Early Diagnosis and Linkage to Care: an Experience over 14 years of Point of Care Rapid HIV Testing.

Point-of-care rapid testing is one of the strategies to increase HIV screening. We present data on over 14 years of the "EASY Test Program", an ongoing cross-sectional collaborative project that provides free and anonymous rapid HIV testing in the metropolitan city of Milan, Italy. Overall, 22,186 HIV tests were performed, with a 0.52% prevalence of HIV infection; 100% of those diagnosed with HIV were linked to care. The "EASY Test Program" is an appropriate test-and-treat strategy, allowing a fast HIV assessment (24 hours). Motivated clinicians, in partnership with community associations, can perform an easy HIV screening out of hospitals in alternative settings, among individuals who in the majority of cases had never tested for HIV, ultimately providing an effective linkage to care.

Low-Wage Agricultural Migrant Workers in Apulian Ghettos, Italy: General Health Conditions Assessment and HIV Screening.

BACKGROUND: Approximately 500,000 migrants work in the agricultural sector in Italy. Many of them live in shantytowns, wrongly called "ghettos", far away from city centers, with no water, proper hygienic conditions or health services. The aim of this study is to assess general health conditions and HIV prevalence by giving hygienic and sanitary sustenance. METHODS: Between June 2019 and February 2020, we performed a screening campaign for HIV-diabetes-hypertension, involving migrants living in three Apulian establishments: ghetto Pista, "Sankara House" and "Arena House". RESULTS: Overall, 321 migrants were enrolled in the study. In the medical screening, one HIV test resulted positive. Hypertension was found in 12% of the migrants visited, diabetes in 2% and TB symptoms in 17%. Among others symptoms explored, muscle and joint pain/fatigue resulted in being the most frequent, and was reported by 34% of the migrants, followed by cough (10%). Significant predictors of muscle and joint pain/fatigue were: low BMI values (OR = 1.32; 95% CI 1.19-1.99), the absence of education (OR = 1.85; 95% CI 1.02-2.95), being employed with a regular contract (OR = 2.64; 95% CI 2.39-2.83) and living in the ghettos since >12 months (OR = 1.74; 95% CI 1.24-2.21). CONCLUSIONS: Our experience suggests that, in this population, the health condition is mainly linked to the specific working activities in the agricultural fields, as well as to the hygienic and living conditions, and that all of this is due to the lack of social protection in their life and job.

Effects of Pirfenidone and Nintedanib on Markers of Systemic Oxidative Stress and Inflammation in Patients with Idiopathic Pulmonary Fibrosis: A Preliminary Report.

INTRODUCTION: In vitro evidence suggests that pirfenidone and nintedanib, approved agents for the treatment of idiopathic pulmonary fibrosis (IPF), exert anti-inflammatory and anti-oxidant effects. We aimed to investigate such effects in vivo in IPF patients. METHODS: Systemic circulating markers of oxidative stress [nuclear factor erythroid 2-related factor 2 (Nrf2), thiobarbituric acid- reactive substances (TBARS), homocysteine (Hcy), cysteine (Cys), asymmetric dimethylarginine (ADMA) and ADMA/Arginine ratio, glutathione (GSH), plasma protein -SH (PSH), and taurine (Tau)] and inflammation [Kynurenine (Kyn), Tryptophan (Trp) and Kyn/Trp ratio] were measured at baseline and after 24-week treatment in 18 IPF patients (10 treated with pirfenidone and 8 with nintedanib) and in 18 age- and sex-matched healthy controls. RESULTS: Compared to controls, IPF patients had significantly lower concentrations of reduced blood GSH (457 ± 73 µmol/L vs 880 ± 212 µmol/L, p < 0.001) and plasma PSH (4.24 ± 0.95 µmol/g prot vs 5.28 ± 1.35 µmol/g prot, p = 0.012). Pirfenidone treatment significantly decreased the Kyn/Trp ratio (0.030 ± 0.011 baseline vs 0.025 ± 0.010 post-treatment, p = 0.048) whilst nintedanib treatment significantly increased blood GSH (486 ± 70 µmol/L vs 723 ± 194 µmol/L, p = 0.006) and reduced ADMA concentrations (0.501 ± 0.094 vs. 0.468 ± 0.071 µmol/L, p = 0.024). CONCLUSION: pirfenidone and nintedanib exert beneficial effects on specific markers of oxidative stress and inflammation in IPF patients.

Blood Cell Count Derived Inflammation Indexes in Patients with Idiopathic Pulmonary Fibrosis.

PURPOSE: Inflammation and immunity play a pivotal but yet unclear role in idiopathic pulmonary fibrosis (IPF), a chronic disorder characterized by progressive damage of lung parenchyma and severe loss of lung function despite optimal treatment. However, the pathophysiological and predictive role of combined blood cell count indexes of inflammation in IPF is uncertain. METHODS: Seventy-three patients with IPF and 62 healthy subjects matched for age, gender and smoking status were included in this cross-sectional study. RESULTS: We found significant differences in neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), monocyte to lymphocyte ratio (MLR), platelet to lymphocyte ratio (PLR), systemic inflammation response index (SIRI) and aggregate index of systemic inflammation (AISI) between IPF patients and healthy controls. In logistic regression, all combined blood inflammation indexes, barring PLR, were independently associated with the presence of IPF after adjusting for age, gender, body mass index and smoking status. Furthermore, significant associations between FVC% and NLR, LMR, SIRI and AISI, and between DLCO% and NLR, dNLR, LMR, SIRI and AISI, were observed. CONCLUSIONS: In conclusion, our data indicate significant alterations of combined blood cell count indexes of inflammation in IPF.

Clinical and spirometric variables are better predictors of COPD exacerbations than routine blood biomarkers.

BACKGROUND: Understanding the risk factors for exacerbations of COPD may help provide a more personalised approach to exacerbation prevention. METHOD: Observational, prospective, international, multicentre study aimed at identifying risk factors for exacerbations of COPD. Clinical variables, lung function and CAT scores were collected at baseline. In addition, routine blood biomarkers were also obtained, and patients were followed for 12 months. RESULTS: A total of 326 patients were included. Of these, 155 (47.5%) presented at least one exacerbation. The median time to the first exacerbation was 147 days. Exacerbators had more respiratory symptoms, more impairment in FEV1(%), FVC(%) and a worse CAT score. Regarding biomarkers, only C-reactive protein was significantly higher in exacerbators (2.8 (standard deviation (SD):3.8) mg/dL vs. 1.9 (SD:2.6) mg/dL; p = 0.037). In multivariate analysis, only CAT scores, FEV1(%) and previous exacerbations were significantly associated with having an exacerbation during follow-up. In the equation of risk, patients with a CAT score ≥15, FEV1(%) <55% and at least one exacerbation the previous year had a probability of 76% of having an exacerbation during the next year, compared with 17% in patients who had none of the previous variables. No biomarkers showed a significant association in multivariate analysis. CONCLUSIONS: Less than half of the patients presented an exacerbation during the one-year follow-up. CAT scores, FEV1(%) and previous exacerbations were the only variables associated with increased risk of exacerbations. Routine biomarkers did not provide additional information to evaluate the risk of exacerbations.

Association Between Routine Blood Biomarkers and Clinical Phenotypes and Exacerbations in Chronic Obstructive Pulmonary Disease.

Introduction: Chronic obstructive pulmonary disease (COPD) is associated with increased lung and systemic inflammation. We aimed to identify associations between easy-to-obtain blood biomarkers and the frequency and severity of exacerbations. Methods: Cross-sectional, multicentre study performed in four centres in Spain, Italy, Bulgaria, and Slovenia. Blood samples were obtained for blood cell count, C-reactive protein (CRP), alpha-1 antitrypsin (AAT) and fibrinogen analysis. The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and eosinophil/basophil ratio (EBR) were calculated. Firstly, patients were divided into clinical phenotypes according to the Spanish guidelines of COPD, and secondly, patients were classified into 2 groups: non-exacerbators (≤1 ambulatory exacerbation in the previous year) and exacerbators (≥2 ambulatory exacerbations or 1 hospitalisation in the previous year). A multivariate stepwise logistic regression model was performed to identify laboratory parameters associated with exacerbators. Results: A total of 355 patients with a mean age 66 years (SD=8.9) were included, and 64% were male. The mean FEV1% (forced expiratory volume in the first second) was 55% (SD=20%), and the mean COPD Assessment Test (CAT) score was 15.6 (SD=7.9). One hundred ninety-six (55.2%) patients were classified in the non-exacerbator group, and 159 (44.8%) were exacerbators. Patients in the exacerbators group presented lower haemoglobin levels (p=0.019) and ERB (p= 0.023) but higher CRP levels (p=0.001). In the multivariate analysis, females, higher levels of CRP, lower FEV1% and low EBR were independently related to exacerbators. Conclusion: Female sex, having a more severe impairment of lung function, higher CRP levels and a lower EBR are associated with an exacerbator phenotype in COPD.

HIV rapid test in a community setting as a strategy to improve access to HIV testing: data from a multicentre experience in Italy.

4,000 new HIV diagnoses and approximately 800 AIDS cases are still reported annually in Italy. Improving public awareness and bringing out HIV-undiagnosed individuals are keystones to progress towards the control of the HIV epidemic. For this purpose, the Open HIV TEST project was organized and delivered by the Italian NGO Anlaids, together with local infectious diseases specialists, in order to provide free access to HIV testing outside the healthcare setting. Between October 2017 and February 2019 six Open HIV TEST initiatives were delivered in six Italian cities (3 northern cities, 1 central and 2 southern cities). In all, 581 people were tested: the overall prevalence of HIV test reactivity was 0.7%. Participants were also asked about previous screenings and about their satisfaction with the initiative: previous HIV screening due to pregnancy or surgical procedures was reported mainly by participants in northern centres (p<0.001); finally, the initiative was considered useful and noteworthy by 99% of participants. Prevalence of HIV test reactivity in our experience was in line with national data. Our experience suggests that active testing and counselling strategies in community settings should be recommended and institutionalized by local health authorities in line with the 90-90-90 global strategy.

Dyspnoea, thoracic pain and fever in a young caucasian female: A case report.

INTRODUCTION: The diagnostic approach to patients with mediastinal pathology is not always simple and an improper diagnostic work-up can lead to significant diagnosis delay. PRESENTATION OF CASE: We report on the case of a young woman who was admitted to the Emergency Department complaining of thoracic pain, dyspnoea, fever and productive cough. The physical examination showed a painful swelling over the sternum's upper left margin, which had become evident 4 months earlier. A Computer Tomography showed the presence of a retrosternal oval lesion (5.5 x 4 cm) infiltrating the thoracic wall and showed the presence of discretely enlarged mediastinal lymph nodes in several mediastinal stations. DISCUSSION: The Multidisciplinary Team decided to perform an ultrasound-guided biopsy of the retrosternal mass that showed an inflammatory pattern, whereas microbiology tests proved negative. The lack of improvement with medical therapy (non steroideal anti-inflammatories and antibiotics) and the clinical suspicion of malignancy led us to perform a surgical biopsy of the mass that finally proved to be diagnostic for Hodgkin's lymphoma. CONCLUSIONS: Mediastinal masses with an aggressive behavior, should always be considered to be potentially malignant. Surgical biopsy, sometimes, can be the only way to correctly diagnose the pathological process, especially in the case of Hodgkin's lymphoma in which few diagnostic cells (Reed-Sternberg cells) are generally embedded in an abundant inflammatory background tissue.

Neutrophil to lymphocyte ratio and clinical outcomes in COPD: recent evidence and future perspectives.

Chronic obstructive pulmonary disease (COPD) is a disabling condition that is characterised by poorly reversible airflow limitation and inflammation. Acute exacerbations of COPD are a common cause of hospitalisation and death among COPD patients. Several biochemical markers have been studied as outcome predictors in COPD; however, their measurement often requires significant time and resources. Relatively simple biomarkers of inflammation calculated from routine complete blood count tests, such as the neutrophil to lymphocyte ratio (NLR), might also predict COPD progression and outcomes. This review discusses the available evidence from studies investigating the associations between the NLR, COPD exacerbations and death in this patient group.

Point-of-care testing for hepatitis C virus infection at alternative and high-risk sites: an Italian pilot study in a dental clinic.

The Infectious Diseases Department and the Department of Dentistry of San Raffaele Scientific Institute in Milan conducted a screening and prevention program, the "EASY HCV-test Program," at a dental clinic to increase the identification of unrecognized infections. Using a cross-sectional community-based study design, hygienists in the dental clinic offered patients a hepatitis C virus (HCV) rapid salivary test (OraQuick ADVANCE® Rapid HCV Antibody Test) with pre- and post-test counseling prior to initiation of their oral hygiene routine. From April 2015 to November 2015, the EASY HCV test was offered to 2650 patients visiting the Center of Oral Health and Prevention at the Department of Dentistry at San Raffaele Hospital in Milan. Among them, 2077 eligible volunteers were tested. The test showed positive reactivity in 22 cases; of these, 21 subjects were known to suffer from HCV, and the test confirmed their status. One subject was newly diagnosed with HCV infection. The results of this study suggest EASY HCV test screening conducted in dental clinics may constitute an effective strategy for increasing HCV testing among people at risk for infection.

Early diagnosis and retention in care of HIV-infected patients through rapid salivary testing: a test-and-treat fast track pilot study.

Aim of this study was to evaluate the efficacy and the retention-in-care of individuals diagnosed during six years of salivary HIV testing (EASY-test project). Among those linked-to-care at the Infectious Diseases Department of San Raffaele Hospital (Milan, Italy), the proportion of patients engaged, retained in care and virologically suppressed after the antiretroviral treatment was 96%, 100% and 95.2%, respectively. Results from our study suggest that salivary HIV testing may help bring to light cases of HIV infection otherwise undiagnosed, and thus favour a more rapid and wider reduction of the HIV infection burden at the population level.

Early diagnosis and retention in care of HIV-infected patients through rapid salivary testing: a test-and-treat fast track pilot study.

Aim of this study was to evaluate the efficacy and the retention-in-care of individuals diagnosed during six years of salivary HIV testing (EASY-test project). Among those linked-to-care at the Infectious Diseases Department of San Raffaele Hospital (Milan, Italy), the proportion of patients engaged, retained in care and virologically suppressed after the antiretroviral treatment was 96%, 100% and 95.2%, respectively. Results from our study suggest that salivary HIV testing may help bring to light cases of HIV infection otherwise undiagnosed, and thus favour a more rapid and wider reduction of the HIV infection burden at the population level.

Point-of-care testing for HCV infection: recent advances and implications for alternative screening.

Over the last few years, hepatitis C virus (HCV) infection has emerged as one of the most significant causes of chronic liver disease worldwide, with an estimated prevalence ranging from 2.2 to 3.0%. In Italy, approximately 2% of subjects are infected with HCV. Considering that acute HCV infection is usually asymptomatic, early diagnosis is rare. Those people who develop chronic infection, even though undiagnosed, may suffer serious liver damage, making chronic HCV infection a major health problem. New initiatives are needed to identify a submerged portion of patients with chronic viral hepatitis and to propose controls and antiviral treatments to avoid the progression to liver cirrhosis or hepatocellular carcinoma (HCC). Since January 2011, the Infectious Diseases Department of San Raffaele Scientific Institute in Milan has been carrying out a prevention program called "EASY test project", using a new oral test, the OraQuick® HCV rapid antibody test (OraSure technologies, Inc.). The main objective of the project is to evaluate the acceptability of an alternative, free and anonymous HCV test offer, available in different settings (Points of Care, STDs Prevention clinics and General Practitioner clinics). From January 2011 to April 2014, 29,600 subjects were approached to inform them about HCV infection and other sexually transmitted diseases; 4,507 (15.2% of the contacted subjects) of them, total eligible volunteers, performed HCV tests on saliva and completed the interview in the alternative POCTs. Twenty-seven subjects (0.6% of the total) turned HCV oral test reactive (27/4.507) during the evaluation period; all of them were confirmed by conventional test. All 27 patients were asymptomatic and without a history of HCV-re- lated symptoms. The results from this analysis suggest that the promotion of alternative HCV test screening has not yet been fully developed as a strategy to increase levels of HCV testing among people at risk for HCV infection. Increasing awareness of these alternative tests among individuals at risk and providers may be an appropriate strategy to increase the number of people who know their serological status. The recent introduction of rapid oral HCV antibody test could completely change the HCV diagnosis approach by facilitating the possibility of testing millions of people worldwide (in particular in the developing countries).

Expansion of CCR4+ activated T cells is associated with memory B cell reduction in DOCK8-deficient patients.

Hyper-IgE syndrome (HIES) is a genetic disorder characterized by elevated IgE serum levels, mostly due to mutations in STAT3 or DOCK8. Despite clinical heterogeneity between the two forms of the disease, clinical manifestations may not be conclusive for diagnosis and immunological differences are still unclear. Herein, we performed a detailed characterization of the T- and B-cell compartments by flow cytometry in seven HIES patients with homozygous DOCK8 mutations and six patients presenting heterozygous STAT3 mutations. We observed that DOCK8-deficient patients showed a marked reduction of naive and recent thymic emigrant (RTE) T lymphocytes together with a relative increase of activated T cells, most of which co-expressed the chemokine receptor CCR4, a marker of Th2 polarization. Moreover, an extreme reduction of memory B cells was detected, despite a normal/increased proportion of immunoglobulin-secreting cells. These observations indicate that DOCK8-deficient patients display a distinctive immunophenotype which is characteristic of this form of HIES.

[Impaired lung function and anemia from large hiatal hernia: a case report]. / Alterazioni della funzione respiratoria ed anemia da voluminosa ernia iatale: descrizione di un caso.

We present the clinical case of a 54 years old man who accessed for dyspnea and severe anemia. After being transfused, he underwent to gastroscopy, which showed an erosive gastritis with large hiatal hernia. The hernia was surgically reduced with laparoscopic hiatoplastic and Nissen-Rossetti fundoplication. In conclusion, dyspnea is not merely a medical competence but also a surgical one.

Cross-sectional study of community serostatus to highlight undiagnosed HIV infections with oral fluid HIV-1/2 rapid test in non-conventional settings.

The submerged portion of undiagnosed HIV infection in Italy is about 30% of subjects found seropositive. This fact represents one of the most important public health problems hindering the control of infection progression. This means we need to fight unawareness and social stigma and promote easy and friendly access to HIV test. We developed a Prevention Program called "EASY test Project", offering a new rapid HIV test on oral fluid, to evaluate the acceptability of an alternative, free and anonymous test available in different settings (on board a "Motor Home" at public events, Points of Care, STDs outpatient prevention units and GP surgeries). From December 2008 to December 2012 we performed 7,865 HIV saliva tests, with 50 new infections found (0.6% of the total) out of 140,000 informed subjects. From the self-reported characteristics of respondents, the population approaching the EAST test project was represented by males (70%) aged between 20 and 50 years, 61% with a medium-high education level, 62% homosexuals (MSM), 88% reported unsafe sexual behaviours, and 48% had never undergone an HIV screening test. In five years of the Prevention Program, 100% of subjects interviewed gave a general favorable consent in approaching rapid and not invasive screening, immediate return of the result, and a timely specialized approach and treatment of HIV positive subjects. Results from our study confirm that the rapid and alternative test may contribute to HIV prevention strategies and to the control of the spread of infection and HIV disease progression by reaching a larger population, particularly when and where regular screening procedures are difficult to obtain or are not preferred.

An unusual case of stent migration after celiac trunk endovascular revascularization.

A 61-year-old woman underwent celiac trunk stenting to treat abdominal angina. Three months later, she was readmitted for recurrent symptoms. Computed tomography control revealed the migration of the stent into the splenic artery. No sign of vessel injury or end-organ ischemia was detected. Repeat stenting of the celiac trunk was performed; the postoperative course was uneventful. 12 months later, the patient was asymptomatic with the second stent in its correct position, and she was asymptomatic for mesenteric ischemia.

Central nervous system involvement at first relapse in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy without intrathecal prophylaxis.

BACKGROUND: The prevalence of and risk factors for central nervous system recurrence in patients with acute promyelocytic leukemia are not well established and remain a controversial matter. DESIGN AND METHODS: Between 1996 and 2005, 739 patients with newly diagnosed acute promyelocytic leukemia enrolled in two consecutive trials (PETHEMA LPA96 and LPA99) received induction therapy with all-trans retinoic acid and idarubicin. Consolidation therapy comprised three courses of anthracycline monochemotherapy (LPA96), with all-trans retinoic acid and reinforced doses of idarubicin in patients with an intermediate or high risk of relapse (LPA99). Central nervous system prophylaxis was not given. RESULTS: Central nervous system relapse was documented in 11 patients. The 5-year cumulative incidence of central nervous system relapse was 1.7% (LPA96 3.2% and LPA99 1.2%; p=0.09). The cumulative incidence was 0%, 0.8%, and 5.5% in low-, intermediate-, and high-risk patients, respectively. Relapse risk score (p=0.0001) and the occurrence of central nervous system hemorrhage during induction (5-year cumulative incidence 18.7%, p=0.006) were independent risk factors for central nervous system relapse. CONCLUSIONS: This study shows a low incidence of central nervous system relapse in patients with acute promyelocytic leukemia following therapy with all-trans retinoic acid and anthracycline without specific central nervous system prophylaxis. Central nervous system relapse was significantly associated with high white blood cell counts and prior central nervous system hemorrhage, which emerged as independent prognostic factors.

Differentiation syndrome in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline chemotherapy: characteristics, outcome, and prognostic factors.

Differentiation syndrome (DS) can be a life-threatening complication in patients with acute promyelocytic leukemia (APL) undergoing induction therapy with all-trans retinoic acid (ATRA). Detailed knowledge about DS has remained limited. We present an analysis of the incidence, characteristics, prognostic factors, and outcome of 739 APL patients treated with ATRA plus idarubicin in 2 consecutive trials (Programa Español de Tratamientos en Hematología [PETHEMA] LPA96 and LPA99). Overall, 183 patients (24.8%) experienced DS, 93 with a severe form (12.6%) and 90 with a moderate form (12.2%). Severe but not moderate DS was associated with an increase in mortality. A bimodal incidence of DS was observed, with peaks occurring in the first and third weeks after the start of ATRA therapy. A multivariate analysis indicated that a WBC count greater than 5 x 10(9)/L and an abnormal serum creatinine level correlated with an increased risk of developing severe DS. Patients receiving systematic prednisone prophylaxis (LPA99 trial) in contrast to those receiving selective prophylaxis with dexamethasone (LPA96 trial) had a lower incidence of severe DS. Patients developing severe DS showed a reduced 7-year relapse-free survival in the LPA96 trial (60% vs 85%, P = .003), but this difference was not apparent in the LPA99 trial (86% vs 88%).

Risk-adapted treatment of acute promyelocytic leukemia with all-trans retinoic acid and anthracycline monochemotherapy: long-term outcome of the LPA 99 multicenter study by the PETHEMA Group.

A previous report of the Programa de Estudio y Tratamiento de las Hemopatías Malignas (PETHEMA) Group showed that a risk-adapted strategy combining all-trans retinoic acid (ATRA) and anthracycline monochemotherapy for induction and consolidation in newly diagnosed acute promyelocytic leukemia results in an improved outcome. Here we analyze treatment outcome of an enlarged series of patients who have been followed up for a median of 65 months. From November 1999 through July 2005 (LPA99 trial), 560 patients received induction therapy with ATRA plus idarubicin. Patients achieving complete remission received 3 courses of consolidation followed by maintenance with ATRA and low-dose chemotherapy. The 5-year cumulative incidence of relapse and disease-free survival were 11% and 84%, respectively. These results compare favorably with those obtained in the previous LPA96 study (P = .019 and P = .04, respectively). This updated analysis confirms the high antileukemic efficacy, low toxicity, and high degree of compliance of a risk-adapted strategy combining ATRA and anthracycline monochemotherapy for consolidation therapy.