A high rate of HIV-1 acquisition post immigration among migrants in Sweden determined by a CD4 T-cell decline trajectory model.

OBJECTIVES: There is a lack of knowledge about the extent to which migrants become HIV-1 infected after arrival in European countries. The objective of this study was to assess the extent to which migrants to Sweden become HIV-1 infected post immigration using a CD4 T-cell decline trajectory model. METHODS: All migrants (n = 2268) who were ≥ 15 years old, were diagnosed with HIV-1 infection in the period 1983-2013, had a known year of arrival in Sweden, did not have primary HIV infection and were not infected via mother-to-child transmission were included in the study. The CD4 T-cell decline trajectory model was applied and estimates of HIV acquisition were compared to the clinical reports. Phylogenetic analysis was performed in a subset of patients to explore whether this would favour the model or the doctor's estimate. RESULTS: The model estimated 19% of individuals to have been infected after arrival in Sweden, whereas the physician's estimate was 12%. In 79% of cases the estimates agreed. Discordance was predominantly seen when the doctor estimated HIV acquisition to have occurred before arrival in Sweden, while the model estimated it to have occurred after arrival in Sweden, and this type of discordance was seen in 10% of all patients. The probability of a discordance was greater for older patients, those with a high first CD4 T-cell count and those infected via heterosexual transmission. The phylogenetic analysis showed a higher concordance with the CD4 model than with the clinical reports (36 vs. 13%, respectively). CONCLUSIONS: The model indicated that a substantially higher proportion of migrants are infected after arrival in Sweden than estimated using clinical routine reports. It is therefore important to further emphasize primary preventive measures among migrants who have established themselves in their new country.

Assessing cervical intraepithelial neoplasia as an indicator disease for HIV in a low endemic setting: a population-based register study.

OBJECTIVES: To analyse whether the prevalence of undiagnosed HIV among (1) all women in Sweden and (2) migrant women, diagnosed with cervical intraepithelial neoplasia grade 2 or worse CIN2+ reaches the threshold of 0.1%, which has been suggested to be cost-effective for HIV testing. DESIGN: Population-based register study. SETTING: Counties of Stockholm and Gothenburg, Sweden, 1990-2014. POPULATION: All women, born between 1940 and 1990, with at least one cervical cytology or histology registered in the Swedish National Cervical Screening Register (NKCx). METHODS: Data were collected from the NKCx and the Swedish National HIV register. The proportion of women with undiagnosed HIV among women with CIN2+ compared with women with a normal/mildly abnormal cytology/histology was assessed. MAIN OUTCOME MEASURES: Proportion of women with undiagnosed HIV. RESULTS: The proportion of undiagnosed HIV was higher among all women with CIN2+ than among those without CIN2+ : 0.06% (95% CI 0.04-0.08) versus 0.04% (95% CI 0.04-0.04); P = 0.017). Among migrant women, the proportion of undiagnosed HIV was higher among those with CIN2+ than among those without [0.30% (95% CI 0.20-0.43) versus 0.08% (95% CI 0.07-0.10); P < 0.001] and exceeded 0.1%, suggesting the cost-effectiveness of HIV testing. Women with undiagnosed HIV at the time of CIN2+ had a significantly lower nadir CD4+ T-cell count, as a measure of immunosuppression, compared with women without CIN2+ before HIV diagnosis (median nadir CD4, 95 cells/mm3 versus 210 cells/mm3 ; P < 0.01). CONCLUSIONS: HIV testing should be performed in migrant women with unknown HIV status diagnosed with CIN2+ . TWEETABLE ABSTRACT: HIV testing should be performed in migrant women with unknown HIV status diagnosed with CIN2+ .

Deficiencies in the health care system contribute to a high rate of late HIV diagnosis in Sweden.

OBJECTIVES: The aim of the study was to identify factors in HIV-infected patients and the health care system which contribute to late diagnosis. METHODS: All patients who were newly diagnosed with HIV infection at 12 clinics in Sweden over a period of 2.5 years (n = 575) were included in the study, corresponding to three-quarters of newly diagnosed HIV infections in the country. The patients were classified as non-late presenters or late presenters (LPs), defined as those with a CD4 count < 350 cells/µL or AIDS. LPs were subdivided into those without and those with advanced HIV disease, which was defined as a CD4 count < 200 cells/µL or AIDS. Demographics, missed AIDS and HIV-associated symptoms in the preceding 3 years, immigration date, and health examination at immigration were recorded. RESULTS: Fifty-eight per cent of the patients were LPs, of whom 66% had advanced disease. Age > 30 years, origin in sub-Saharan Africa or Eastern Europe/Asia/the Pacific region, and country of transmission being in sub-Saharan Africa or unknown were associated with late presentation. Half of the patients of non-Swedish origin had lived for more than 1 year in Sweden at diagnosis and 66% had a missed HIV testing opportunity at immigration. Twenty-seven per cent of all patients had presented for health care with AIDS- and/or HIV-associated conditions without having an HIV test. Sixteen per cent had a history of symptoms without seeking care. CONCLUSIONS: Deficiencies in the health care system with missed HIV testing opportunities contribute to the high proportion of late presenters in Sweden, especially among migrants. With increased testing at immigration and further incorporation of "indicator-guided" testing in general practice, most patients could be diagnosed earlier.

The possible role of glutathione-S-transferase activity in diabetic nephropathy.

The most common cause of end stage renal disease is diabetic nephropathy. An early diagnosis may allow an intervention to slow down disease progression. Recently, it has been hypothesized that glutathione-S-transferase (GST) activity may be a marker of severity of chronic kidney disease. In particular, a lower GST activity is present in healthy subjects compared to patients with nephropathy. In the present review we illustrate the scientific evidence underlying the possible role of GST activity in the development of diabetic nephropathy and we analyze its usefulness as a possible early biomarker of this diabetic complication.

IN VITRO ANALYSIS OF MARGINAL ADAPTATION AND RESISTANCE OF DIFFERENT DENTAL COMPOSITES: STEREO AND SCANNING ELECTRON MICROSCOPIC EVALUATION.

To compare the performance, by scanning electron microscopic analysis, of the interface between tooth and four commercial restorative composite resins in Class I cavities following exposure to acidified artificial solution, pH 4.5, with a background electrolyte composition similar to saliva, 600 teeth were divided into 4 groups. The first group was treated with microfilled light-cured Heliomolar; the second group with Durafill; the third group with the microfilled self-cured Isomolar; and the fourth group was treated using the hybrid self-cured Miradapt. All teeth of each group were randomly divided into two sub-groups: A) a control group that was immersed in artificial saliva (pH 7); B) a study group that was immersed in artificial saliva acidified with phosphoric acid (pH 4.5) in order to obtain artificial caries. The samples were examined by scanning electron microscopy. Data were analyzed using Pearson’s Chi-squared test (χ2) with R statistical software. The statistical analyses demonstrated significant differences in the two sub-groups A and B when considered for the light-cured composites whereas no difference was monitored for self-cured composites. Statistical analysis (p minore di 0.001) also demonstrated that the type of composite strongly influenced the infiltration grade. Our results demonstrate that incremental layering techniques might improve the marginal adaptation for light-cured composites, while self-cured show a marked polymerization contraction which can cause marginal breakdown.

The possible role of physical activity in the modulation of gut microbiota in chronic kidney disease and its impact on cardiovascular risk: a narrative review.

Chronic degenerative non-communicable diseases (CDNCDs), in particular chronic kidney disease, induce gut microbiota (GM) dysbiosis, which, in turn, worsens the progression of CDNCDs and patients' quality of life. We analyzed literature studies to discuss the possible positive and beneficial impact of physical activity on GM composition and CV risk in CKD patients. Regular physical activity seems to be able to positively modulate the GM, reducing the systemic inflammation and consequently the production of uremic gut-derived toxins, which are directly correlated with the increase of cardiovascular risk. In particular, the accumulation of indoxyl sulphate (IS) seems to be able to induce vascular calcifications, vascular stiffness and cardiac calcifications, while p-Cresyl sulphate (p-CS) seems to be able to exert a cardiotoxic action through metabolic pathways, capable of inducing oxidative stress. In addition, trimethylamine N-oxide (TMAO) can alter lipid metabolism, inducing the production of foam cells and causing an accelerated atherosclerosis process. In this context, a regular physical activity program seems to represent an adjuvant non-pharmacological approach to the clinical management of CKD patients.

Screening of Fabry Disease of patients in renal replacement therapy in a population from Lazio (Italy).

OBJECTIVE: Fabry's disease (FD) is a genetic disorder of lysosomal storage characterized by the intralysosomal accumulation of globotriaosylceramide (Gb3). This genetic mutation causes a total or partial deficit of the α-galactosidase (GAL) enzyme activity. FD has an incidence of 1:40000-60000 born alive. Its prevalence is higher in specific pathological conditions like chronic kidney disease (CKD). The aim of this study was to evaluate the FD prevalence in Italian renal replacement therapy (RRT) patients from Lazio region. PATIENTS AND METHODS: 485 patients in RRT (hemodialysis, peritoneal dialysis, and kidney transplantation) were recruited. The screening test was performed on venous blood sample. The latter was analyzed using specific FD diagnostic kit, based on the analysis of dried blood spots on filter paper. RESULTS: We found 3 cases of positivity to FD (1 female and 2 males). In addition, 1 male patient was identified with biochemical alteration indicative of GAL enzyme deficiency with a genetic variant of the GLA gene of unknown clinical significance. The FD prevalence in our population was 0.60% (1 case out 163), it rises to 0.80% (1 case out of 122) if the genetic variant of unknown clinical significance is considered. Comparing the three subpopulations, we observed a statistically significant difference in GAL activity in transplanted patients compared to dialysis patients (p<0.001). CONCLUSIONS: Considering the presence of an enzyme replacement therapy able to modify FD clinical history, it is essential to try to implement FD early diagnoses. However, the screening is too expensive to be extended on large scale, due to the low prevalence of the pathology. The screening should be performed on high-risk populations.

Correlation between physical activity, nutritional intake, and osteoporosis in postmenopausal women: a preliminary evaluation.

OBJECTIVE: Osteoporosis is a chronic metabolic syndrome associated with debilitating consequences that represents one of the major non-communicable diseases and the most common bone illness that affects both men and women. This observational study evaluates the amount of physical activity and the nutritional intake in a group of postmenopausal women who have a sedentary job. PATIENTS AND METHODS: All subjects underwent a medical evaluation, a body impedance analysis to evaluate body composition (fat mass, fat-free mass, and body cell mass), and a dual-energy X-ray absorptiometry to analyze bone mineral density. Additionally, a 3-day food record questionnaire and the International Physical Activity Questionnaire were administered respectively to evaluate patients' foods and beverages assumptions and the participants' Physical Activity levels. RESULTS: The study showed that most of the patients had a moderate activity level and inadequate calcium and vitamin D assumption compared to guidelines. CONCLUSIONS: The onset of osteoporosis seemed to be reduced at higher levels of leisure time, domestic, and transport activities, even in subjects who have a sedentary job and insufficient assumption of micronutrients.

Link between gut microbiota dysbiosis and chronic kidney disease.

During chronic kidney disease (CKD), typical alterations in the gut microbiota are observed. The kidney no longer plays the role of the main excretory organ as this function is performed by the intestine. In CKD patients, an alteration of intestinal permeability and a degradation of the protective mucous layer are observed. These changes in the intestinal barrier allow the passage of bacterial material from the intestine to the bloodstream through the intestinal wall. This phenomenon contributes to the induction of the chronic inflammatory state, typical of CKD. In nephropathic patients, there is an increase in circulation of p-cresyl sulfate (p-CS), indoxyl sulphate (IS), indole-3 acetic acid (IAA) and trimethylamine-N-oxide (TMAO), all gut-derived uremic toxins. The changes in gut microbiota composition are related to CKD stage and this phenomenon is exacerbated in hemodialysis (HD) adult and pediatric patients. Interestingly, it is observed a positive shift in gut microbiota composition after renal transplantation and at the same time a reduction of circulating gut-derived uremic toxins. Either gut dysbiosis or uremic toxins accumulation contribute to the CKD onset and progression.

Severe giant cell arteritis associated with essential thrombocythaemia.

Giant-cell arteritis (GCA) is a chronic vasculitis of the elderly usually involving the ophthalmic arteries, which can result in visual loss. High platelet counts may have some pathogenic significance in the obstruction of the ophthalmic circulation and a few cases of associated essential thrombocythaemia and GCA have been described. Here we report a case of severe temporal arteritis associated with essential thrombocythaemia.

Transarterial chemoembolization (TACE) for unresectable HCC: a new life begins?

BACKGROUND AND OBJECTIVES: To provide an overview on the loco-regional therapy performed by transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC), either as sole, either as neoadjuvant to surgery or bridge therapy to orthotopic liver transplantation (OLT). EVIDENCE AND INFORMATION SOURCES: The current review is based on an analysis of the current literature and the caseload experience of the Authors on this topic. STATE OF THE ART: Chemoembolization combines de-arterialization of the tumor and selective delivery of chemotherapeutic agents into tumor's feeding vessels during angiography. Tumor ischemia raises the drug concentration compared to infusion alone and extends the retention of the chemotherapeutic drug. As locoregional therapy, TACE allows a complete local tumor control of 25-35% and permits an increase of survival in patients with intermediate HCC according to Barcelona-Clinic Liver Cancer (BCLC) classification. Excellent results were also achieved by combined therapies, such as with percutaneous ethanol injection or radiofrequency ablation, as neoadjuvant therapy prior to liver resection and in some circumstances as a bridging tool before liver transplantation. PERSPECTIVES: Drug eluting beads are microspheres that can be loaded with doxorubicin and induce toxic and ischemic necrosis with the same device; that allows an increase of drug selectively exposed to tumor cells and simultaneously a reduction of systemic toxicity. Tumor embolization induces a neoangiogenic reaction with a significant growth of adiacent satellites, so the association with sorafenib has a strong rationale for a combined therapy and is currently under investigation. CONCLUSIONS: Today TACE is the standard of care for treatment of intermediate hepatocellular carcinoma. To get the best performance it should be tailored according to the individual patient's condition.

Mediterranean diet and the prevention of non-alcoholic fatty liver disease: results from a case-control study.

OBJECTIVE: Few studies report that Mediterranean dietary (MD) pattern has a beneficial role in the progression of non-alcoholic fatty liver disease (NAFLD). Evidence on its potential effect on the onset of disease are, however, scanty. With our study, we evaluated whether MD affects the risk of NAFLD with a large case-control study performed in Italy. PATIENTS AND METHODS: Three hundred and seventy-one cases of NAFLD and 444 controls were questioned on the demographic data and their dietary habits before diagnosis. Additionally, information about lifestyles and other related diseases, such as hypertension and diabetes mellitus were collected. The MD adherence was assessed using a pre-defined Mediterranean Diet Score (MDS). Odds ratios (OR) and 95% confidence intervals (CI) were obtained using a multiple logistic regression model. RESULTS: A high adherence to the MD is significantly associated with decreased risk of NAFLD (OR: 0.83 95% CI: 0.71-0.98). When the different MD components were examined separately, higher legumes consumption (OR: 0.62 95% CI: 0.38-0.99) and high fish consumption (OR 0.38 95% CI: 0.17-0.85) were reported to be protective against NAFLD. CONCLUSIONS: Our study shows that a high adherence to the MD decreases the risk of NAFLD.

The diagnostic performance of PIVKA-II in metabolic and viral hepatocellular carcinoma: a pilot study.

OBJECTIVE: Hepatocellular carcinoma (HCC) is a primary liver tumor derived from metabolic or viral chronic hepatitis, with few treatment options in advanced cases. New biomarkers that allow improving diagnosis and staging are widely desired. Here, we aim to evaluate the performance of Protein Induced by Vitamin K Absence or Antagonist-II (PIVKA-II) in combination with α-fetoprotein (AFP), in the diagnosis of HCC in patients with metabolic or viral hepatitis. PATIENTS AND METHODS: We enrolled 60 HCC patients (20 metabolic and 40 viral) and 20 healthy subjects (HS) as negative controls. PIVKA-II, AFP, Matrix metalloproteinase-9 (MMP-9) and Fibroblast growth factor (FGF) serum levels were assessed by immunoassays. RESULTS: AFP and PIVKA-II levels were obviously higher in patients than in HS. AFP displayed a better diagnostic performance than PIVKA-II for viral HCC while PIVKA-II was better for metabolic HCC. The combination of the two biomarkers did not improve the discriminating ability. CONCLUSIONS: PIVKA-II may be considered an independent predictor of macrovascular invasion from HCC cells and it can be used to better stratify HCC patients and should be evaluated in prospective studies for early detection of advanced HCC in metabolic subjects.

Acute HEV hepatitis: clinical and laboratory diagnosis.

OBJECTIVE: Hepatitis E Virus (HEV) is probably the most common cause of acute hepatitis worldwide. It has been regarded for a long time as a disease limited to developing countries. Recently, the refinement of diagnostic techniques, on the one hand, and migratory flows, on the other hand, have also led to the identification of an increased number of HEV infections in industrialized countries. Four HEV genotypes have been identified across the world, with different epidemiological burdens and a wide range of clinical presentations. Here, we report a case series of acute HEV hepatitis observed in the last three years in our hospital. PATIENTS AND METHODS: We performed a search for HEV IgM and IgG in all subjects admitted for acute hepatitis without evidence of other possible infectious, toxic or metabolic causes of liver damage. In subjects with HEV IgM positivity, the search for HEV-RNA was performed. RESULTS: We diagnosed eight acute HEV infections: 2 epidemic and 6 sporadic forms. HEV-RNA was detected in serum in 2 cases. CONCLUSIONS: HEV infection appears to be a cause of acute hepatitis that we must keep in mind even in developed countries.

Critical analysis of major and ancillary features of LI-RADS v2018 in the differentiation of small (≤ 2 cm) hepatocellular carcinoma from dysplastic nodules with gadobenate dimeglumine-enhanced magnetic resonance imaging.

OBJECTIVE: To evaluate the performance of major features, ancillary features, and categories of Liver Imaging Reporting and Data System (LI-RADS) version 2018 at magnetic resonance (MR) imaging in the differentiation of small hepatocellular carcinoma (HCC) from dysplastic nodules (DNs). PATIENTS AND METHODS: This retrospective study included cirrhotic patients with pathologically proven untreated HCCs and DNs (≤ 2 cm) and liver MR imaging performed with gadobenate dimeglumine contrast agent within 3 months before pathological analysis, between 2015 and 2018. 37 patients with 43 observations (17 HCCs and 26 DNs) met the inclusion criteria. Two radiologists assessed major and ancillary imaging features for each liver observation and assigned a LI-RADS v2018 category in consensus. Estimates of diagnostic performance of major features, ancillary features, and LI-RADS categories were assessed based on their sensitivity, specificity, positive (PPV), and negative predictive values (NPV). RESULTS: Major features (nonrim arterial phase hyperenhancement, nonperipheral "washout", and enhancing "capsule") had a sensitivity of 94.1%, 88.2%, and 41.2%, and a specificity of 57.7%, 42.3%, and 88.5% for HCC, respectively. Ancillary features (hepatobiliary phase hypointensity, mild-moderate T2 hyperintensity, restricted diffusion, and fat in the lesion more than adjacent liver) had a sensitivity of 94.1%, 64.7%, 58.8%, and 11.8%, and a specificity of 26.9%, 61.5%, 65.4%, and 76.9% for HCC, respectively. The LR-5 category (determined by using major features only vs. the combination of major and ancillary features) had a sensitivity of 88.2% at both evaluations and a specificity of 76.9% and 80.8% for HCC, respectively. The combination of LR-4, LR-5 categories (determined by using major features only vs. the combination of major and ancillary features) had a sensitivity of 94.1% at both interpretations and a specificity of 65.4% and 26.9% for HCC, respectively. The use of ancillary features modified LI-RADS category in 25.6% of observations (11/43), predominantly upgraded from LR-3 to LR4 (10/11), increasing the proportion of low-grade DNs and high-grade DNs categorized as LR-4 (from 15.4% to 61.5% and from 7.7% to 46.1%, respectively). CONCLUSIONS: The added value of ancillary features in combination with major features is limited for the non-invasive diagnosis of small HCC; however, their use modifies the final category in a substantial proportion of observations from LR-3 to LR-4, thus allowing possible changes in the management of patients at risk for HCC.

[Radon exposition preliminary research in a Sicilian territory]. / Esposizione a radon indagine preliminare su un territorio siciliano.

Radon toxicity on human body is well known from along (in 1988 radon has been classified as first type carcinogen, after only to tobacco's smoke, as cause of lung's cancer). Based on known scientific data, preliminary study has been conducted by the AA. It concerns radon exposition on inhabitants living in a Sicilian territory featured by previous seismic events: the territory and the town of Montevago. The project has been sponsored by ARPA Palermo. The territory of Montevago has been divided in several areas in order to assign detectors homogeneously, to begin the environmental sampling. In the period between May and October 2006, instruments has been calibrated and standardization of the procedure has been completed, in collaboration with Centro Studi Nucleare Enrico Fermi del Dipartimento di Ingegneria Nucleare del Politecnico di Milano. The values obtained result in European range.

Fatty liver and drugs: the two sides of the same coin.

Drug-induced liver injury (DILI) is a common and underestimated cause of liver disease. Several drugs and other xenobiotics can be the cause of different clinicopathologic patterns of liver disease. Steatosis and steatohepatitis are rare but well-documented types of DILI. Over the past decades commonly used drugs like amiodarone, tamoxifen, irinotecan, methotrexate, valproic acid and glucocorticoids have been recognized to be associated with steatosis. Even though the pathophysiological pathways are still only partially understood, inhibition of mitochondrial beta-oxidation, reduced very low-density lipoprotein secretion, insulin resistance induction and increased de novo synthesis or increased liver uptake of fatty acids are considered the main pathogenic mechanisms through which drugs can lead to hepatic steatosis. On the other hand, fatty liver itself is a very common clinical condition, and there is a growing awareness of the potential risk factors for DILI due to the underlying metabolic condition itself.