-reviewed literature focusing on clinical, cytogenetic, epigenetic, and somatic mutation features of these two groups of diseases. Therapy-related MDS (t-MDS) are classified by WHO together with therapy-related acute myeloid leukemia (t-AML) in the same group, named therapy-related myeloid neoplasm. However, in clinical practice, the diagnosis of t-MDS is made with the same criteria as for primitive MDS (p-MDS), and the only difference is a previous non-myeloid neoplasm. The prognosis and the consequent therapy can be established following the same criteria as for p-MDS, and the therapy is generally decided using the same criteria. We stress the possible difference in cytogenetics, mutations, and epigenetics to distinguish the two forms. Actually, there is no marker specific for t-MDS either in cytogenetics, epigenetics, or mutations; however, some alterations are also frequent in t-MDS and, in general, they induce a poorer prognosis. So, the high-risk forms in t-MDS are prevalent. The present literature data suggest classifying the t-MDS as a subgroup of MDS and introducing some parameters to evaluate the probability of previous therapy in inducing MDS. An important issue remains the patient's fitness, which strongly influences the outcome.

Some Novel Cobalt Diphenylphosphine Complexes: Synthesis, Characterization, and Behavior in the Polymerization of 1,3-Butadiene.

Some novel cobalt diphenylphosphine complexes were synthesized by reacting cobalt(II) chloride with (2-methoxyethyl)diphenylphosphine, (2-methoxyphenyl)diphenylphosphine, and 2-(1,1-dimethylpropyl)-6-(diphenylphosphino)pyridine. Single crystals suitable for X-ray diffraction studies were obtained for the first two complexes, and their crystal structure was determined. The novel compounds were then used in association with methylaluminoxane (MAO) for the polymerization of 1,3-butadiene, and their behavior was compared with that exhibited in the polymerization of the same monomer by the systems CoCl2(PnPrPh2)2/MAO and CoCl2(PPh3)2/MAO. Some significant differences were observed depending on the MAO/Co ratio used, and a plausible interpretation for such a different behavior is proposed.

Gastroesophageal Reflux Disease - Health-Related Quality of Life Questionnaire: prospective development and validation in Italian.

OBJECTIVE: To date, two questionnaires investigating the symptoms of gastroesophageal reflux disease (GERD) (Quality of Life Reflux and Dyspepsia and Reflux Disease Questionnaire) are validated in Italian, but neither of the two questionnaires was correlated with an instrumental examination. The aim of the present study is to improve the GERD-Health Related Quality of Life (HRQL) questionnaire, to evaluate the reliability and validity of its Italian translation, and its sensitivity and specificity. METHODS: A modified Italian GERD-HRQL (MI-GERD-HRQL) questionnaire was developed adding six questions investigating on regurgitation, for a total of 15 questions. The forward-backward translation process was employed to obtain a definitive from-English-to-Italian version. Data obtained from the questionnaire were compared to upper gastrointestinal endoscopy findings. RESULTS: The questionnaire was administered twice to 130 Italian-speaking patients by two different and independent raters. Cronbach's α of the first and second questionnaire was 0.944 and 0.942, respectively. Spearman correlation and inter-rater reliability were 0.923 and 0.929, respectively. Sensitivity and specificity were 73.3 and 64%, and 69.5 and 64%, respectively, for the first and second questionnaire. CONCLUSION: The MI-GERD-HRQL questionnaire proved good consistency, reliability, sensitivity and specificity in the evaluation of typical GERD symptoms.

The Impact of Covid-19 Lockdown on Stroke Admissions and Treatments in Campania.

OBJECTIVES: The enforcement of complete lockdown with home confinement has been necessary to limit SARS-CoV-2 contagions in Italy, one the most affected countries worldwide. Simultaneously, in several Emergency Departments, a reduction in cardio- and cerebrovascular presentations was noticed. This study analyses the impact of Covid-19 pandemic and lockdown measures on the incidence of stroke, in Campania, the most densely-populated region in Italy. MATERIALS AND METHODS: We retrospectively analyzed data regarding acute stroke patients presenting at 5 Campania stroke hubs, before and after the issue of lockdown in Italy on March 9th, 2020. RESULTS: Compared to the pre-lockdown, we observed a significant reduction in the number of acute reperfusion treatments in stroke (P for interact 0.001); however the global number of patients presenting with acute stroke did not significantly differ. The time to reach medical attention was significantly longer in the lockdown phase (230 versus 154 min, P 0.016). For patients who underwent acute reperfusion treatment we also observed significantly longer time-to-imaging (30 versus 40 min, P 0.0005) and a trend to longer time-to-needle (75 versus 90 min P 0.23), but not time-to-groin. CONCLUSIONS: This study showed the reduction in acute reperfusion treatments for acute ischemic stroke and the slowdown of stroke pathways, during the lockdown phase of Covid-19 pandemic, in Campania, the third-most-populous and the most-densely populated Italian Region. In the next future, the risk for high-grade disability and death, due to delayed or even avoided hospital presentation due to fear of contagion, may be high.

Survival Improvement over Time of 960 s-AML Patients Included in 13 EORTC-GIMEMA-HOVON Trials.

We report the outcomes of secondary acute myeloid leukemia (s-AML) patients included in one of 13 European Organisation for Research and Treatment of Cancer (EORTC) collaborative AML trials using intensive remission-induction chemotherapy. Among 8858 patients treated between May 1986 and January 2008, 960 were identified as having s-AML, either after MDS (cohort A; n = 508), occurring after primary solid tumors or hematologic malignancies other than MDS (cohort B; n = 361), or after non-malignant conditions or with a history of toxic exposure (cohort C; n = 91). Median age was 64 years, 60 years and 61 years in cohort A, B and C, respectively. Among patients ≤60 years and classified in the cohorts A or B (n = 367), the 5-year overall survival (OS) rate was 28%. There was a systematic improvement in the 5-year OS rate over three time periods (p < 0.001): 7.7% (95% CI: 1.3-21.7%) for patients treated before 1990 (period 1: n = 26), 23.3% (95% CI: 17.1-30.0%) for those treated between 1990 and 2000 (period 2: n = 188) and 36.5% (95% CI: 28.7-44.3%) for those treated in 2000 or later (period 3: n = 153). In multivariate analysis, male gender (HR = 1.39; p = 0.01), WBC ≥ 25 × 109/L (HR = 2.00; p < 0.0001), age 46-60 years (HR = 1.65; p < 0.001) and poor-risk cytogenetics (HR = 2.17; p < 0.0001) were independently associated with shorter OS, while being treated during period 2 (HR = 0.50, p = 0.003) or period 3 (HR = 0.43; p = 0.0008). Having received high-dose cytarabine (HD-AraC) (n = 48) in the induction chemotherapy (HR = 0.54, p = 0.012) was associated with a longer OS. In contrast, among patients >60 years of age (n = 502), the OS was dismal, and there was no improvement over time.

Bailouts During Neurointervention; Novel Techniques in Tackling Coil Migration and Premature Intravascular Detachment of Microcatheter Tip.

BACKGROUND: Intracranial vascular malformations are increasingly being treated via the endovascular route. Though generally safe, a multitude of intraprocedural complications that potentially lead to disastrous clinical outcomes may arise. It is crucial for the operators to be well versed with the various techniques that are available to overcome any procedure-specific complications. METHODS: We present 2 cases in which we encountered premature intravascular detachment of the microcatheter tip and coil migration while treating a dural arteriovenous fistula and aneurysm, respectively. We used a stentriever to remove the detached microcatheter tip and suction using the reperfusion catheter to remove the migrated coil, both techniques that have not been reported in the literature thus far. RESULTS: Detached microcatheter tip and migrated coil were successfully retrieved using a stentriever and aspiration catheter. CONCLUSIONS: These novel techniques could potentially reduce mortality and morbidity associated with neurointervention.

The Effects of Granulocyte Colony-Stimulating Factor in Patients with a Large Anterior Wall Acute Myocardial Infarction to Prevent Left Ventricular Remodeling: A 10-Year Follow-Up of the RIGENERA Study.

BACKGROUND: the RIGENERA trial assessed the efficacy of granulocyte-colony stimulating factor (G-CSF) in the improvement of clinical outcomes in patients with severe acute myocardial infarction. However, there is no evidence available regarding the long-term safety and efficacy of this treatment. METHODS: in order to evaluate the long-term effects on the incidence of major adverse events, on the symptom burden, on the quality of life and the mean life expectancy and on the left ventricular (LV) function, we performed a clinical and echocardiographic evaluation together with an assessment using the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and the Seattle Heart Failure Model (SHFM) at 10-years follow-up, in the patients cohorts enrolled in the RIGENERA trial. RESULTS: thirty-two patients were eligible for the prospective clinical and echocardiography analyses. A significant reduction in adverse LV remodeling was observed in G-CSF group compared to controls, 9% vs. 48% (p = 0.030). The New York Heart Association (NYHA) functional class was lower in G-CSF group vs. controls (p = 0.040), with lower burden of symptoms and higher quality of life (p = 0.049). The mean life expectancy was significantly higher in G-CSF group compared to controls (15 ± 4 years vs. 12 ± 4 years, p = 0.046. No difference was found in the incidence of major adverse events. CONCLUSIONS: this longest available follow-up on G-CSF treatment in patients with severe acute myocardial infarction (AMI) showed that this treatment was safe and associated with a reduction of adverse LV remodeling and higher quality of life, in comparison with standard-of-care treatment.

Expanding Indications for Flow Diverters: Distal Aneurysms, Bifurcation Aneurysms, Small Aneurysms, Previously Coiled Aneurysms and Clipped Aneurysms, and Carotid Cavernous Fistulas.

Flow diverter devices have gained wide acceptance for the treatment of unruptured intracranial aneurysms. Most studies are based on the treatment of large aneurysms harboring on the carotid syphon. However, during the last years the "off-label" use of these stents has widely grown up even if not supported by randomized studies. This review examines the relevant literature concerning "off-label" indications for flow diverter devices, such as for distal aneurysms, bifurcation aneurysms, small aneurysms, recurrent aneurysms, and direct carotid cavernous fistulas.