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  • 1
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 4400-4400
    Abstract: Background Optimization of pre-transplant risk assessment is a crucial issue to improve the allo-HSCT decision making process. Actually 3 major algorithms are in use in clinical practice: the EBMT risk score, the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) score and - more recently introduced - the refined Disease Risk Index (DRI). DRI was defined to calibrate HSCT outcome across studies and centers. It was developed as a tool to assign patients into risk groups based on disease type and status at the time of transplantation. The aim of the DRI is to provide a robust tool that can be used for prognostication, for the analysis and interpretation of retrospective data, whether conducted in single-center, multicenter, or registry settings, or within the context of the federally mandated center outcome reporting. The DRI can also be used for the stratification of patients entering prospective HCT clinical trials. DRI is not a fixed tool but instead it was conceived to be refined by the transplant community as new information becomes available. Here we are presenting the results of a retrospective study designed to evaluate the 3 aforementioned score in stratification and prognostication of transplant outcome after a haploidentical HSCT (haplo-HSCT). Patients and Methods We included 220 adult patients (pts - 138 male, 82 female) who underwent a haplo-HSCT for hematologic malignancies, between 2006 and 2014 and were reported to our Institutional database. Risk assessment score and outcome analysis included all consecutive pts receiving an haplo-HSCT as 1st allogeneic transplantation. Pts receiving haplo-HSCT as 2nd or 3rd HSCT were excluded from the present analysis. Median age was 49 years (range, 15-77). The cohort included a broad representation of diseases (138/220 acute leukemia, 30 Hodgkin lymphoma); 62 pts were in complete remission at transplant, 158 were presenting active disease. Conditioning regimens mostly rely upon the combination of treosulfan plus fludarabine (201/220) and total body irradiation (range 200 - 400 cGy) was utilized in 52 patients. GVHD prophylaxis consisted mostly of an mTor inhibitor (rapamycin) combined with mycophenolate mofetil. The majority of patients received peripheral blood stem cells from a family haploidentical donor as stem cell source, while only 4 patients received bone marrow transplant. A written consent was given by pts allowing the use of medical records for research in accordance with the Declaration of Helsinki. Results The median follow-up for survivors was 37 months (r 6-107). The overall survival (OS) at 2-y was 35% and the transplant related mortality at 100-days 23%. The 2y OS according to EBMT / HCT-CI / DRI risk score are reported in table 1.a and figure 1. The evaluation of the HCT-CI impact after DRI stratification was able to show a significant difference in outcome showing better survival for pts with low DRI score and low HCT-CI score as expected (table 1.b). Discussion Refined DRI score and HCT-CI score predict survival after haplo-HSCT. The integrated application of refined DRI and HCT-CI may improve the definition of transplant eligibility for pts candidate to allogeneic HSCT form alternative donors including family haploidentical source. Table 1a. EBMT score 0-3 % pts 4-5 %pts 〉 5 %pts p 51% 17 34% 51 27% 32 0.07 HCT-CI score 0-2 3-4 〉 /= 5 48% 59 36% 31 0% 10 0.0001 DRI score Low-Intermediate High Very-High 61% 32 27% 51 5% 17 0.0001 Table 1b. HCT-CI 0-4 HCT-CI 〉 /=5 p DRILow-Intermediate 64% 0% 0.0001 DRIHigh-Very High 29% 0% Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
    detail.hit.zdb_id: 1468538-3
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  • 2
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 65, No. 11 ( 2017-11-13), p. 1884-1896
    Abstract: Gram-negative bacteremia (GNB) is a major cause of illness and death after hematopoietic stem cell transplantation (HSCT), and updated epidemiological investigation is advisable. Methods We prospectively evaluated the epidemiology of pre-engraftment GNB in 1118 allogeneic HSCTs (allo-HSCTs) and 1625 autologous HSCTs (auto-HSCTs) among 54 transplant centers during 2014 (SIGNB-GITMO-AMCLI study). Using logistic regression methods. we identified risk factors for GNB and evaluated the impact of GNB on the 4-month overall-survival after transplant. Results The cumulative incidence of pre-engraftment GNB was 17.3% in allo-HSCT and 9% in auto-HSCT. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most common isolates. By multivariate analysis, variables associated with GNB were a diagnosis of acute leukemia, a transplant from a HLA-mismatched donor and from cord blood, older age, and duration of severe neutropenia in allo-HSCT, and a diagnosis of lymphoma, older age, and no antibacterial prophylaxis in auto-HSCT. A pretransplant infection by a resistant pathogen was significantly associated with an increased risk of posttransplant infection by the same microorganism in allo-HSCT. Colonization by resistant gram-negative bacteria was significantly associated with an increased rate of infection by the same pathogen in both transplant procedures. GNB was independently associated with increased mortality at 4 months both in allo-HSCT (hazard ratio, 2.13; 95% confidence interval, 1.45–3.13; P 〈 .001) and auto-HSCT (2.43; 1.22–4.84; P = .01). Conclusions Pre-engraftment GNB is an independent factor associated with increased mortality rate at 4 months after auto-HSCT and allo-HSCT. Previous infectious history and colonization monitoring represent major indicators of GNB. Clinical Trials registration NCT02088840.
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
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    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2017
    detail.hit.zdb_id: 2002229-3
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  • 3
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 3492-3492
    Abstract: Introduction Pre-transplant risk assessment is a crucial issue to improve the HCT decision-making process. Several transplant-related models have been designed to optimize decision-making about suitable candidates for allogeneic HCT. The refined Disease Risk Index (DRI) was developed to stratify disease risk acrosshistologiesand HCT regimens. However, few recipients of haploidentical HCT were originally included in the DRI study cohorts. In 2015 a first large cohort of non-myeloablativehaploidentical HCT with post-transplant cyclophosphamide (PTCy) confirmed the validity of DRI also in this setting. Beside this, in the past few years the novel composite end point of GVHD-free, relapse-free survival (GRFS) after HCT spreads out. GRFS acknowledge that both survival and rates of grade 3-4 acute GVHD, chronic GVHD requiring systemic treatment, relapse, or death are clinically meaningful. GRFS therefore represents ideal recovery from HCT and a measure of cure without ongoing morbidity. Methods We analyzed risk-stratified GRFS according to the refined DRI in haploidentical HCT at our Center, where it was exploited - since 2006 - asirolimus-based,calcineurininhibitor-free prophylaxis of GvHD to allow the safe infusion of unmanipulated haploidentical HCT. We analyze data collected between 2006 and 2014 including 207 adult pts. Data were prospectively collected in Institutional database. A written consent was given by pts allowing the use of medical records for research in accordance with the Declaration of Helsinki. All consecutive pts receiving a haplo HCT as 1st allogeneic transplantation were included - pts receiving haplo HCT as 2nd or 3rd HCT were excluded from the present analysis. Results Baseline characteristics of the 207 pts are outlined in table 1. With 4-year median follow-up, 4-year probabilities of transplant related mortality (TRM),relapse, progression-free survival (PFS), and overall survival (OS) were 25,8%, 42,5%, 31,7%, and 34,4%, respectively. Day-100 cumulative incidence of grade II-IV and III-IV acute graft-versus-host-disease (GvHD) were 30,1% and 15,5% respectively. The 4-year cumulative incidence of chronic GvHD was 33,5% (moderate-severe chronic GvHD 26,2%). Considering the composite end point of GRFS, for the entire population the 4-year GRFS was 17,8%. By refined DRI group, low-intermediate (n 69), high (n 105), and very high (n 33) risk groups had 4-year GRFS estimates of 31,1%, 13,7%, and 3,0% (p 〈 .0001), with corresponding 4-year OS estimates of 56,7%, 28,9%, and 6,1% (p 〈 .0001). On a multivariable Cox model we considered as covariates age, host/donor sex mismatch, host/donor CMV status, stem cell source, conditioning intensity, GvHD prophylaxis ATG-based versusPTCy-based, DRI stratification, HCT Comorbidity Index Score (HCT-CI). On multivariable analyses, the DRI was statistically significantly associated with GRFS, OS, PFS, relapse, TRM and grade II to IV acute GvHD (ref table 2). HCT-CI was statistically significantly associated with GRFS, OS, PFS and TRM. Conditioning intensity was associated with PFS and relapse, while GvHD prophylaxis (PTCyvs ATG) was only associated with OS. Interestingly no risk factors were clearly emerging for chronic GvHD. Conclusions The combination of a refined DRI and GRFS provide a valid tool to improve the HCT decision-making process and will help optimize patient outcomes. Disclosures Ciceri: MolMed SpA: Consultancy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
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  • 4
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 1960-1960
    Abstract: Abstract 1960 BACKGROUND: Human herpesvirus 6 (HHV-6) is increasingly recognized as an opportunistic and potentially life-threatening pathogen in recipients of allogeneic Hematopoietic Stem Cell Transplantation (HSCT). Reported clinical manifestations of HHV-6 infection in transplanted patients are skin rash, interstitial pneumonia, bone marrow suppression and encephalitis. Moreover, an increasing number of clinical reports suggest that HHV-6 can facilitate the occurrence of other severe clinical complications of allogeneic HSCT, including Graft-versus-Host Disease (GvHD), ultimately increasining transplant-related mortality. Still, the actual incidence of HHV-6 infection in recipients of HSCT and the causative link between infection and clinical complications remain elusive, mostly due to the small and heterogeneous patient cohorts analyzed to date. METHODS: From January 2009 to July 2011, we retrospectively evaluated 43 consecutive adult patients (median age 51 years) who developed positivity to HHV-6 after allogeneic HSCT for high-risk hematological malignancies. Stem cell donor was for 30 patients family haploidentical, for 5 an HLA identical sibling, and for 8 an unrelated volunteer (1 of which cord blood). The viral load was determined by quantitative PCR in cell-free body fluids such as plasma, bronchoalveolar lavage, cerebrospinal fluid, bone marrow aspirates or in gastrointestinal biopsies. At the time of positivity all patients were receiving acyclovir as viral prophylaxis except 5. Sixteen patients had clinical acute GvHD at time of HHV-6 positivity (grade III-IV in 14), and 33 were profoundly immunosuppressed with variable association of 2–4 immunosuppressive drugs (steroids included). Moreover concomitant CMV positivity was detected in 11 patients, while a severe neutropenia in 12. RESULTS: Median time from allogeneic HSCT to HHV-6 reactivation was 36 days (range: 7–625). In 19 patients HHV-6 was detected in plasma, with a median viral load of 19,454 cp/mL (34-4,524,600); 15 had concomitant fever, 5 skin rash of new onset, 4 impaired liver function, and 5 developed cytopenia subsequently to the infection. In 7 patients HHV-6 was detected in the bone marrow: the median viral load was 163'800 cp/mL (568-1'552'982). In 8 patients, all febrile, HHV-6 was observed in bronchoalveolar lavage samples with a median of 4'149 cp/mL (85–39250). In 16 patients, 10 with documented gut aGvHD, 11 with diarrhoea, HHV-6 was detected in gastrointestinal biopsies with a median of 7'510 cp/mL (120-4'524'600). HHV-6 was found in cerebrospinal fluid in 4 cases (all within 30 days after HSCT); the median viral load was 29'352 cp/mL (4'508-1'552'982); all these patients experienced encephalitis with confusion and anxiety, 2 suffered seizures and 3 showed abnormal findings on brain MRI. Amongst patients with organ localizations of HHV-6 only 28% had concomitant plasma positivity. HHV-6 positivity led to antiviral pharmacological treatment only when associated with clinical manifestations (n=21), using as first choice therapy foscarnet. Amongst the total 43 patients with documented HHV-6 positivity 11 completely solved the clinical event, whereas 19 (44%) died. CONCLUSIONS: HHV-6 infection/reactivation is associated with high morbidity and mortality in patients who undergo allogeneic HSCT. HHV-6 infection typically occurred close to the time of neutrophil engraftment. HSCT from an HLA-mismatched donor and steroid administration were associated with increased risk of active HHV-6 infection. Development of encephalitis was associated with high HHV-6 viral load. The regular monitoring of HHV-6 DNA in allogeneic HSCT recipients, using a real-time PCR assay, may be useful for identifying active HHV-6 infection and for the introduction of a pre-emptive treatment, possibly reducing the incidence of the most severe clinical complications. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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  • 5
    In: Minerva Cardioangiologica, Edizioni Minerva Medica, Vol. 68, No. 4 ( 2020-10)
    Type of Medium: Online Resource
    ISSN: 0026-4725 , 1827-1618
    Language: English
    Publisher: Edizioni Minerva Medica
    Publication Date: 2020
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  • 6
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 4921-4921
    Abstract: Abstract 4921 BACKGROUND: Febrile neutropenia and sepsis are frequent and life-threatening complications in patients with hematological malignancies. Prompt administration of appropriate antimicrobials is crucial to decrease the high morbidity and mortality rates of these conditions. Blood cultures (BC) identify a pathogen in only 20 to 30% of febrile episodes, with even lower sensitivity in patients already receiving antibiotics at time of sampling. Moreover the culturing and pathogen identification process is lengthy, postponing the start of a pathogen-targeted treatment, a particularly relevant issue when highly aggressive or rare agents are involved. Thereby the setup of molecular tools able to promptly recognize pathogens causing sepsis even despite ongoing antimicrobial therapy is of potential clinical relevance. METHODS: We assessed the diagnostic usefulness of the LightCycler SeptiFast test (SF), a PCR-based multiplex assay which can be performed on peripheral blood in hematological patients. In this study, blood samples from febrile oncohaematological patients were tested by traditional blood culture (BacT/Alert 3D; bioMerieux) and by a novel commercial real-time PCR assay (LightCycler SeptiFast; Roche Molecular Systems) performed concomitantly at the onset of febrile neutropenia. RESULTS: A total of 869 blood samples were collected from 273 consecutive patients treated for febrile neutropenia at the San Raffaele Hematology Unit over the last three years (July 2009–July 2011). Out of the total 869 episodes examined, positive results were detected in 246 samples by SF (28.3%), and in 143 by BC (16.4%). Together, the two methods identified a total of 345 microorganisms in 312 (36%) episodes: Gram-positive bacterial species (74%), Gram-negative bacterial species (23%), and fungal species (3%). Concordance between the two methods was 73%, mainly due to samples that tested negative by culture but positive using the molecular approach (54% of the total positive samples). The cases positive by SF alone were mostly samples from patients with initial concordant results on samples harvested before the administration of a specific antimicrobial therapy, or, importantly, sample positive for a clinically relevant agent such as Aspergillus fumigatus, which is hard to detect by the traditional approaches. CONCLUSION: The LightCycler SeptiFast test gives new insights into the natural history of infection and in the development of new algorithms for the diagnosis of sepsis in critical patients. Using SF combined with BC improves microbiological documentation in febrile neutropenia particularly in persistent fever despite antibacterial therapy, when a nonresponding bacterial infection or an invasive fungal infection is suspected; results of SF may lead to a more targeted antibiotic therapy early after the onset of fever. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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  • 7
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 2498-2498
    Abstract: Introduction Haematopoietic stem cell transplantation (HSCT) is the only curative option for patients (pts) affected by high-risk haematological diseases (HRHD). However, the availability of a match donor is still an unmet-medical need. Recently alternative donor transplantations have been broadly exploited, reaching results similar to transplants from a well match donor. Anyway, whoever the donor is, the most important complication remains Graft-versus-Host Disease (GvHD). Aim of the study We evaluated incidence, characterization, stratification, treatment, treatment response and outcome at medium and long-term follow-up for both acute (a-) and chronic (c-) GvHD in haploidentical setting. We also evaluated the impact of the NIH consensus criteria on GvHD in a routine clinical application to confirm their feasibility in daily practice and not only in clinical trials use. Methods A population of 257 pts was selected from our Institutional database on the basis of their having an HRHD with indication to allogeneic HSCT and having received a HSCT from an haploidentical family donor without exclusion. HSCT were performed between January 2004 and December 2013 at our Center. No distinction between first HSCT or subsequent one was made, all consecutive haploidentical HSCT were captured. Results Time of median follow-up was 10 months; 1-year overall-survival (OS) was 46%, with better outcome for pts transplanted in complete remission (p 0.0001) confirming disease status as the leading factor for overall outcome. Transplant related mortality was estimated to be 30% at 1 year and the leading cause of death was infections. The 6-months a-GvHD incidence was 45% (119/257) - median day of presentation 21 post HSCT (range 8-89). Late-onset a-GvHD was documented in 15 pts. Grade I GvHD was documented in 33 pts (27.7%), grade II in 44 (37%), grade III-IV in 36 (30.3%) – 6 not evaluable. Skin was the most frequently involved organ (77.3%), both as single manifestation or combined. One-hundred and five pts received a first line therapy based on high-dose prednisone (2mg/Kg) and 37/105 completely abrogated the a-GvHD. At a 3-months evaluation 46% of affected pts showed complete resolution of a-GvHD, while the mortality rate was 29%. C-GvHD affected 69/257 pts and 1-year risk of onset was 25% - median day of presentation was 139 post HSCT (range 40-809) and 36/69 pts were off immunosuppressive therapy (52.3%) at presentation. According to onset presentation 53.7% were de novo, 24.6% progressive and 18.8% quiescent GvHD. Forty-one pts (59.5%) presented at declaration with overlap features. The most frequent involved organ was skin (grade I to III), as reported in 53 pts (76.8%). Skin lesions were usually accompanied with mouth lesions (35 pts – 50.7%), liver (23 pts – 33.3%) or eyes (27 pts – 39.1%) dysfunctions. The median number of involved organs was 3 (range 1-7). Mild c-GvHD was diagnosed in 10 pts (14.5%), who received topical therapy. Fifty-nine pts – diagnosed with moderate (32, 46.4%) or severe (27, 39.1%) - received a systemic treatment for c-GvHD: prednisone 1 mg/Kg alone or 0,5 mg/kg plus mTOR- or calcineurin-inhibitor for pts that were not likely to tolerate high dose steroid due to comorbidity (namely active infections, diabetes, cardiovascular diseases). At a 12-months evaluation the overall response was 48% (complete resolution 25%, partial resolution 23%), while the mortality rate was 36%. The Landmark analysis of OS at 3 months after HSCT shows that a-GvHD affected pts had a worse outcome (p= 0,068), on the contrary the Landmark analysis of OS at 18 months shows that c-GvHD did not associate with a worse outcome (p ns) but the follow up is still short. Confirming previous reports, overlap c-GvHD was related to worse survival in comparison with classic c-GvHD (p 0.0098). Conclusion Haploidentical HSCT is a valid and feasible option for pts in need of a transplant. GvHD is manageable after haploidentical HSCT, as in full matched setting. Better knowledge and insight in a/c-GvHD are providing advance in improving pts outcome. The NIH-consensus criteria are manageable in daily clinical practice and able to translate in a tailored approach to GvHD with benefit on general outcome. Further advance in the development of specific biomarkers for GvHD will provide additional crucial information for management, diagnosis and prognostication in GvHD. Figure 1 Figure 1. Disclosures Bonini: MolMed S.p.A.: Consultancy. Bordignon:MolMed: Employment.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
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  • 8
    In: Current Neuropharmacology, Bentham Science Publishers Ltd., Vol. 19, No. 10 ( 2021-10-18), p. 1760-1779
    Abstract: Patients with Borderline Personality Disorder (BPD) manifest affective and behavioral symptoms causing personal distress, relationship difficulties, and reduced quality of life with global functioning impairment, mainly when the disease takes an unfavorable course. A substantial amount of healthcare costs is dedicated to addressing these issues. Many BPD patients receive medications, mostly those who do not respond to psychological interventions. Objective: Our aim was to assess the efficacy of the most used strategies of pharmacological interventions in BPD with a comprehensive overview of the field. Methods: We searched the PubMed database for papers focused on the most used psychotropic drugs for BPD. We included randomized controlled trials and open studies in adult patients with BPD, focusing on the efficacy and tolerability of single classes of drugs with respect to specific clinical presentations that may occur during the course of BPD. Results: Specific second-generation antipsychotics (SGAs) or serotonergic antidepressants can be effective for different core symptoms of BPD, mainly including mood symptoms, anxiety, and impulse dyscontrol. Some atypical antipsychotics can also be effective for psychotic and dissociative symptoms. Specific antiepileptics can be useful in some cases in treating different BPD symptoms, mainly including mood instability, impulsiveness, and anger. Conclusions: No medication is currently approved for BPD, and clinicians should carefully assess the benefits and risks of drug treatment. Further studies are needed to identify specific personalized treatment strategies, also considering the clinical heterogeneity and possible comorbidities of BPD.
    Type of Medium: Online Resource
    ISSN: 1570-159X
    Language: English
    Publisher: Bentham Science Publishers Ltd.
    Publication Date: 2021
    detail.hit.zdb_id: 2119376-9
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  • 9
    In: Journal of Cardiovascular Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 21, No. 3 ( 2020-03), p. 182-191
    Abstract: Since 2002, transcatheter aortic valve implantation (TAVI) has revolutionized the treatment and prognosis of patients with aortic stenosis. A preprocedural assessment of the patient is vital for achieving optimal outcomes from the procedure. Retrospective ECG-gated cardiac computed tomography (CT) today it is the gold-standard imaging technique that provides three-dimensional images of the heart, thus allowing a rapid and complete evaluation of the morphology of the valve, ascending aorta, coronary arteries, peripheral access vessels, and prognostic factors, and also provides preprocedural coplanar fluoroscopic angle prediction to obtain complete assessment of the patient. The most relevant dimension in preprocedural planning of TAVI is the aortic annulus, which can determine the choice of prosthesis size. CT is also essential to identify patients with increased anatomical risk for coronary artery occlusion in Valve in Valve (ViV) procedures. Moreover, CT is very useful in the evaluation of late complications, such as leakage, thrombosis and displacements. At present, CT is the cornerstone imaging modality for the extensive and thorough work-up required for planning and performing each TAVI procedure, to achieve optimal outcomes. Both the CT procedure and analysis should be performed by trained and experienced personnel, with a radiological background and a deep understanding of the TAVI procedure, in close collaboration with the implantation team. An accurate pre-TAVI CT and post-processing for the evaluation of all the points recommended in this review allow a complete planning for the choice of the valve dimensions and type (balloon or self-expandable) and of the best percutaneous access.
    Type of Medium: Online Resource
    ISSN: 1558-2027 , 1558-2035
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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  • 10
    In: European Journal of Neurology, Wiley, Vol. 31, No. 1 ( 2024-01)
    Abstract: Hereditary transthyretin amyloidosis (ATTRv) is a life‐threatening disease caused by mutations in the gene encoding transthyretin ( TTR ). The recent therapeutic advances have underlined the importance of easily accessible, objective biomarkers of both disease onset and progression. Preliminary evidence suggests a potential role in this respect for neurofilament light chain (NfL). In this study, the aim was to determine serum NfL (sNfL) levels in a late‐onset ATTRv population and evaluate whether it might represent a reliable biomarker of disease onset (i.e., ‘conversion’ from the asymptomatic status to symptomatic disease in TTR mutation carriers). Methods In all, 111 individuals harbouring a pathogenic TTR variant (61 symptomatic ATTRv patients and 50 presymptomatic carriers) were consecutively enrolled. Fifty healthy volunteers were included as the control group. Ella™ apparatus was used to assess sNfL levels. Results Serum NfL levels were increased in ATTRv patients compared to both presymptomatic carriers and healthy controls, whilst not differing between carriers and healthy controls. An sNfL cut‐off of 37.10 pg/mL could discriminate between asymptomatic and symptomatic individuals with high diagnostic accuracy (area under the curve 0.958; p 〈 0.001), sensitivity (81.4%) and specificity (100%). Conclusions Serum NfL seems to be a promising biomarker of peripheral nerve involvement in ATTRv amyloidosis and might become a reliable, objective measure to detect the transition from the presymptomatic stage to the onset of symptomatic disease. Further longitudinal studies are needed to confirm such a role and determine whether it could equally represent a biomarker of disease progression and response to therapy.
    Type of Medium: Online Resource
    ISSN: 1351-5101 , 1468-1331
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2024
    detail.hit.zdb_id: 2020241-6
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