Alice Ferraresi

Incidence of AIDS-defining cancers and virus-related and non-virus-related non-AIDS-defining cancers among HIV-infected patients compared with the general population in a large health district of Northern Italy, 1999-2009.

The aim of the study was to investigate the incidence of AIDS‐defining cancers (ADCs) and virus‐related and non‐virus‐related non‐AIDS‐defining cancers (NADCs) in HIV‐infected patients compared with the general population, and to assess the risk factors associated with these malignancies.

Celiac Disease With Mild Enteropathy Is Not Mild Disease

BACKGROUND & AIMS Patients with celiac disease have varying degrees of damage to the small intestinal mucosa, ranging from lymphocytic duodenosis with normal villous structure to severe villous atrophy. We assessed whether the severity of mucosal lesions was associated with clinical and laboratory features of celiac disease. METHODS We compared demographic, clinical, and laboratory characteristics among patients with celiac disease who were classified based on the severity of duodenal lesions. We analyzed data from 1408 adult patients seen consecutively at a tertiary referral center since 1990. Patients were classified as having villous atrophy (n = 1249) or as having mild enteropathy (n = 159) in the presence or absence of villous atrophy. RESULTS Similar percentages of patients with villous atrophy, vs mild enteropathy, experienced weight loss (17% vs 17%), gastrointestinal manifestations (70% vs 70%), extraintestinal manifestations (66% vs 57%), and other associated conditions (19% vs 23%). More patients with villous atrophy than patients with mild enteropathy developed osteopenia or osteoporosis (22% vs 5%; P = .0005). Greater percentages of patients with villous atrophy than those with mild enteropathy also had anemia (42% vs 29%; P = .002), folate deficiency (75% vs 64%; P = .02), hypocholesterolemia (7% vs 2%; P = .02), hypocalcemia (26% vs 13%; P = .004), or hyperparathyroidism (45% vs 29%; P = .004). CONCLUSIONS Although osteopenia, osteoporosis, and alterations in laboratory parameters are prevalent among patients with celiac disease with mild enteropathy, they are more prevalent and severe in those with villous atrophy. The prevalence of associated conditions is similar between these groups. These results indicate that celiac disease with mild enteropathy is not mild disease, but requires treatment with a gluten-free diet.

Factors That Contribute to Hypertransaminasemia in Patients With Celiac Disease or Functional Gastrointestinal Syndromes

BACKGROUND & AIMS Transaminasemia develops via different pathways in patients with celiac disease; no information is available on risk factors specifically attributable to celiac disease. METHODS We analyzed data collected from consecutive patients referred from January 1997 through December 2009 to the celiac disease clinic at the Spedali Civili of Brescia, Italy. We assessed the factors affecting hypertransaminasemia in 683 patients with celiac disease (based on serologic and biopsy analysis, cohort A; 34 ± 14 years of age) and 304 with functional syndromes (cohort B; 37 ± 13 years of age). RESULTS Hypertransaminasemia was detected in 138 patients in cohort A (20%). It was associated with malabsorption (odds ratio [OR], 2.22; P = .004), diarrhea (OR, 1.72; P = .005), and increasing severity of mucosal lesion (Marsh-Oberhuber class; OR, 1.46; P = .001) but not with body mass index (BMI) or the serum level of tissue-transglutaminase antibodies (tTG). Hypertransaminasemia was detected in 22 patients in cohort B (7%) and was associated with the World Health Organizations BMI categories (OR, 7.9; P < .001). In subsets of patients studied with the same analytical method (313 of cohort A and 188 of cohort B), the level of tTG was significantly higher in cohort A at baseline (25.2 ± 16.9 U/L aspartate aminotransferase [AST]) than in cohort B (20.6 ± 9.9 U/L AST, P < .0001) and was related to BMI in cohort B (P = .0012) but not cohort A. When patients were placed on gluten-free diets, the levels of AST decreased from 25.2 ± 16.9 U/L to 19.9 ± 6.6 U/L (P < .0001), independently of the changes of duodenal histology and tTG and correlated with BMI (P = .0007); the prevalence of hypertransaminasemia decreased from 13% to 4%. CONCLUSIONS Patients with celiac disease have a higher prevalence of hypertransaminasemia than controls (patients with functional syndromes). Hypertransaminasemia is related to the severity of the duodenal lesion and malabsorption but not BMI. By contrast, there was a positive correlation between the levels of AST and BMI in controls; this relationship was restored when patients with celiac disease were placed on gluten-free diets.

Incidence of cardiovascular events in HIV-positive patients compared to general population over the last decade: a population-based study from 2000 to 2012.

ABSTRACT Cardiovascular diseases are currently a main cause of death among people living with HIV. This population-based study aimed to investigate the incidence of cardiovascular events (CVEs) in HIV-positive people and factors associated with CVEs. We performed a retrospective cohort study of the HIV-infected patients residing in the Local Health Authority of Brescia, northern Italy, from 2000 to 2012. Incidence of CVEs events in HIV-positive patients was compared with that expected in general population living in the same area, computing standardized incidence ratios (SIRs). CVEs-associated risk factors were assessed using Cox regression analysis and competing risk model of death. About 3766 HIV-infected patients were included in the study. Over the 12-year-period, we recorded 134 CVEs: 83 (61.9%) acute myocardial infarctions (CVE type-1), and 51 (38.1%) strokes (CVE type-2). A twofold increased risk (SIR = 2.02) of CVEs was found in HIV-infected patients compared to the general population. Notably, within male patients: for CVE type-1, SIR = 1.89, for CVE type-2 SIR = 2.25; within female patients: for CVE type-1, SIR = 2.91, for CVE type-2 SIR = 2.07. Age >45 years, male gender, diabetes, and total blood cholesterol >200 mg/dl were significantly associated with CVEs incidence (for all, p < .05). These results were confirmed using the competing risk model. Our cohort study confirmed the higher incidence of CVEs in HIV-positive patients, and put emphasis on the importance of traditional cardiovascular risk factors. Overall CVE risk in HIV-positive patients was twice as high as CVE risk in general population. We found a peculiar gender distribution, with a relative risk for CVE type-1 higher in HIV-positive females, and a higher CVE type-2 risk in male patients. More studies are needed in order to support these findings and to further highlight possible gender differences in the risk of developing CVEs in HIV-positive patients.

Clinical Characteristics, Incidence, and Risk Factors of HIV-Related Hodgkin Lymphoma in the Era of Combination Antiretroviral Therapy

HIV-infected patients are at increased risk for developing HIV-related Hodgkin lymphoma (HIV-HL) despite the success of combination antiretroviral therapy (cART). To study the incidence of HIV-HL in HIV-patients with respect to the general population of Brescia, Italy, we conducted a single-center cohort study of HIV-patients followed from 1999 to 2009. The incidence of HIV-HL was compared to the incidence in the general population of Brescia using standardized incidence ratios (SIRs). Poisson analysis was used to study the association between covariates and HL. A total of 5085 HIV-patients were observed among 30,946 person-years; 30 patients developed HIV-HL. The incidence rate was 9.9 (95% confidence interval [CI], 6.7-14.1) per 10,000 person-years of follow-up. HL was substantially more frequent in HIV-patients than in the general population living in the same district area [standardized incidence rate, SIR=21.8 (95% CI, 15.33-31)]. The risk of HIV-HL tended to increase with lowering CD4+ cell counts at time of HL diagnosis [adjusted incidence relative risk (IRR) for CD4 cell count<50 cells/μL: 41.70, p<0.001]. HL risk had been elevated during the 6 months after combination antiretroviral therapy (cART) initiation (IRR: 26.65, p<0.001). Twenty-two HIV-HL cases were matched to 3280 controls. In the year preceding HIV-HL diagnosis the mean change in CD4+ cell counts between cases and controls was significantly different (-99 cells/μL for cases vs. +37 cells/μL for controls, p<0.0001). Compared with the general population, HIV-infected patients showed an increased risk for developing HL. The risk of HIV-HL increased significantly in the first months after cART initiation.

Neutrophil to Lymphocyte Ratio and Cardiovascular Disease Incidence in HIV-Infected Patients: A Population-Based Cohort Study.

Neutrophil to lymphocyte ratio (NLR) has been shown to predict occurrence of cardiovascular events in the general population. The aim of our study was to evaluate the role of NLR to predict major cardiovascular disease (CVD) events in HIV-infected subjects. We performed a retrospective cohort study of HIV-infected patients residing in the Local Health Authority (LHA) of Brescia, northern Italy, from 2000 to 2012. The incidence of CVD events in HIV-positive patients was compared with that expected in the general population living in the same area, computing standardized incidence ratios (SIRs). To evaluate the predictive role of NLR, univariate and multivariate Cox regression models were applied, computing hazard ratios (HRs). A total of 3766 HIV-infected patients (mean age 38.1 years, 71.3% males) were included (person-years 28768.6). A total of 134 CVD events occurred in 119 HIV-infected patients. A 2-fold increased risk (SIR 2.02) of CVD was found in HIV-infected patients compared to the general population. NLR levels measured at baseline and during follow-up were independently associated with CVD incidence, when also adjusting for both traditional CVD risk factors and HIV-related factors (HR 3.05 for NLR≥ 1.2). The area under the receiver operating characteristics (ROC) curve showed a modest, not statistically significant, increase, from 0.81 to 0.83, with addition of NLR to Framingham risk score model covariates. In conclusion an elevated NLR is a predictor of risk CVD in HIV-infected patients, independently from the traditional CVD risk factors.

Screening for Neurocognitive Impairment in HIV-Infected Individuals at First Contact after HIV Diagnosis: The Experience of a Large Clinical Center in Northern Italy

Neurocognitive disorders are emerging, probably underestimated, complications in HIV-infected people. The aim of the study was to assess neurocognitive profiles of newly detected HIV-infected patients. We performed an observational retrospective single-cohort study. Illiterates and patients with neurologic symptoms or previous psychiatric diagnosis were excluded. Neuropsychological profiles were assessed using a validated battery of neuropsychological tests. We included 206 patients; with males representing the majority of them (85%). Risk factors for HIV acquisition were unprotected sexual intercourse (homo/bisexual in 39.8% and heterosexual in 60.2%). Thirty-nine patients (18.9%) were previous injection drug users, while 41 (19.9%) were alcohol abusers. Mean education was 11.1 years (SD—standard deviation—3.7). A high prevalence of HIV-associated neurocognitive disorders (HAND, 47.1%) was present in HIV-infected patients: particularly, asymptomatic neurocognitive impairment (ANI) was found in 30.6%, mild neurocognitive disorder (MND) in 15% and HIV-associated dementia (HAD) in 1.5%. Male gender, low degree of education, AIDS diagnosis and gepatitis B virus (HBV) co-infection were factors independently associated with HAND in a multivariable logistic regression model. Our data suggest that patient-specific factors and AIDS diagnosis have a certain kind of impact in HAND occurrence. A complete neuropsychological screening must be recommended in all patients at HIV-infection diagnosis.

Elderly Women With Human Immunodeficiency Virus Infection: Is There an Effect of the Virus on Neuropsychological Profile?

Conflict of Interest: This article is based on Lynn Boyars’s doctoral dissertation at Walden University. Author Contributions: Boyars: study concept and design, acquisition of data, analysis, interpretation of data, preparation of manuscript. Sponsor’s Role: This material is the result of work supported by the use of facilities at the Veterans Affairs Illiana Healthcare System, Danville, Illinois. The views expressed herein are those of the author and do not necessarily reflect the views or the official policy of the Department of Veterans Affairs or the U.S. government.

PTH-111 “non Celiac Gluten Sensitivity” (ncgs) Is Uncommon In Patients Spontaneously Adhering To Gluten Free Diet (gfd), And Is Outnumbered By “fodmaps Sensitivity”

Introduction It is controversial whether symptoms in patients fulfilling the clinical criteria for NCGS1 are specifically triggered by gluten or by cereal components other than gluten and specifically FODMAPs, or are attributable to a nocebo effect2. Our aim was to test assess gluten or FODMAPs dependence of symptoms in patients diagnosed as NCGS. Methods NCGS patients referred to our Clinic were randomised to a double blind cross over study involving challenge with 10 g gluten Vs 10 g gluten free flour containing FODMAPs for 10 days each with 2 weeks wash-out in between (challenge stage). Patients were subsequently kept on a low FODMAPs diet for 8 weeks (low FODMAPs stage) Endpoints: patients were asked to indicate by symptom recurrence the gluten phase of challenge; correct identification was taken to indicate NCGS and incorrect identification accompanied by reduction of GSRS score during the low FODMAPs diet were taken to indicate FODMAPs sensitivity. Results Twenty-five patients without celiac disease (age 42+9 years, M/F = 2/23, 10 HLA DQ2/8 positive, 13 negative, 2 unknown) on strict GFD entered the study. During the challenge stage, the gluten phase was correctly identified by 8 patients thus fulfilling criteria for NCGS (4 with HLA DQ2/8). Scores for the 3 dimensions of GSRS (pain p = 0.03; indigestion p = 0.02; and diarrhoea p = 0.02) were higher in NCGS patients during the gluten than gluten free flour challenge. Twelve patients thought they were challenged gluten while on gluten free flour indicating gluten independent symptom recurrence (gluten insensitive). GSRS scores in these patients were higher (pain p = 0.004; reflux p = 0.013; indigestion p = 0.014, constipation p = 0.014) during challenge with gluten free flour than with gluten. Five patients reported mild symptoms during both phases suggesting a nocebo effect. During the low FODMAPs stage the score of indigestion dimension (comprising borborygmus, bloating, eructation, flatus) was significantly reduced (p = 0.011) in the gluten insensitive patients suggesting FODMAPs sensitivity. There was no significant change in the 5 dimensions of the GSRS in NCGS patients. Conclusion We conclude that the population of patients reporting intolerance to gluten containing diet is a mixed population of NCGS and of FODMAPs sensitive patients. NCGS is uncommon and is outnumbered by FODMAPs sensitivity in patients spontaneously adhering to GFD. Distinction between these 2 conditions is clinically relevant in relation to dietary counselling. References 1 Ludvigssonet al. Gut 2013;62:43 2 Gibson and Muir. Gastroenteroloy 2013;145; 693 Disclosure of Interest None Declared.

Sa1279 “Non Celiac Gluten Sensitivity” (NCGS) Is Uncommon in Patients Spontaneously Adhering to Gluten Free Diet (GFD) Without Medical Necessity

Enteropathy-associated T-cell lymphoma (EATL) is a rare intestinal lymphoma that arises from intraepithelial lymphocytes. Clinical outcome of patients with EATL is very poor, due to chemotherapy-resistance and high relapse rates. Therefore, new therapeutic options for EATL are urgently needed. Many studies in other types of lymphoma have shown that inhibition of apoptosis may cause chemotherapy-resistance and that restoration of defective apoptosis can induce cell death in these lymphomas. Preliminary data in EATL samples have demonstrated an increased expression of a fraction of NFκB target genes, suggesting upregulation of NF-κB activity in EATL tumor cells. The proteasome inhibitor bortezomib inhibits NF-κB activity and can induce apoptosis via upregulation of the pro-apoptotic BH3only protein Noxa. In the present study, we evaluated if the intrinsic apoptosis pathway is disrupted in EATL and if bortezomib can restore apoptosis in cultured EATL cells. Lasercapture microdissection was applied to 19 frozen EATL samples to obtain purified tumor cells for RNA isolation. Intraepithelial lymphocytes (IEL) of healthy controls were obtained from fresh duodenal biopsies and isolated by FACS cell sorting. RT-MLPA analysis revealed that expression of the pro-apoptotic BH3-only gene Noxa was significantly downregulated in EATL cells compared to healthy donor IEL. Treatment with bortezomib resulted in induction of apoptosis in all EATL samples tested. The lethal dose (LD50) varied between 5 nM and 15 nM after 36 and 48 hours of incubation. Bortezomib-induced cell death in EATL cells was caspase-9 mediated. mRNA and protein expression analyses showed upregulation of Noxa after incubation with bortezomib. Downregulation of Noxa using siRNA analysis decreased bortezomib-induced apoptosis in EATL cells. In conclusion, our study showed that bortezomib induces apoptosis by upregulation of Noxa in EATL cells. Therefore, bortezomib should be considered as a potential drug in the treatment of patients with EATL to improve their prognosis.