Lymphoepithelioma-like hepatocellular carcinoma: Case report and review of the literature

Lymphoepithelioma-like hepatocellular carcinoma(LELHCC) is a rare form of undifferentiated carcinoma of the liver characterized by the presence of an abundant lymphoid infiltrate. Here,a case of LEL-HCC is described. An 81-year-old woman with a chronic hepatitis C infection was referred to the general surgery department of our hospital in August 2013 with a diagnosis of HCC. A past ultrasound examination had revealed a 60 mm-diameter nodular lesion in the third segment of the liver. After a needle biopsy,the lesion was diagnosed as HCC. The patient underwent surgery with a liver segmentectomy. Two additional nodes on the gastric wall were detected during the surgical operation. The histology of the removed specimen showed a poorly differentiated HCC with significant lymphoid stroma. Immunohistochemical studies revealed that the epithelial component was reactive for CK CAM5.2,CK8,CK18,CEA(polyclonal) and was focally positive for hepar-1 and that the lymphoid infiltrate was positive for CD3,CD4 and CD8. The tumor cells were negative for Epstein-Barr virus. The gastric nodes were ultimately determined to be two small gastrointestinal stromal tumors(GISTs).The synchronous occurrence of HCC and GIST is another very uncommon finding rarely described in the literature. Here,we report the clinicopathological features of our case,along with a review of the few cases present in the literature.

Juvenile autoimmune hepatitis: Spectrum of the disease

Juvenile autoimmune hepatitis(JAIH) is a progressive inflammatory liver disease, affecting mainly young girls, from infancy to late adolescence, characterized by active liver damage, as shown by high serum activity of aminotransferases, by elevated immunoglobulin G levels, high titers of serum non organ-specific andorgan-specific autoantibodies, and by interface hepatitis on liver biopsy. It is a multifactorial disease of unknown etiology in which environmental factors act as a trigger in genetically predisposed individuals. Two types of JAIH are identified according to the autoan-tibody panel detected at diagnosis: AIH-1, characterized by the presence of anti-smooth muscle antibody and/or antinuclear antibody and AIH-2, by anti-liver-kidney microsomal antibody type 1 and/or by the presence of anti-liver cytosol type 1 antibody. Epidemiological distribution, genetic markers, clinical presentation and pattern of serum cytokines differentiate the two types of AIH suggesting possible pathogenetic mechanisms. The most effective therapy for AIH is pharmacological suppression of the immune response. Treatment should be started as soon as the diagnosis is made to avoid severe liver damage and progression of fibrosis. The aim of this review is to outline the most significant and peculiar features of JAIH, based largely on our own personal database and on a review of current literature.

Clinical epidemiology of chronic viral hepatitis B:A Tuscany real-world large-scale cohort study

AIM To build a regional database of chronic patients to define the clinical epidemiology of hepatitis B virus(HBV)-infected patients in the Tuscan public health care system.METHODS This study used a cross-sectional cohort design. We evaluated chronic viral hepatitis patients with HBV referred to the outpatient services of 16 hospital units. Information in the case report forms included main demographic data, blood chemistry data, viral hepatitis markers, instrumental evaluations, and eligibility for treatment or ongoing therapy and liver transplantation. RESULTS Of 4015 chronic viral hepatitis patients, 1096(27.3%) were HBV infected. The case report form was correctly completed for only 833 patients(64% males, 36% females; mean age 50.1 ± 15.4). Of these HBV-infected patients, 73% were Caucasian, 21% Asian, 4% Central African, 1% North African and 1% American. Stratifying patients by age and nationality, we found that 21.7% of HBV-infected patients were aged < 34 years(only 2.8% were Italian). The most represented routes of transmission were nosocomial/dental procedures(23%), mother-to-child(17%) and sexual transmission(12%). The most represented HBV genotypes were D(72%) and A(14%). Of the patients, 24.7% of patients were HBe Ag positive, and 75.3% were HBe Ag negative. Of the HBV patients 7% were anti-HDV positive. In the whole cohort, 26.9% were cirrhotic(35.8% aged < 45 years), and 47% were eligible for or currently undergoing treatment, of whom 41.9 % were cirrhotic. CONCLUSION Only 27.3% of chronic viral hepatitis patients were HBV infected. Our results provide evidence of HBV infection in people aged < 34 years, especially in the foreign population not protected by vaccination. In our cohort of patients, liver cirrhosis was also found in young adults.

Different Clinical Phenotypes in Adams-Oliver Syndrome Conservative Approach to Aplasia Cutis: A Report of Two Cases

Adams-Oliver Syndrome (AOS) is a rare genetic disease characterized by combination of aplasia cutis congenita (ACC) and terminal transverse limb defects (TTLD), often accompanied by defects in scalp and skull ossification. Different clinical phenotypes may be related to variable severity both of aplasia cutis and TTLD, and of minor clinical features as cutis marmorata telangiectatica congenita (CMTC), congenital cardiac defect and vascular anomalies. The treatment is multidisciplinary: dermatologic, orthopedic and surgical consult should be required. It still remains unclear how to treat patients with a large skin defect that can‘t be closed primarly and may require both surgical and conservative management. We report two cases of AOS with typical limb defects and an area of aplasia cutis over vertex of the scalp managed conservatively with two different dermatologic devices.

Maternal PAPP-A Levels at 11 - 13 Weeks of Gestation Predict Foetal and Neonatal Growth

Recent reports suggest that maternal serum levels of pregnancy-associated plasma protein A (PAPP-A) may predict perinatal outcome. PAPP-A is a syncytiotrophoblast derived protease for insulin-like growth factor binding protein (IGFBP4);its protease activity cleaves complexed growth factor binding protein increasing insulin-like growth factor I (IGF-I) bioavailability. The aim of our study was to evaluate the correlation between maternal PAPP-A serum levels and neonatal growth. We analysed 100 full term and preterm (30 - 36 weeks) small for gestational age (SGA) and adequate for gestational age (AGA) babies whose mothers had been tested for serum PAPP-A at 11 - 13 weeks of gestation. We found a significant positive correlation between maternal PAPP-A and neonatal weight, length, and head circumference at birth in both term and preterm infants. Low maternal PAPP-A serum levels (maternal PAPP-A < 0.5) were associated with small for gestational age neonates. A significant positive correlation was also evident between maternal PAPP-A and babies’ growth parameters at 6 months of age. Our results suggest that maternal levels of PAPP-A in early pregnancy affect growth during both foetal and early postnatal life.

Digital liver biopsy:Bio-imaging of fatty liver for translational and clinical research

The rapidly growing field of functional, molecular and structural bio-imaging is providing an extraordinary new opportunity to overcome the limits of invasive liver biopsy and introduce a "digital biopsy" for in vivo study of liver pathophysiology. To foster the application of bio-imaging in clinical and translational research, there is a need to standardize the methods of both acquisition and the storage of the bio-images of the liver. It can be hoped that the combination of digital, liquid and histologic liver biopsies will provide an innovative synergistic tri-dimensional approach to identifying new aetiologies, diagnostic and prognostic biomarkers and therapeutic targets for the optimization of personalized therapy of liver diseases and liver cancer. A group of experts of different disciplines(Special Interest Group for Personalized Hepatology of the Italian Association for the Study of the Liver, Institute for Biostructures and Bio-imaging of the National Research Council and Bio-banking and Biomolecular Resources Research Infrastructure) discussed criteria, methods and guidelines for facilitating the requisite application of data collection. This manuscript provides a multi-Author review of the issue with special focus on fatty liver.

Deep endometriosis with pericolic lymph node involvement: A case report and literature review

Deep infiltrating endometriosis is an often-painful disorder affecting women during their reproductive years that usually involves the structures of the pelvis and frequently the gastrointestinal tract.We present the case of a 37-year-old female patient with an endometrial growth on the sigmoid colon wall causing pain,diarrhea and the presence of blood in the feces.The histology of the removed specimen also revealed the involvement of the utero-vesical fold,the recto-vaginal septum and a pericolic lymph node,which are all quite uncommon findings.To identify the endometrial cells,we performed immunohistochemical staining for CD10and the estrogen and progesterone receptors.

FOLFIRINOX and translational studies: Towards personalized therapy in pancreatic cancer

Pancreatic cancer is an extremely aggressive disease; although progress has been made in the last few years, the prognosis of these patients remains dismal. FOLFIRINOX is now considered a standard treatment in first-line setting, since it demonstrated an improved overall and progression-free survival vs gemcitabine alone. However, the enthusiasm over the benefit of this three-drug regimen is tempered by the associated increased toxicity profile, and many efforts have been made to improve the feasibility of this schedule. After a more recent phase Ⅲ trial showing an improved outcome over gemcitabine, the combination of gemcitabine/nab-paclitaxel emerged as another standard first-line treatment. However, this treatment is also associated with more side effects. In addition, despite initial promising data on the predictive role of SPARClevels, recent studies showed that these levels are not associated with nab-paclitaxel efficacy. The choice to use this treatment over FOLFIRINOX is therefore a topic of debate, also because no validated biomarkers to guide FOLFIRINOX treatment are available. In the era of actionable mutations and target agents it would be desirable to identify molecular factors or biomarkers to predict response to therapy in order to maximize the efficacy of treatment and avoid useless toxic effects for non-responding patients. However, until today the milestone of treatment for pancreatic cancer remains chemotherapy combinations, without predictive or monitoring tools existing to optimize therapy. This review analyzes the state-of-the-art treatments, promises and limitations of targeted therapies, ongoing trials and future perspectives, including potential role of microR NAs as predictive biomarkers.

Surveillance for hepatocellular carcinoma in chronic viral hepatitis:Is it time to personalize it?

Surveillance with abdominal ultrasound with or without alpha-fetoprotein is recommended by clinical practice guidelines for patients who are considered to be at risk of developing hepatocellular carcinoma(HCC),including those with cirrhosis,advanced fibrosis and special subgroups of chronic hepatitis B(CHB).Application of the standard surveillance strategy to all patients with chronic liver disease(CLD)with or without cirrhosis imposes major sustainability and economic burdens on healthcare systems.Thus,a number of HCC risk scores were constructed,mainly from Asian cohorts,to stratify the HCC prediction in patients with CHB.Similarly,even if less than for CHB,a few scoring systems were developed for chronic hepatitis C patients or cirrhotic patients with CLD of different etiologies.Recently,a few newsworthy HCC-risk algorithms were developed for patients with cirrhosis using the combination of serologic HCC markers and clinical parameters.Overall,the HCC risk stratification appears at hand by several validated multiple score systems,but their optimal performance is obtained only in populations who show highly homogenous clinic-pathologic,epidemiologic,etiologic and therapeutic characteristics and this limitation poses a major drawback to their sustainable use in clinical practice.A better understanding of the dynamic process driving the progression from CLD to HCC derived from studies based on molecular approaches and genetics,epigenetics and liquid biopsy will enable the identification of new biomarkers to define the individual risk of HCC in the near future,with the possibility to achieve a real and cost/effective personalization of surveillance.

Which surgery for ground glass opacity lung nodules?

Objective:Pulmonary ground glass opacity(GGO)nodules represent a significant dilemma in oncology since its diagnosis in clinical practice has increased because of growing application of low dose computed tomography and screening program.The aim of this study is to analyze the clinical and pathological features,the overall survival(OS)and disease-free interval(DFI)in surgically resected solitary ground glass nodules in order to assess the surgical treatment of choice.Methods:We retrospectively analyzed 49 patients(M/F=25/24)with a mean age of 67.7(range,40-81)years who underwent lung resection for solitary GGO nodules among 570 reviewed CT of patients who were treated for lung neoplasms between 2010 and 2016.The cohort included 22 pure GGO nodules and 27 part solid GGOs(also called mixed GGOs).Results:Median maximum diameter of GGOs,defined as the largest axial diameter of the lesion on the lung-window setting,was 17(range,5-30)mm.GGO nodules were removed by wedge resection,segmentectomy,or lobectomy in 17(35%),9(18%),and 23(47%)cases,respectively.Pathologic diagnosis was atypical adenomatous hyperplasia(AAH),adenocarcinoma in situ(AIS),minimally invasive adenocarcinoma(MIA),invasive adenocarcinoma(IA)or multifocal adenocarcinoma(MAC)in 4(8.2%),9(18.4%),11(22.4%),22(44.9%)and 3(6.1%)cases,respectively.With a median follow up of 47 months the OS and DFI of the entire cohort was 46.3 and 43 months,respectively.The histotype(P=0.008),the dimension of GGO(P=0.014)and the PET-SUV max(P=0.001)were independent prognostic factors of worse survival.Sex,age,previous lung surgery,type of surgical resection and the mediastinal lymph-node evaluation did not impact on OS and DFI.Analyzing the 22 pure GGO nodules,we found a 3-year OS and DFI of 98%and 100%respectively,significantly different from 80%and 75%respectively of part-solid GGOs(log-rank P=0.043 and P=0.011).Conclusion:Our data suggest an indolent behaviour of tumour presenting as solitary GGO nodules,especially in case of pure GGOs.In our series wedge resections guarantee the same results in terms of OS and DFI when compared to lobectomies.Sublobar resections without mediastinal lymph-nodes evaluation represent the treatment of choice for pure-GGO.More studies are needed to assess its role for part-solid GGO nodules.

First-line pazopanib in patients with advanced non-clear cell renal carcinoma:An Italian case series

BACKGROUND Non-clear cell(ncc)metastatic renal-cell carcinoma(RCC)has dismal results with standard systemic therapies and a generally worse prognosis when compared to its clear-cell counterpart.New systemic combination therapies have emerged for metastatic RCC(mRCC),but the pivotal phase III trials excluded patients with nccRCC,which constitute about 30%of metastatic RCC cases.AIM To provide a piece of real-life evidence on the use of pazopanib in this patient subgroup.METHODS The present study is a multicenter retrospective observational analysis aiming to assess the activity,efficacy,and safety of pazopanib as first-line therapy for advanced nccRCC patients treated in a real-life setting.RESULTS Overall,48 patients were included.At the median follow-up of 40.6 mo,the objective response rate was 27.1%,the disease control rate was 83.3%,and the median progression-free survival and overall survival were 12.3(95%confidence interval[CI]:3.6-20.9)and 27.7(95%CI:18.2-37.1)mo,respectively.Grade 3 adverse events occurred in 20%of patients,and no grade 4 or 5 toxicities were found.CONCLUSION Pazopanib should be considered as a good first-line option for metastatic RCC with variant histology.

Health effects of air pollution:a Southern European perspective

Objective:To summarize the main updated evidence about the health effects of air pollution,with a special focus on Southern Europe.Data sources:Literature was obtained through PubMed Central and the official websites of European Agencies and Scientific Societies.Study selection:Recent shreds of evidence about the health effects of air pollution coming from international reports and original research were collected and described in this review.Results:Air pollution is an avoidable risk factor that causes a huge burden for society,in terms of death,health disorders,and huge socio-economic costs.The southern European countries face a more threatening problem because they experience the effects of both anthropogenic pollutants and natural dusts(particulate matter[PM]).The European Environment Agency reported the number of premature deaths in the 28 countries of the European Union attributable to air pollutant exposure in the year 2016:374,000 for PM2.5,68,000 for nitrogen dioxide,and 14,000 for ozone.In Italy,time series and analytical epidemiological studies showed increased cardiorespiratory hospital admissions and mortality,as well as increased risk of respiratory diseases in people living in urban areas.Conclusions:Based on abundant evidence,the World Health Organization,which hosts the Global Alliance against Chronic Respiratory Diseases(GARD),the scientific respiratory societies,and the patients’associations,as well as others in the health sector,must increase their engagement in advocacy for clean air policies.

Prognostic factors and efficacy of GDP-R therapy in refractory/relapsed diffuse large B-cell lymphomas not eligible for high-dose therapy

Aim:The main aim of the present study was to evaluate the overall survival(OS)and time to treatment failure(TTF)in a cohort of relapsed/refractory diffuse large B-cell lymphomas(DLBCLs)not eligible for high-dose therapy(HDT)treated with gemcitabine in association with dexamethasone,cisplatin and rituximab(GDP-R)protocol.The secondary aim was to identify the prognostic factors impacting OS and TTF.Methods:The authors retrospectively analyzed 45 patients with refractory/relapsed DLBCLs treated with GDP-R.Results:Overall response rate(ORR)was 48.8%;complete response 15/45(33.3%),partial response 7/45(15.5%).Response was influenced by the number of previous therapies administered and International Prognostic Index(IPI)value.Although no significant impact occurred with regard to OS,patients pre-treated with 2 or<2 chemotherapeutic regimens had better ORR(P=0.014)and a longer TTF(P=0.029 in multivariate Cox model).IPI value also influenced TTF.Patients with<2 IPI value had significantly more prolonged TTF than the other ones(P=0.048 in multivariate Cox model).Treatment was well-tolerated,with the majority of patients treated on out-patient modality.GDP-R regimen represents a valid treatment for aggressive relapsed/refractory B-cell lymphoma not eligible for HDT thanks to its efficacy and good toxic profile.Conclusion:The number of previous chemotherapeutic regimens and IPI value select those who benefit more from this treatment.

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.

Systemic treatment of advanced, metastatic, medullary thyroid carcinoma

Medullary thyroid carcinoma(MTC)is a rare endocrine tumor,which arises from thyroid parafollicular C cells.Through its ability to metastasize by blood and lymphatic vessels,it can show a more aggressive clinical behavior than differentiated thyroid cancers.Mutation of RET gene is the main molecular alteration involved in MTC origin.In the case of germline RET mutation,MTC can be inherited in an autosomal dominant way and show three different phenotypes:familial medullary thyroid carcinoma and multiple endocrine neoplasia types IIA and IIB.In addition,in sporadic cases,somatic RET mutation remains the key molecular alteration in most of cases.Total thyroidectomy with prophylactic or therapeutic central compartment lymph nodes dissection is the surgical treatment of choice.Further surgical treatments and local therapies should be used in the case of single or few local or distant metastasis.However,in cases with large metastatic spread of the disease,particularly in those with significant tumor progression,additional systemic treatments are needed.In this review,we discuss the key points of systemic treatment in advanced,metastatic MTC.We provide an update on the main aspects(from biological rationale to clinical experience)of each treatment,focusing our attention on the drugs used in clinical practice in the last years.Finally,we give insights about the emerging treatments from highly selective RET inhibitors to new radionuclide therapy.

Choroidal vascularity index in thyroidassociated ophthalmopathy:a crosssectional study

Background:Hemodynamic changes have been observed in patients with Graves'disease.The aim of our study was to evaluate choroidal vascular change using the choroidal vascularity index(CVi)in patients with thyroid-associated ophthalmopathy(TAO).Methods:In this cross-sectional observational study,40 patients affected by TAO were recruited.Forty healthy individuals,matched for age and sex,served as controls.Foveal enhanced-depth imaging optical coherence tomography scans were obtained from all participants.Images were binarized using the ImageJ software and luminal area(LA)and total choroidal area(TCA)were measured.CVI was calculated as the proportion of LA to TCA.The relation between CVI or subfoveal choroidal thickness(SFCT)and clinical activity score,exophthalmometric value,diplopia status,gender,and age was evaluated.Results:CVI was significantly higher in patients with TAO(P=0.004).No significant difference was observed in SFCT(P=0.200)and TCA(P=0.153)comparing TAO patients and healthy controls.LA was significantly higher in TAO group(P=0.045).On multiple regression analysis,CVI was associated with TCA(P=0.043).No association Was found between SFCT or CVI and TCA,clinical activity score,exophthalmometric value,Inami value,diplopia status,genderorage(P>0.05).Conclusions:This is the first study that has demonstrated an increase in CVI in eyes with TAO compared with healthy controls and has assessed its association with clinical features.

核医学在甲状腺良性疾病临床处治中的应用(第1部分):甲状腺功能亢进症

甲状腺良性疾病,尤其是甲状腺功能亢进症(简称甲亢)和甲状腺功能减退症(简称甲减),是最常见的内分泌疾病。甲亢常见的病因是自身免疫性甲亢(格雷夫斯病,即GD)、毒性多结节性甲状腺肿(TMNG)、毒性甲状腺腺瘤(TAs);其他少见病因包括破坏性甲状腺炎(胺碘酮导致的甲状腺功能异常)和人为甲亢。GD主要由促甲状腺激素受体抗体(TRAb)引起;TMNG和TAs由体细胞功能激活获得突变引起。甲亢患者典型的实验室表现为促甲状腺激素(TSH)降低,游离三碘甲状腺原氨酸(FT3)和游离甲状腺素(FT4)升高,以及GD患者TSH受体自身抗体升高。超声检查主要用于明确甲状腺大小、血供以及甲状腺结节的位置、大小、数目及影像特征。甲状腺超声和实验室检查是明确甲亢病因的一线诊断方法。甲状腺显像(^(131)I或99TcmO4-甲状腺显像)可用于鉴别不同类型的甲亢,为^(131)I治疗提供策略指导。甲状腺显像可帮助鉴别GD、TMNG、TAs和破坏性甲状腺炎。^(99)Tc^(m)O_(4)^(-)可鉴别胺碘酮导致的1型和2型甲亢。测定甲状腺摄碘率(RAIU)有助于明确甲亢^(131)I治疗的放射性活度。治疗甲亢的方案主要包括抗甲状腺药物(ATD)治疗、手术或^(131)I治疗。当患者ATD治疗失败、或有手术治疗禁忌或拒绝手术,可以考虑^(131)I治疗。对于TMNG或TAs患者,^(131)I治疗目的在于恢复正常甲状腺功能。对于GD患者,^(131)I治疗的目的在于诱发甲减,这种状态易通过口服甲状腺激素替代疗法治疗。可根据甲状腺大小和RAIU的计算剂量法指导^(131)I治疗的放射性活度。^(131)I治疗的早期毒性及不良反应(甲状腺床区轻微疼痛)可通过非甾体抗炎药来处理;晚期毒性及不良反应主要是甲减和辐射诱导的恶性肿瘤(发生率极低)。

Choroidal vascularity index in thyroidassociated ophthalmopathy:a crosssectional study

Background:Hemodynamic changes have been observed in patients with Graves’disease.The aim of our study was to evaluate choroidal vascular change using the choroidal vascularity index(CVI)in patients with thyroidassociated ophthalmopathy(TAO).Methods:In this cross-sectional observational study,40 patients affected by TAO were recruited.Forty healthy individuals,matched for age and sex,served as controls.Foveal enhanced-depth imaging optical coherence tomography scans were obtained from all participants.Images were binarized using the ImageJ software and luminal area(LA)and total choroidal area(TCA)were measured.CVI was calculated as the proportion of LA to TCA.The relation between CVI or subfoveal choroidal thickness(SFCT)and clinical activity score,exophthalmometric value,diplopia status,gender,and age was evaluated.Results:CVI was significantly higher in patients with TAO(P=0.004).No significant difference was observed in SFCT(P=0.200)and TCA(P=0.153)comparing TAO patients and healthy controls.LA was significantly higher in TAO group(P=0.045).On multiple regression analysis,CVI was associated with TCA(P=0.043).No association was found between SFCT or CVI and TCA,clinical activity score,exophthalmometric value,Inami value,diplopia status,gender or age(P>0.05).Conclusions:This is the first study that has demonstrated an increase in CVI in eyes with TAO compared with healthy controls and has assessed its association with clinical features.

Hypodysfibrinogenemia in a young patient withrecurrent strokes

Stroke is a complex disease, but in some instances is the direct result of a monogenic disease. Here we report the case of a 44-year-old Italian man who experienced recurrent transitory ischemic attacks and strokes. He also had right fetal-type posterior cerebral artery. He was diagnosed with congenital hypodysfibrinogenemia due to a mutation leading to a truncated fibrinogen gamma chain. Further studies are needed to better elucidate the links between fibrinogen dysfunction and stroke. Hypodysfibrinogenemia should be included among the monogenic diseases associated with ischemic stroke. Physicians should be aware of this condition, which may be detectable on routine assays.