Hepatitis C virus and non-Hodgkin's lymphomas:Metaanalysisof epidemiology data and therapy options

Hepatitis C virus(HCV) is a global health problem affecting a large fraction of the world's population: This virus is able to determine both hepatic and extrahepatic diseases. Mixed cryoglobulinemia, a B-cell "benign" lymphoproliferative disorders, represents the most closely related as well as the most investigated HCVrelated extrahepatic disorder. Since this virus is able to determine extrahepatic [non-Hodgkin's lymphoma(NHL)] as well as hepatic malignancies(hepatocellular carcinoma), HCV has been included among human cancer viruses. The most common histological types of HCV-associated NHL are the marginal zone, the lymphoplasmacytic and diffuse large cell lymphomas. The role of the HCV in the pathogenesis of the B-cell lymphoproliferative disorders is confirmed also by the responsiveness of the NHL to antiviral therapy. The purpose of this review is to provide an overview of the recent literature and a meta analysis of the epidemiology data, to explain the role of HCV in the development of NHL's lymphoma. Furthermore, the possibility to treat these HCV-related NHL with the antiviral therapy or with other therapeutic options, like chemotherapy, is also discussed.

Ventricular Arrhythmia in the Fontan Circulation:Prevalence,Risk Factors and Clinical Implications

Objective:Sudden cardiac death(SCD)and malignant ventricular arrhythmia(VA)are increasingly recognized as important issues for people living with a Fontan circulation,but data are lacking.We sought to characterize the cohort who had sudden cardiac death,most likely related to VA and/or documented VA in the Australia and New Zealand Fontan Registry including risk factors and clinical outcomes.Methods:A retrospective cohort study was performed.Inclusion criteria were documented non-sustained ventricular tachycardia,sustained ventricular tachycardia,ventricular fibrillation,resuscitated cardiac arrest or SCD>30 days post-Fontan completion.Results:Of 1611 patients,20(1.2%)had VA;14(1.0%)had VA without SCD and 6(<1%)had SCD(6%of all deaths recorded in Registry;5 of those had documented VA at the time of arrest and 1 was presumed to be VA-associated).The median age at first VA was 20.5(14–32)years,10(50%)were females,and the median age at Fontan operation was 8(4–17)years.On univariable analysis,hypoplastic left heart syndrome(p=0.03)and older age Fontan operation(p<0.001)were associated with VA.Earlier Fontan era(p<0.003),atriopulmonary Fontan(p<0.001),pre-Fontan atrioventricular valve repair(p=0.013)pre-or post-Fontan atrial arrhythmia(p=0.010)were associated with SCD.Patients with VA had a 3 times higher risk of death or heart transplant(HR 3.27(1.19,8.98),p=0.02).Conclusions:A proportion of people living with a Fontan circulation have malignant VA.Routine VA screening in this cohort is essential.More data are needed to aid risk stratification.

Pre-illness changes in dietary habits and diet as a risk factor for inflammatory bowel disease: A case-control study

AIM: To evaluate whether symptoms of inflammatory bowel disease (IBD), before diagnosis modify dietary habits, and to investigate the pre-illness diet in patients with recent IBD in comparison with an age-matched healthy control group. METHODS: Overall, 83 new cases of IBD (41 ulcerative colitis, 42 Crohn's disease) and 160 healthy controls were studied. Portions per week of 34 foods and beverages before onset of symptoms were recorded using a validated questionnaire. Duration of symptoms before IBD diagnosis, presence of specific symptoms and their impact on subjective changes in usual dietary habits were also recorded. The association between diet and IBD was investigated by multiple logistic regression and dietary patterns were assessed by factor analysis. RESULTS: Changes in dietary habits, due to the presence of symptoms, were reported by 38.6% of patients and were not significantly related to specific symptoms, rather to long duration of symptoms, only in Crohn's disease patients. In IBD patients who did not change dietary habits, moderate and high consumption of margarine (OR = 11.8 and OR = 21.37) was associated with ulcerative colitis, whilst high consumption of red meat (OR = 7.8) and high intake of cheese were associated with Crohn's disease. CONCLUSION: More than one third of IBD patients change dietary habits before diagnosis. Margarine, red meat and cheese increase the risk of ulcerative colitis and Crohn's disease.

Association between the levels of prostaglandin E2 in tears and severity of dry eye

AIM: To investigate the relationship between the levels of prostaglandin E2(PGE2) in tears and dry eye disease severity based on both clinical symptoms and signs.METHODS: Tear samples were collected from 36 non-Sj?gren syndrome dry eye patients(10 males and 26 females, mean age 50.11±11.17 y). All participants completed the Ocular Surface Disease Index(OSDI) questionnaire and underwent a detailed ophthalmic examination including, tear film breakup time(TBUT), ocular surface fluorescein staining, Schirmer I test, and meibomian gland assessment. The level of PGE2 in tears was measured using enzyme-linked immunosorbent assay(ELISA). The independent associations between tear PGE2 levels and other variables including demographics, OSDI scores, TBUT, Schirmer scores, ocular surface staining scores, and stage of meibomian gland dysfunction(MGD) were evaluated using linear regression analysis. RESULTS: The mean PGE2 level in tears of dry eye patients was 537.85±234.02 pg/mL. The tear PGE2 levels significantly positively correlated with OSDI scores(R=0.608, P<0.001), however, they did not significantly associate with TBUT(R=0.153, P=0.373), Schirmer scores(R=-0.098, P=0.570), ocular surface staining scores(R=0.282, P=0.095), and stage of MGD(R=-0.107, P=0.535).Male sex was significantly negatively correlated with tear PGE2 levels.CONCLUSION: The levels of PGE2 in tears are positively correlated with dry eye symptoms. However, no significant association was found between tear PGE2 levels and the results of other common dry eye diagnostic tests.

Acute Syphilitic Hepatitis in the Early Secondary Phase: A Case Report and Literature Review

Background: The incidence of syphilis is clearly increasing. It is a source of visceral damage, particularly in the secondary phase. Acute syphilitic hepatitis is a rare clinical entity classically described but under-diagnosed because of its non-specific presentation. Case Presentation: We report the case of a 25-year-old French woman, without comorbidity, sexually active, having unprotected sex with only one partner. She was admitted to our unit for jaundice and a disturbed liver function test preceded 3 weeks earlier by a rash. The patient did not consume alcohol and did not report the introduction of a new medication. A skin rash compatible with syphilitic roseola and generalized adenopathy were found. The liver workup showed alanine aminotransferase (ALT) at 1984 U/L, aspartate aminotransferase (AST) at 1377 U/L, total bilirubin at 221 μmol/L, alkaline phosphatase activity (APL) at 419 U/L, gamma glutamyl transferase activity (GGT) at 229 U/L and a prothrombin concentration at 73%. The search for the most common etiologies of acute hepatitis was negative. Syphilitic serology was positive with a Treponema Pallidum Hemagglutinations Assay (TPHA) titration of 5120 IU and Veneral Disease Research Laboratory (VDRL) of 64 IU. Abdominal ultrasound revealed only homogeneous hepatomegaly and splenomegaly with no focal lesions. Other sexually transmitted infections (STI) were negative and her partner had positive syphilis serology. After a single dose of Benzathine benzylpenicillin, the clinical signs regressed after one week and the hepatic balance tended to normalize 20 days later. Conclusion: This highlights the need for a high index of suspicion for syphilitic hepatitis in sexually active patients presenting with acute hepatitis associated with a cutaneous rash.

Colorectal cancer screening in countries of European Council outside of the EU-28

AIM: To provide an update on colorectal cancer(CRC) screening programmes in non-European Union(EU)-28 Council of Europe member states as of December 2015. METHODS: The mission of the Council of Europe is to protect and promote human rights in its 47 member countries. Its 19 non-EU member states are Albania, Andorra, Armenia, Azerbaijan, Bosnia and Herzegovina, Republika Srpska, Georgia, Iceland, Liechtenstein, Republic of Moldova, Monaco, Montenegro, Norway, Russian Federation, San Marino, Serbia, Switzerland, FYR of Macedonia, Turkey, and Ukraine(EU-19). The main data source were GLOBOCAN, IARC, WHO, EUCAN, NORDCAN, ENCR, volume X of the CI5, the ministerial and Public Health Agency websites of the individual countries, Pub Med, EMBASE, registries of some websites and the www.cochranelibrary.com, Scopus, www.clinicaltrials.gov, www.clinicaltrialsregister.eu, Research gate, Google and data extracted from screening programme results. RESULTS: Our results show that epidemiological data quality varies broadly between EU-28 and EU-19 countries. In terms of incidence, only 30% of EU-19 countries rank high in data quality as opposed to 86% of EU-28 states. The same applies to mortality data, since 52% of EU-19 countries as against all EU-28 countries are found in the high ranks. Assessment of the method of collection of incidence data showed that only 32% of EU-19 countries are found in the top three quality classes as against 89% of EU-28 countries. For the mortality data, 63% of EU-19 countries are found in the highest ranks as opposed to all EU-28 member states. Interestingly, comparison of neighbouring countries offering regional screening shows, for instance, that incidence and mortality rates are respectively 38.9 and 13.0 in Norway and 29.2 and10.9 in Sweden, whereas in Finland, where a national organised programme is available, they are respectively 23.5 and 9.3. CONCLUSION: Cancer screening should be viewed as a key health care tool, also because investing in screening protects the weakest in the population, decreases the social burden of cancer, and reduces all types of health care costs, including those for radical surgery, long-term hospitalisation, and chemotherapy.

Final results of a 2:1 control-case observational study using interferon beta and interleukin-2,in addition to first-line hormone therapy,in estrogen receptor-positive,endocrine-responsive metastatic breast cancer patients

Aim:We conducted a pilot study that combines immunotherapy(cyclic interleukin-2 interferon-beta sequence)and hormone therapy(HT)to overcome endocrine resistance in metastatic breast cancer.Methods:The final results of a 2:1 control-case retrospective observational study are here shown following 22 additional months of postoperative follow-up and 6 further controls.There were 95 controls and 42 cases in total.The 95 controls were ER+/HER2-metastatic breast cancer patients who underwent first-line HT with aromatase inhibitors(AIs)or fulvestrant.Twenty-eight of them(28.9%)also received biological drugs including cyclin kinase inhibitors(CKIs).The 42 cases were ER+metastatic breast cancer patients who received interferon beta-interleukin-2 immunotherapy in addition to first-line HT.Selective estrogen receptor modulators/down-regulators(SERMs/SERDs)were used for HT in 39(92.9%)of them and AIs in the remaining 3.Results:Median progression-free survival(PFS)and overall survival(OS)were significantly longer in the 42 studied patients who received hormone immunotherapy(HIT)than in the 95 controls(median time 33 vs.18 months,P=0.002,and 81 vs.62 months,P=0.019).In the analysis adjusted for disease-free interval(DFI),hormone receptor,HER2 status,visceral involvement,AIs,and biological therapy,the PFS and OS hazard ratio(HR)further increased in favor of the 42 cases(P=0.004 and P=0.044 respectively).In the same ER+/HER2-metastatic breast cancer patients treated with both AIs and CKIs,a median PFS ranging from 25.3 to 28.18 months and a median OS of 37.5 months were observed.Conclusions:This study strongly suggests multi-center randomized clinical trials should be performed to enter our proposed immunotherapy into clinical practice.

Assessing resources for implementing a community directed intervention (CDI) strategy in delivering multiple health interventions in urban poor communities in Southwestern Nigeria: a qualitative study

Background:Many simple,affordable and effective disease control measures have had limited impact due to poor access especially by the poorer populations(urban and rural)and inadequate community participation.A proven strategy to address the problem of access to health interventions is the Community Directed Interventions(CDI)approach,which has been used successfully in rural areas.This study was carried out to assess resources for the use of a CDI strategy in delivering health interventions in poorly-served urban communities in Ibadan,Nigeria.Methods:A formative study was carried out in eight urban poor communities in the Ibadan metropolis in the Oyo State.Qualitative methods comprising 12 focus group discussions(FGDs)with community members and 73 key informant interviews(KIIs)with community leaders,programme managers,community-based organisations(CBOs),non-government organisations(NGOs)and other stakeholders at federal,state and local government levels were used to collect data to determine prevalent diseases and healthcare delivery services,as well as to explore the potential resources for a CDI strategy.All interviews were audio recorded.Content analysis was used to analyse the data.Results:Malaria,upper respiratory tract infection,diarrhoea and measles were found to be prevalent in children,while hypertension and diabetes topped the list of diseases among adults.Healthcare was financed mainly by out-of-pocket expenses.Cost and location were identified as hindrances to utilisation of health facilities;informal cooperatives(esusu)were available to support those who could not pay for care.Immunisation,nutrition,reproductive health,tuberculosis(TB)and leprosy,environmental health,malaria and HIV/AIDs control programmes were the ongoing interventions.Delivery strategies included house-to-house,home-based treatment,health education and campaigns.Community participation in the planning,implementation and monitoring of development projects was reported as common practice.The resources available for these activities and which constitute potential resources for the CDI process include community volunteers,CBOs and NGOs.Others are landlords;professional,women and youth associations;social clubs,religious organisations and the available health facilities.Conclusion:This study’s findings support the feasibility of using the CDI process in delivering health interventions in urban poor communities and show that potential resources for the strategy abound in the communities.