Federica Fiocchi

Nonalcoholic Fatty Liver Disease in HIV-Infected Patients Referred to a Metabolic Clinic: Prevalence, Characteristics, and Predictors

BACKGROUND The prevalence and predictors of nonalcoholic fatty liver disease (NAFLD) in human immunodeficiency virus (HIV)-infected highly active antiretroviral therapy-experienced patients and the association of NAFLD with risk of cardiovascular disease and subclinical atherosclerosis are unknown. METHODS We performed a cross-sectional observational study. NAFLD was defined by liver-spleen attenuation values of <1.1 on computed tomography in persons who had neither evidence of chronic viral hepatitis nor a significant history of alcohol consumption. RESULTS We enrolled 225 patients; 163 (72.4%) were men. Mean (+/-SD) HIV infection duration was 145 +/- 60 months, and mean (+/-SD) body mass index (calculated as weight in kilograms divided by the square of height in meters) was 23.75 +/- 3.59. NAFLD was diagnosed in 83 patients (36.9% of the total cohort). The following variables were significantly associated with NAFLD in univariate analyses: sex, waist circumference, body mass index, cumulative exposure to nucleoside reverse-transcriptase inhibitors, visceral adipose tissue, homeostasis model assessment of insulin resistance index, serum alanine and aspartate aminotransferase levels, and ratios of total serum cholesterol to high-density lipoprotein cholesterol. Coronary artery calcium scores and a diagnosis of diabetes were not associated with NAFLD. In multivariable logistic regression analyses, factors associated (P<0.001) with NAFLD were higher serum alanine to aspartate ratio (odds ratio, 4.59; 95% confidence interval, 2.09-10.08), male sex (odds ratio, 2.49; 95% confidence interval, 1.07-5.81), greater waist circumference (odds ratio, 1.07; 95% confidence interval, 1.03-1.11), and longer nucleoside reverse-transcriptase inhibitor exposure (odds ratio, 1.12 per year of exposure; 95% confidence interval, 1.03-1.22). CONCLUSIONS NAFLD is common among HIV-infected persons who have the traditional risk factors for NAFLD (elevations in serum alanine level, male sex, and increased waist circumference) apparent. Exposure to nucleoside reverse-transcriptase inhibitors was an independent risk factor for NAFLD, with an 11% increase in the odds ratio for each year of use.

Coronary Aging in HIV-Infected Patients

BACKGROUND Human immunodeficiency virus (HIV)-infected patients often demonstrate accelerated aging processes. We investigated whether the vascular age of a cohort of stable HIV-infected patients receiving antiretroviral therapy (ART) was increased and sought out predictors of increased vascular age. METHODS In this cross-sectional study, 400 HIV-infected patients (mean age, 48 years) attending a cardiometabolic clinic underwent cardiac computed tomography imaging to identify coronary artery calcium (CAC). Vascular age was estimated on the basis of the extent of CAC by means of previously published equations. RESULTS Increased vascular age was observed in 162 patients (40.5%), with an average increase of 15 years (range, 1-43 years) over the chronological age. In univariable analyses, chronological age, male sex, systolic blood pressure, duration of ART, fasting glucose level, fasting serum triglyceride level, total cholesterol level, low-density and high-density lipoprotein cholesterol levels, hypertension, and the presence of the metabolic syndrome were associated with increased vascular age. In multivariable linear regression analyses, current CD4+ cell count was the only predictor of increased vascular age (beta = 0.51; P = .005). CONCLUSIONS Increased vascular age is frequent among HIV-infected patients and appears to be associated with CD4+ cell count. If these findings were to be confirmed in prospective trials, a positive response to ART with an increase in CD4+ cell count may become a marker of increased risk of atherosclerosis development.

3-T MRI in the Preoperative Evaluation of Depth of Myometrial Infiltration in Endometrial Cancer

OBJECTIVE The objective of our study was to evaluate the diagnostic accuracy of 3-T MRI in determining the depth of myometrial infiltration in patients with endometrial cancer. SUBJECTS AND METHODS Fifty-two patients (43 postmenopausal) with histopathologically proven endometrial carcinoma underwent preoperative 3-T MRI. The following sequences were performed: axial T1 fast spin-echo (FSE); axial, parasagittal, and paracoronal T2 FSE; paracoronal 3D T1 inversion recovery gradient-echo after contrast administration; and parasagittal fat-suppressed T1 FSE. All patients underwent a hysterectomy. The MRI findings were compared with histopathology results. The quantity and degree of artifacts were evaluated. RESULT . MRI performed on a 3-T unit was in agreement with histopathology in assessing the depth of invasion in 86.4% (44/52) of the patients with a mean sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 83.5%, 93.9%, 77.8%, 92.2%, and 89.7%, respectively. Performance values were also assessed for single stages of myometrial infiltration. For the detection of an intramucosal lesion (MRI, 12/52; histopathology, 6/52), sensitivity was 100%; specificity, 86.9%; PPV, 50%; NPV, 100%; and accuracy, 88.5%. For the detection of myometrial infiltration that was less than 50% (MRI, 12/52; histopathology, 16/52), sensitivity was 62.5%; specificity, 94.4%; PPV, 83.3%; NPV, 85%; and accuracy, 84.6%. For the detection of myometrial infiltration that was greater than 50% (MRI, 28/52; histopathology, 30/52), sensitivity was 93.3%; specificity, 100%; PPV, 100%; NPV, 91.7%; and accuracy, 96.2%. The following artifacts were found: abdominal wall movement, nine patients (not affecting image quality); peristalsis, 16 patients (two deeply affecting, one affecting, and 13 scarcely affecting); magnetic susceptibility artifact, four patients (not affecting); chemical shift, 20 patients (four scarcely affecting and 16 not affecting); and dielectric effect, six patients (four deeply affecting and two affecting). CONCLUSION In evaluating the depth of myometrial infiltration in patients with endometrial cancer, 3-T MRI showed high diagnostic accuracy-equivalent to that of 1.5-T MRI reported in the literature. Artifacts did not significantly affect image quality.

FOLFOX6 and bevacizumab in non-optimally resectable liver metastases from colorectal cancer

Background:In patients with colorectal liver metastases (CLM) R0 resection significantly improves overall survival (OS).Methods:In this report, we present the results of a phase II trial of FOLFOX6+bevacizumab in patients with non-optimally resectable CLM. Patients received six cycles of FOLFOX6+ five of bevacizumab. Patients not achieving resectability received six additional cycles of each. A PET-CT was performed at baseline and again within 1 month after initiating treatment.Results:From September 2005 to July 2009, 21 patients were enrolled (Male/Female: 15/6; median age: 65 years). An objective response (OR) was documented in 12 cases (57.1%; complete responses (CRs): 3, partial response (PR): 9); one patient died from toxicity before surgery. Thirteen patients underwent radical surgery (61.9%). Three (23%) had a pathological CR (pCR). Six patients (46.1%) experienced minor postsurgical complications. After a median 38.8-month follow-up, the median OS was 22.5 months. Patients achieving at least 1 unit reduction in Standard uptake value (SUV)max on PET-CT had longer progression-free survival (PFS) (median PFS: 22 vs 14 months, P=0.001).Conclusions:FOLFOX6+bevacizumab does not increase postsurgical complications, yields high rates of resectability and pCR. Early changes in PET-CT seem to be predictive of longer PFS.

Chronic total coronary occlusion in patients with intermediate viability: value of low-dose dobutamine and contrast-enhanced 3-T MRI in predicting functional recovery in patients undergoing percutaneous revascularisation with drug-eluting stent

PurposeMyocardial viability was evaluated by magnetic resonance imaging (MRI) in patients with chronic total coronary occlusion (CTO) treated with a drug-eluting stent. Change in left ventricular ejection fraction (LVEF) was analysed.Materials and methodsTwenty-three patients with CTO underwent delayed-enhancement (DE) and low-dose dobutamine MRI (LD). Diastolic wall thickness (DWT), dobutamine-induced systolic wall thickening (SWT) and DE transmural extension were quantitatively assessed in vessel-related segments, calculating the contribution of viable tissue to SWT, expressed as viability index (VI)=[SWT×(100 − DE)]/100. Patients with transmural enhancement were excluded from revascularisation. At 6 months follow-up, patients underwent coronary angiography (CA) and MRI. Functional recovery was defined as a 2-mm increase in SWT.ResultsTransmural enhancement (mean DE 62.88±37.18] was present in three patients. Mean DWT, SWT, VI and DE of recanalised patients were 8.03±2.35, 2.64±1.56, 1.77±1.48 mm and 41.97±30.32. Revascularisation was successful in 14/16. Follow-up CA showed patency of treated vessels. Functional recovery was achieved in 13 patients. Functional recovery showed significant correlation with SWT (β 1,779, p=0.015), and even higher correlation with VI (β 2.032, p=0.011). LVEF improved significantly [Delta 95% confidence interval (CI) −4.47, p=0.0203).ConclusionsInvasive CTO treatment has beneficial effects on myocardial contractility that can be predicted by VI, and on LVEF.RiassuntoObiettiviValutazione mediante risonanza magnetica (RM) della vitalità miocardica in pazienti con occlusione coronarica cronica (CTO) trattati mediante stent medicati. Valutare la modificazione della frazione di eiezione (FE).Materiali e metodiVentitré pazienti con CTO sono stati sottoposti RM con contrasto e dobutamina a bassa dose. Sono stati valutati quantitativamente spessore telediastolico (DWT), telesistolico (SWT) e enhancement tardivo (DE) nei segmenti relativi al vaso occluso, calcolando il contributo del tessuto vitale a SWT, espresso come viability index (VI)=[SWT×(100−DE)]/100. Pazienti con infarto transmurale sono stati esclusi dalla rivascolarizzazione. A 6 mesi si esegue follow-up angiografico e RM. Recupero funzionale (RF) è definito come incremento di 2 mm di SWT.RisultatiEnhancement transmurale (62,88±37,18) era presente in 3 pazienti. DWT, SWT, VI e DE medi dei pazienti rivascolarizzati erano 8,03±2,35, 2,64±1,56, 1,77±1,48 mm e 41,97±30,32. Rivascolarizzazione efficace era presente in 14/16. La CA di follow-up ha mostrato pervietà di tutti i vasi trattati. Il RF è stato ottenuto in 13 pazienti. Il RF ha correlazione significativa con SWT (β 1,779, p=0,015) e VI (β 2,032, p=0,011). EF è migliorata significativamente (delta 95% CI −4,47, p=0,0203).ConclusioniIl trattamento percutaneo delle CTO ha effetti positivi sulla contrattilità miocardica, che possono essere predetti dal VI, e sulla FE.

In vivo 3 T MR diffusion tensor imaging for detection of the fibre architecture of the human uterus: a feasibility and quantitative study

OBJECTIVE The aim of this study was to investigate the feasibility of depicting fibre architecture of human uteri in vivo using 3 T MR diffusion tensor imaging (MR-DTI) with a three-dimensional (3D) tractography approach. Quantitative results were provided. METHODS In vivo 3 T MR-DTI was performed on 30 volunteers (9 Caesarean delivery). Main diffusion directions reflecting the fibre orientation were determined using sensitivity-encoding single-shot echo planar imaging with diffusion-sensitised gradients (b=600 mm(2) s(-1)) along 32 directions. A deterministic fibre-tracking algorithm was used to show in vivo fibre architecture, compared with ex vivo histological slides of cadaveric uteri. The number of fibres, the fibre density, the fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) were measured in 13 volunteers. RESULTS Anisotropy was found in most regions of normal uteri and the preferential order of uterine fibres depicted, consisting of two representative fibre directions: circular and longitudinal, as in ex vivo studies. Two-thirds of uteri with a Caesarean scar did not have the same orientation of fibres in the anterior isthmus when compared with non-scarred myometrium. Quantitative data were obtained from 13 volunteers: Caesarean-scarred uteri (n=5) showed lower fibre number and density in the scarred anterior isthmus than the nulliparous uteri (n=8). No significant differences were found in FA (0.42 ± 0.02, 0.41 ± 0.02; p=0.25) and ADC (1.82 ± 0.18 × 10(-3) mm(2) s(-1), 1.93 ± 0.25 × 10(-3) mm(2) s(-1); p=0.20). CONCLUSION Fibre architecture of the human uterus can be depicted in vivo using 3 T MR-DTI. Advances in knowledge 3 T MR-DTI can help to provide an in vivo insight of uterine anatomy non-invasively, especially in females with previous Caesarean surgery, in order to provide better management of subsequent deliveries.

A multicenter randomized study to evaluate intracoronary abciximab with the ClearWay catheter to improve outcomes with Lysis (IC ClearLy): trial study design and rationale.

Background Percutaneous coronary intervention (PCI) is a highly effective therapy for acute ST-elevation myocardial infarction. Adjunctive therapy with platelet glycoprotein (GP) IIb/IIIa inhibitor can result in increased vessel patency and improved outcomes in ST-elevation myocardial infarction patients undergoing PCI. The investigation of novel dosing and delivery strategies of this therapy may help to further improve outcomes. Methods IC-Clearly is a randomized, open-label, multicenter trial, with the purpose of evaluating the effectiveness of an intracoronary bolus dose of abciximab delivered using the ClearWay RX catheter vs. an intravenous bolus of abciximab for ST-elevation myocardial infarction with angiographically visible thrombus (thrombus grade ≥2). A total of 150 patients will be randomized 1: 1 to treatment of the culprit artery with intracoronary abciximab (75 patients) or intravenous abciximab (75 patients) in addition to a maintenance infusion regimen of abciximab administered intravenously for 12 h after PCI. The number of patients included in this study is based on the estimation of sample size needed to identify a statistically significant difference in the primary endpoints between the two groups. The primary endpoint chosen to evaluate this hypothesis is infarct size assessed by cardiac magnetic resonance. Clinical outcomes will be assessed for each patient through hospital discharge and at 30-day follow-up. Conclusion The purpose of this study is to evaluate whether an intracoronary bolus of abciximab delivered with the ClearWay RX catheter prior to the 12 h post-PCI intravenous infusion regimen of abciximab will result in significant additional clot resolution in vivo and improved myocardial perfusion when compared with an intravenous bolus of abciximab on top of the 12 h post-PCI intravenous infusion regimen of abciximab as per standard practice. The primary endpoint chosen to evaluate this hypothesis is infarct size as assessed by cardiac magnetic resonance.

3-Tesla MRI for the evaluation of myocardial viability: a comparative study with 1.5-Tesla MRI

Purpose . We compared 3-Tesla (3-T) and 1.5-Tesla (1.5-T) cardiac magnetic resonance imaging (MRI) for the assessment of myocardial viability in nearly identical experimental conditionsMaterials and methods . Thirty-five patients (mean age 63±11; 94.2% men) submitted to primary coronary angioplasty underwent both 3-T and 1.5-T cardiac MRI, which was considered the gold standard. Comparison was performed on the basis of the same viability imaging protocol, which included resting cine-MR [balanced fastfield echo (b-FFE) sequence] followed by contrastenhanced MR to evaluate perfusion and delayed enhancement (DE). We then performed functional index measurements and visual estimation of kinesis, perfusion and DE referring to a 5-point scale. Image quality was assessed on the basis of signal to noise ratio (SNR) and contrast to noise ratio (CNR)Results . We found nonsignificant differences between the two scanners ( p =NS) in measuring the functional and viability parameters. Myocardial SNR was significantly higher with 3-T MRI compared with 1.5-T MRI (61.3% gain). Even though a loss of CNR was recorded in b-FFE and in first-pass perfusion sequences (12.4% and 23.7%, respectively), on DE images, we quantified the increase of SNR and CNR of infarction of 387.8% and 330%, respectivelyConclusions . We found that 3-T MRI showed high concordance with 1.5-T MRI in the evaluation of functional and viability parameters and provided better evidence of damaged myocardiumRiassuntoObiettivo . Confrontare la risonanza magnetica (RM) cardiaca a 3 Tesla (3 T) con quella a 1,5 Tesla (1,5 T) per la valutazione della vitalità miocardica in condizioni sperimentali essenzialmente identicheMateriali e metodi . Trentacinque pazienti (età media di 63±11; 94,2% maschi) dopo essere stati sottoposti ad angioplastica primaria sono stati esaminati sia con RM cardiaca a 3 T che RM cardiaca a 1,5 T, che è stata considerata il gold standard. Il confronto è stato effettuato basandosi sullo stesso protocollo di imaging di vitalità che includeva: cine-MR a riposo (sequenza b-FFE) seguito da somministrazione di contrasto per la valutazione della perfusione e dell’enhancement tardivo (DE). È stata poi eseguita la misura degli indici funzionali e l’analisi visuale della cinesi, perfusione e dell’enhancement tardivo basandosi su una scala a 5 punti. La qualità di immagine è stata valutata sulla base del rapporto segnale-rumore (SNR) e del rapporto contrasto-rumore (CNR)Risultati . Abbiamo trovato una differenza statisticamente non significativa tra le due apparecchiature RM (p=NS) nella misurazione dei parametri funzionali e di vitalità. Il SNR miocardico è risultato significativamente più alto con lo scanner a 3 T MR rispetto a quello a 1,5 T (61,3% guadagno). Nonostante sia stata apprezzata una perdita di CNR nelle sequenze b-FFE e di perfusione al primo passaggio (12,4% e 23,7% rispettivamente), nelle immagini di enhancement tardivo abbiamo quantificato un aumento del SNR e CNR del tessuto infartuato del 387,8% e 330% rispettivamenteConclusioni . La RM a 3 Tesla ha dimostrato una alta concordanza con quella a 1,5 Tesla riguardo alla valutazione dei parametri funzionali e di vitalità con una più cospicua evidenza del miocardio danneggiato

Human immunodeficiency virus infection is associated with accelerated atherosclerosis

OBJECTIVES Cardiovascular risk is increased in HIV-infected individuals compared with the general population, making HIV disease an ideal model to investigate the pathogenesis and natural history of atherosclerosis. In this pilot study, we compared the progression of coronary artery calcium (CAC) between HIV-infected and uninfected patients. METHODS Atherosclerosis progression was assessed in 25 HIV-infected men and 13 HIV-negative controls by means of sequential CAC scans using CT. A CAC score progression ≥ 15%/year was used as a surrogate marker of increased risk of cardiovascular events. RESULTS During a median follow-up of 11 months, a CAC score increase ≥ 15%/year was detected in 14 HIV-infected patients (56%) and 4 HIV-negative individuals (31%). HIV infection, age and hypercholesterolaemia were independently associated with a CAC score increase ≥ 15%/year in an adjusted Cox regression model. CONCLUSIONS HIV infection, age and hypercholesterolaemia were independently associated with CAC progression. HIV as well as traditional risk factors contribute to accelerate atherosclerosis in HIV-infected patients.

Primary adrenal gland carcinosarcoma associated with metastatic rectal cancer: a hitherto unreported collision tumor

In this report we describe the case of a young woman with familial adenomatous polyposis who developed metastatic rectal cancer during pregnancy. At diagnosis, we decided to perform a transabdominal laparoscopic adrenalectomy, because of the high risk of bowel obstruction, and to define the origin of the adrenal gland lesion, suspected to be primary on the basis of imaging results. The histological specimen showed a collision tumor between an adrenal metastasis of a rectal tumor and a primary adrenal gland carcinosarcoma. The peculiarity of the case is due not only to its clinical presentation during pregnancy, but also to the presence of this uncommon adrenal collision tumor. A particular challenge for the clinician is to define the priority between these two tumors: the presence of two distinct and colliding aggressive neoplasms poses a problem in the choice of the best therapeutic approach, also given the impossibility to biopsy all metastatic sites. However, we decided to treat the patient as having a metastatic rectal cancer, because we had a solid histological confirmation of metastases.