Malignant melanoma in HIV: Epidemiology, pathogenesis, and management.

People affected by immunodeficiency, and especially those infected by HIV, are burdened by a higher risk of developing malignancies. It has been estimated that the incidence of melanoma in HIV-infected people is 2.6-fold higher than in uninfected ones. In this group of patients, melanoma shows a more aggressive phenotype and poorer survival rates compared to HIV-negative people. Standard guidelines of diagnosis and care do not exist yet. Studies suggest high index of suspicion and a low threshold for biopsy in HIV-positive patients regardless of their CD4+ count and the use of standard surgical margins for re-excision procedures. In case of diagnosis of melanoma in HIV-positive patients, a thorough search for metastatic disease is recommended because of the more aggressive course of this cancer in HIV-positive patients. Moreover, to rapidly find out any recurrence or metastatic disease after treatment, these patients need a close follow-up, every 3 months, for the first 2 years and at least twice yearly thereafter. Although surgery remains the main therapeutic option, application of immune checkpoint-based immunotherapy is being studied and seems to be promising. The aim of this review is to present the current knowledge and future options for melanoma diagnosis and treatment in people living with HIV.

Is it Safe and Cost Saving to Defer the CD4+ Cell Count Monitoring in Stable Patients on Art with More than 350 or 500 cells/µl?

BACKGROUND: CD4+ lymphocyte cell count represents the main immunological marker used to monitor HIV infection. However, frequent monitoring may be unnecessary, could cause anxiety to the patient as well as burdening healthcare with extra expenses. OBJECTIVES AND METHODS: A two-step retrospective (safety and cost-saving) analysis was performed to evaluate the probability of maintaining a safe number of more than 350 CD4+ cells/µl in HIV-positive subjects under treatment during a three-year follow up and secondarily to estimate in real life the cost of the CD4+ determinations in a 3 years period, speculating on possible cost-saving strategies. The safety analyses was conducted with Kaplan-Meyer method considering: 1) all patients independently from their viral load (VL); 2) patients with 500 > CD4+ ≥ 350 cells/µl versus (vs) CD4+ ≥ 500 cells/µl at baseline; 3) patients with VL < 20 copies/ml vs VL > 20 copies/ml. The cost-saving analysis measuring the costs of CD4+ determinations was calculated from April 1, 2013, to March 31, 2016. RESULTS: In the safety analysis, 253 subjects were enrolled. The median CD4+ count was 623 (489-805) cells/µl. Subjects maintaining ≥ 350 cells/µl in the first, second, and third year were respectively 238 (94.1%), 229 (90.5%), and 226 (89.3%), independently from VL. Within subjects with ≥ 350 CD4+/µl vs. ≥ 500 CD4+/µl at baseline, those who maintained ≥ 350 cells/µl until the third year were respectively 241 (95.3%) and 158 (98.1%). The probability of maintaining these values in the third year was 89.3% for those who had CD4+ ≥ 350/µl at baseline and 98.1% for those who had CD4+ ≥ 500/µl. This probability was around 90% vs. 99% for subjects with HIV-RNA above or below 20 copies/ml. In the real-life cost saving analysis, we evaluated subjects with a stable value or more than 500 CD4+ (respectively 343, 364 and 383 in the first, second and third period). We observed mean value of about two determinations patient/year (2.41 in 2013/2014; 2.32 in 2014/2015; 2.18 in 2015/2016), with a significant decrease between the first and the last period (p<0.001). The mean cost patient/year was €101.51 in the first year, €97.61 in the second, €92.00 in the third (p<0,001). Assuming to extend these procedures to all our patients with stable CD4+ cells/µl and monitoring CD4+ cell count once in a year, we were able to obtain an overall saving of €19,152/year. CONCLUSIONS: A very high percentage of subjects maintained a high and safe number of CD4+ cells (>350 cells/µl) during a three-year follow-up. It could be possible to save up to 66% of the costs by reducing the number of CD4+ count determinations in a year, to have other favorable consequences as well, releasing new resources for patient management.

Is Transient Elastography Needed for Noninvasive Assessment of High-Risk Varices? The REAL Experience.

INTRODUCTION: The Baveno VI consensus guidelines and an expanded algorithm suggest that transient elastography (TE) and platelet (PLT) count can be used to identify patients with cirrhosis who can avoid esophagogastroduodenoscopy (EGD). The primary aims of this study were to assess the ability of a simple algorithm, which uses only laboratory parameters, to predict medium/large esophageal varices (EV) in patients with hepatitis C virus (HCV) and cirrhosis from the Rete Sicilia Selezione Terapia-HCV (RESIST-HCV) cohort and to compare the performance of the algorithm with Baveno VI and Expanded Baveno VI criteria. The secondary aim was to assess the role of TE in ruling out large EV. METHODS: In total, 1,381 patients with HCV-associated cirrhosis who had EGD and TE within 1 year of starting treatment with direct-acting antivirals were evaluated. Using multivariate logistic analysis, laboratory variables were selected to determine which were independently associated with medium/large EV to create the RESIST-HCV criteria. These criteria were tested in a training cohort with patients from a single center (Palermo) and validated with patients from the 21 other centers of the RESIST-HCV program (validation cohort). RESULTS: In the entire cohort, medium/large EV were identified in 5 of 216 patients (2.3%) using the Baveno VI criteria and 13 of 497 patients (2.6%) using the Expanded Baveno VI criteria. PLT count and albumin level were independently associated with medium/large EV. The best cut-off values were a PLT count greater than 120 × 10 cells/µL and serum albumin level greater than 3.6 g/dL; negative predictive values (NPVs) were 97.2% and 94.7%, respectively. In the training cohort of 326 patients, 119 (36.5%) met the RESIST-HCV criteria and the NPV was 99.2%. Among 1,055 patients in the validation cohort, 315 (30%) met the RESIST-HCV criteria and the NPV was 98.1%. Adding TE to the RESIST-HCV criteria reduced the avoided EGDs for approximately 25% of patients and the NPV was 98.2%. DISCUSSION: The "easy-to-use" RESIST-HCV algorithm avoids EGD for high-risk EV screening for more than 30% of patients and has the same performance criteria as TE. Using these criteria simplifies the diagnosis of portal hypertension.

HIV-associated psoriasis: Epidemiology, pathogenesis, and management.

People living with HIV (PLWH) are affected by a higher incidence skin disorders, which are often associated with high morbidity and mortality. In particular, psoriasis affects PLWH severely and for a longer time than the general population. Human immunodeficiency virus (HIV) infection is characterized by a progressive decrease in CD4+ T-cell count, and it could seem paradoxical that psoriasis exacerbations are more frequent in this subset of patients than the general population, even though it is commonly observed at any stage of infection. For a long time, there have been limited therapeutic choices for PLWH affected by psoriasis. The introduction of the combined antiretroviral therapy dramatically changed the natural course of both HIV and psoriasis in PLWH, leading to an improvement of quality and duration of life. However, the clinical severity of psoriasis in PLWH often requires the use of immunosuppressant drugs. Knowledge about their safety and efficacy are limited to case-reports, small case-series and studies, therefore their use has not yet entered the routine. Further studies are needed to determine if immunosuppressive drugs can be safely and effectively used in PLWH affected by psoriasis and other autoimmune disorders.

A measles outbreak in Catania, Sicily: the importance of high vaccination coverage and early notification of cases for health and economic reasons.

Measles is a paediatric exanthematous disease. Even though vaccination has dramatically reduced measles morbidity and mortality, outbreaks still occur due to insufficient vaccination coverage and importation of the virus from endemic regions. Although child vaccination coverage in Italy has been broadened (from 74% in 2000 to 90.1% in 2011), outbreaks are still observed at a regional level. We describe epidemiological and clinical characteristics of cases reported from January 2009 to May 2010 to the Epidemiology Service of the Provincial Health Authority of Catania. We obtained demographic data and vaccination status from the database of the Epidemiology Service and clinical features and laboratory data from medical records. In all, 522 cases were notified: 286 males (54%), median age 12 years (interquartile range (IQR) 4-18); 401 cases (77%) were notified by the hospital, and 121 (23%) by general practitioners. Only one patient had been previously vaccinated. 52 cases were hospitalized, median age 18 years (IQR 17-23). We observed hypertransaminasaemia in 20 patients (38%), thrombocytopenia in 22 patients (42%) and a creatine phosphokinase increase in 16 (30%). Complications (pneumonia, haemorrhagic cystitis, acute hepatitis) occurred in 10 patients (19%), all older than 18. Recent outbreaks show that immunization practices are still insufficient. Most cases were recorded in adolescents and young adults; even if the vaccine has limited virus circulation in childhood, it did not prevent the infection of other age groups. The number of notifications also suggests that the phenomenon is underestimated. In order to monitor the disease we need early notification of cases and increased vaccination coverage.

A new sampling method for spleen stiffness measurement based on quantitative acoustic radiation force impulse elastography for noninvasive assessment of esophageal varices in newly diagnosed HCV-related cirrhosis.

In our study, we evaluated the feasibility of a new sampling method for splenic stiffness (SS) measurement by Quantitative Acoustic Radiation Force Impulse Elastography (Virtual Touch Tissue Quantification (VTTQ)).We measured SS in 54 patients with HCV-related cirrhosis of whom 28 with esophageal varices (EV), 27 with Chronic Hepatitis C (CHC) F1-F3, and 63 healthy controls. VTTQ-SS was significantly higher among cirrhotic patients with EV (3.37 m/s) in comparison with controls (2.19 m/s, P<0.001), CHC patients (2.37 m/s, P<0.001), and cirrhotic patients without EV (2.7 m/s, P<0.001). Moreover, VTTQ-SS was significantly higher among cirrhotic patients without EV in comparison with both controls (P<0.001) and CHC patients (P<0.01). The optimal VTTQ-SS cut-off value for predicting EV was 3.1 m/s (AUROC=0.96, sensitivity 96.4%, specificity 88.5%, positive predictive value 90%, negative predictive value 96%, positive likelihood ratio 8.36, and negative likelihood ratio 0.04). In conclusion, VTTQ-SS is a promising noninvasive and reliable diagnostic tool to screen cirrhotic patients for EV and reduce the need for upper gastrointestinal endoscopy. By using our cut-off value of 3.1 m/s, we would avoid endoscopy in around 45% of cirrhotic subjects, with significant time and cost savings.