Expanding indications for chronic hepatitis B treatment: Is it really desirable to treat everyone?

Chronic viral hepatitis causes an increased risk of progressive liver disease and hepatocellular carcinoma.On the wave of the World Health Organization’s goal to reduce new cases and deaths from hepatitis B and C by 2030,there is an increasing call to expand the indications for treatment of chronic hepatitis B.Currently,the main goal of treatment is to achieve a functional cure due to the inability of current drugs to completely eradicate the virus.There are still many discrepancies between available guidelines in terms of eligibility for treatment as well as an uncertainty about the appropriate treatment duration.This editorial addresses key questions about the topic and whether indications for treatment should be expanded.

Synergistic effect of interleukin-10-receptor variants in a case of early-onset ulcerative colitis

AIM:To investigated the molecular cause of very early-onset ulcerative colitis(UC)in an 18-mo-old affected child.METHODS:We analysed the interleukin-10(IL10)receptor genes at the DNA and RNA level in the proband and his relatives.Beta catenin and tumor necrosis factor-α(TNFα)receptors were analysed in the proteins extracted from peripheral blood cells of the proband,his relatives and familial adenomatous polyposis(FAP)and PTEN hamartoma tumor syndrome(PHTS)patients.Samples were also collected from the proband’s inflamed colorectal mucosa and compared to healthy and tumour mucosa collected from a FAP patient and patients affected by sporadic colorectal cancer(CRC).Finally,we examined mesalazine and azathioprine effects on primary fibroblasts stabilised from UC and FAP patients.RESULTS:Our patient was a compound heterozygote for the IL10RB E47K polymorphism,inherited from his father,and for a novel point mutation within the IL10RA promoter(the-413G->T),inherited from his mother.Beta catenin and tumour necrosis factorαreceptors-Ⅰ(TNFRI)protein were both over-expressed in peripheral blood cells of the proband’s relatives more than the proband.However,TNFRII was over-expressed only in the proband.Finally,both TNFα-receptors were shown to be under-expressed in the inflamed colon mucosa and colorectal cancer tissue compared to healthy colon mucosa.Consistent with this observation,mesalazine and azathioprine induced,in primary fibroblasts,IL10RB and TNFRII over-expression and TNFRI and TNFαunder-expression.We suggest thatβ-catenin and TNFRI protein expression in peripheral blood cells could represent molecular markers of sub-clinical disease in apparently healthy relatives of patients with early-onset UC.CONCLUSION:A synergistic effect of several variant alleles of the IL10 receptor genes,inherited in a Mende-lian manner,is involved in UC onset in this young child.

Pediatric gastrointestinal bleeding: Perspectives from the Italian Society of Pediatric Gastroenterology

There are many causes of gastrointestinal bleeding(GIB) in children, and this condition is not rare, having a reported incidence of 6.4%. Causes vary with age, but show considerable overlap; moreover, while many of the causes in the pediatric population are similar to those in adults, some lesions are unique to children. The diagnostic approach for pediatric GIB includes definition of the etiology, localization of the bleeding site and determination of the severity of bleeding; timely and accurate diagnosis is necessary to reduce morbidity and mortality. To assist medical care providers in the evaluation and management of children with GIB, the "Gastro-Ped Bleed Team" of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition(SIGENP) carried out a systematic search on MEDLINE via Pub Med(http://www.ncbi.nlm.nih.gov/pubmed/) to identify all articles published in English from January 1990 to 2016; the following key words were used to conduct the electronic search: "upper GIB" and "pediatric" [all fields]; "lower GIB" and "pediatric" [all fields]; "obscure GIB" and "pediatric" [all fields]; "GIB" and "endoscopy" [all fields]; "GIB" and "therapy" [all fields]. The identified publications included articles describing randomized controlled trials, reviews, case reports, cohort studies, casecontrol studies and observational studies. References from the pertinent articles were also reviewed. This paper expresses a position statement of SIGENP that can have an immediate impact on clinical practice and for which sufficient evidence is not available in literature. The experts participating in this effort were selected according to their expertise and professional qualifications.

Expression of Interleukin-11 and Interleukin-11 receptor a in human colorectal adenocarcinoma; Immunohistochemical analyses and correlation with clinicopathological factors

AIM: There is strong evidence that interleukin-11 (IL-11) is involved in the regulation of tumor progression, cellular growth and differentiation. Recently, interleukin-11 receptor (IL-11R) has been detected on some cancer cells. In this study, we investigated the expression of IL-11 and IL-11R in colorectal adenocarcinoma. METHODS: To elucidate the involvement of IL-11 and IL-11Ra in human intestinal adenocarcinomas, we examined 115 cases of surgically resected human colonic adenocarcinoma and 11 cases of adenoma by immuno-histochemistry and Western blotting. RESULTS: Among 115 cases of adenocarcinoma, 100 cases (87.0%) showed positive staining in the cytoplasm of carcinoma cells for the IL-11, and 87 cases (75.6%) were positive for the IL-11Ra. Six cases (54.5%) and four cases (36.4%) of 11 adenomas were positive for IL-11 and IL-11Ra, respectively. The expression of IL-11Ra correlated with the histological differentiation (P=0.033503), the depth of tumor invasion (P=0.006395), Dukes' classification (P= 0.015648) and lymphatic invasion (P=0.003865). However, the expression of IL-11Ra was not correlated with the venous invasion and the presence of lymph node metastasis. The expression of IL-11 was not correlated with any clinicopathological factors. In Western blot analysis, two human colorectal carcinoma cell lines and four tissues of surgically resected human carcinoma expressed both IL-11 and IL-11Ra proteins. CONCLUSION: IL-11 and IL-11Ra are highly expressed in human colorectal adenocarcinoma and the IL-11Ra expression is correlated with clinicopathological factors. These findings suggest that the expression of IL-11Ra is an important factor for the invasion of human colorectal adenocarcinoma.

Mitral peak early diastolic filling velocity to deceleration time ratio as a predictor of prognosis in patients with chronic heart failure and preserved or reduced ejection fraction

ObjectiveDoppler 导出僧帽形的山峰到减速时间比率(E/DT ) 的早心脏舒张的充满速度为在一般人口预言预后作为参数被建议了。这研究有希望地在就医的病人在临床的、常规 echocardiographic 和 mitral-Doppler 变量上调查 E/DT 的增长的预示的值因为患心脏代偿失调的心失败(HF ).MethodsWe 分析了 95 个 HF 病人(吝啬的年龄 64.8 &#x000b1；12.2 年) 从 2010 年 1 月在我们的机构就医了到 2012 年 3 月。主要端点是心脏的死亡或住院，无论哪个首先发生了。考克斯回归分析被执行识别 outcomes.ResultsDuring 后续的重要预言者(中部 37.7 个月) 13 个病人死了， 44 为一个心脏的事件被就医。在 univariable 分析，纽约心协会(NYHA ) 功能的班， furosemide 剂量，侧面的有三尖的环形的飞机收缩旅行，减速时间和 E/DT 结果是预兆的。在 multivariable 分析， E/DT 是预后的唯一的预言者(危险比率 = 1.02， P = 0.018 ) ，把增长预示的信息给临床并且另外的 echocardio 图形的措施(从 15.4 ～ 25.2 的全球 chi 平方；P = 0.032 ).ConclusionsE/DT 在 HF 病人给独立、增长的预示的信息。

Selection of treatment modality for hepatocellular carcinoma according to the modified Japan Integrated Staging score

AIM: To compare the prognosis of patients who underwent hepatectomy and ablation using the modified Japan Integrated Staging score (mJIS).METHODS: We examined the clinicopathologic records and patient outcomes in 278 HCC patients including 226 undergoing hepatectomy and 52 undergoing ablation therapy.RESULTS: Cirrhosis was more frequent in the ablation group. Tumor size, number and presence of vascular invasion were significantly higher in the operation group compared to the ablation group. The local recurrence rate adjacent to treated lesions was significantly higher in the ablation group compared to the operation group (P < 0.05). The 3- and 5-year survival rates in the ablation and the operation group were 66% and 78%, and 50% and 63%, respectively, but not significantly different. Over 50% survival rates were observed in patients with a mJIS score of 0-2 in both groups. However, survival rates with a score of 3-5 in both groups were significantly lower.CONCLUSION: According to the mJIS system, both local treatments could be selected for patients with a score of 0-2. However, for patients with a score more than 3, liver transplantation might be a better option in patients with HCC.

Role of nuclear cardiology for guiding device therapy in patients with heart failure

Heart failure is a dynamic condition with high morbidity and mortality and its prognosis should be reassessed frequently, particularly in patients for whom critical treatment decisions may depend on the results of prognostication. In patients with heart failure, nuclear cardiology techniques are useful to establish the etiology and the severity of the disease, while fewer studies have explored the potential capability of nuclear cardiology to guide cardiac resynchronization therapy(CRT) and to select patients for implantable cardioverter defibrillators(ICD). Left ventricular synchrony may be assessed by radionuclide angiography or gated singlephoton emission computed tomography myocardial perfusion scintigraphy. These modalities have shown promise as predictors of CRT outcome using phase analysis. Combined assessment of myocardial viability and left ventricular dyssynchrony is feasible using positron emission tomography and could improve conventional response prediction criteria for CRT. Preliminary data also exists on integrated positron emission tomography/computed tomography approach for assessing myocardial viability, identifying the location of biventricular pacemaker leads, and obtaining left ventricular functional data, including contractile phase analysis. Finally, cardiac imaging with autonomic radiotracers may be useful in predicting CRT response and for identifying patients at risk for sudden cardiac death, therefore potentially offering a way to select patients for both CRT and ICD therapy. Prospective trials where imaging is combined with image-test driven therapy are needed to better define the role of nuclear cardiology for guiding device therapy in patients with heart failure.

Current applications of big data and machine learning in cardiology

Machine learning (ML) is a software solution with the ability of making predictions without prior explicit programming, aiding in the analysis of large amounts of data. These algorithms can be trained through supervised or unsupervised learning. Cardiology is one of the fields of medicine with the highest interest in its applications. They can facilitate every step of patient care, reducing the margin of error and contributing to precision medicine. In particular, ML has been proposed for cardiac imaging applications such as automated computation of scores, differentiation of prognostic phenotypes, quantification of heart function and segmentation of the heart. These tools have also demonstrated the capability of performing early and accurate detection of anomalies in electrocardiographic exams. ML algorithms can also contribute to cardiovascular risk assessment in different settings and perform predictions of cardiovascular events. Another interesting research avenue in this field is represented by genomic assessment of cardiovascular diseases. Therefore, ML could aid in making earlier diagnosis of disease, develop patient-tailored therapies and identify predictive characteristics in different pathologic conditions, leading to precision cardiology.

Migraine attack restores the response of vascular smooth muscle cells to nitric oxide but not to norepinephrine

AIM:To clarify whether the vasoconstrictory response is impaired and to study vascular function in patients with migraine during the headache attack.METHODS:We studied vascular reactivity in the resistance arteries by using the forearm perfusion technique associated with plethysmography.We measuredforearm blood flow by strain-gauge plethysmography during intra-brachial infusion of acetylcholine,sodium nitroprusside or norepinephrine in 11 controls and 13patients with migraine,11 of them(M) in the interval between the migraine attacks and 4 during a headache attack(MH).Written informed consent was obtained from patients and healthy controls,and the study was approved by the Ethics Committee of the University Federico Ⅱ.RESULTS:Compared to healthy control subjects,in patients with migraine studied during the interictal period,the vasodilating effect of acetylcholine,that acts through the stimulation of endothelial cells and the release of nitric oxide,was markedly reduced,but became normal during the headache attack(P<0.05by analysis of variance).The response to nitroprusside,which directly relaxes vascular smooth muscle cells(VSMCs),was depressed in patients with migraine studied during the interictal period,but normal during the headache attack(P<0.005).During norepinephrine infusion,forearm blood flow decreased in control subjects(-40% ± 5%,P<0.001).In contrast,in patients with migraine,either when studied during or free of the headache attack forearm blood flow did not change compared to the baseline value(-3%±13% and-10.4%±15%,P>0.05).CONCLUSION:In migrainers,the impaired relaxation of VSMCs is restored during the headache attack.The vasoconstrictory response is impaired and remains unchanged during the migraine attack.

Prevalence of functional gastrointestinal disorders in children with celiac disease on different types of gluten-free diets

BACKGROUND Functional gastrointestinal disorders(FGIDs)are common during the pediatric age.FGIDs are not related to biochemical or structural abnormalities.However,since they have a high prevalence,several studies have evaluated an overlap between FGIDs and organic diseases.Individuals with celiac disease(CD)have been shown to be at an increased risk for functional abdominal pain,even if they adhere well to a gluten-free diet(GFD).Little information is available for the pediatric age group.The aims of our study were to evaluate the prevalence of FGIDS in CD children 1 year after diagnosis and to compare the prevalence of FGIDs in CD children on a GFD with processed foods compared with those on a GFD with natural products.AIM To assess the prevalence of FGIDs in children with CD after 1 year of follow-up and to compare the prevalence of FGIDs in children with CD on a GFD with processed foods and in children on a GFD with natural products.METHODS We recruited pediatric patients aged 1-18 years with a new CD diagnosis.Participants were randomized to two groups:Group A on a GFD with processed foods(diet 1);and group B on a GFD with natural products(diet 2).Clinical monitoring,diet assessment and the questionnaire on pediatric gastrointestinal symptoms-Rome IV version were performed at diagnosis(T0)and after 12 mo of follow-up(T1).Dietary intake was assessed using a 3-d food diary record.Data from the diaries were evaluated using WinFood nutrient analysis software.We assessed the prevalence of FGIDs at T1 and the correlation with the type of GFD.RESULTS We registered 104 CD children,with 55 patients in group A(53.0%)and 49 patients in group B(47.0%).Initially,30 of the 55(54.5%)CD children were symptomatic in group A,while 25 of 49(51.0%)were symptomatic in group B.At T1,in spite of a low or negative serology for CD,FGIDs prevalence was 10/55(18.0%)in group A and 8/49(16.3%)in group B,with no statistically significant difference between the two groups(P=0.780).At T1 the macro-and micronutrient intake was similar across the two groups with no significant differences in nutrient analysis.However,in both groups at T1 we found that a lower prevalence of FGIDs(P=0.055)was associated with an inferior caloric(odds ratio=0.99,95%confidence interval:0.99-1.00)and fat(odds ratio=0.33,95%confidence interval:0.65-0.95)intake.CONCLUSION Our results showed that CD children on a GFD have gastrointestinal symptoms with an elevated prevalence of FGIDs.Our study suggests that developing FGIDs may be linked to caloric intake and percentage of food fat,but it does not change between a GFD with processed foods or a GFD with natural products.However,long-term monitoring is required to evaluate a correlation between FGIDs and various types of GFDs.

Variability of anti-human transglutaminase testing in celiac disease across Mediterranean countries

AIM To verify the precision and accuracy of transglutaminase antibodies(TGA)assays across Mediterranean countries.METHODS This study involved 8 referral centres for celiac disease(CD)in 7 Mediterranean countries.A central laboratory prepared 8 kits of 7 blinded and randomized serum samples,with a titrated amount of Human TGA Ig A.Each sample was analysed three times on three different days,with each centre running a total of 21tests.The results were included in a blindly coded report form,which was sent to the coordinator centre.The coordinator estimated the mean coefficient of Variation(Co Var=σ/μ),the mean accuracy(Accur=Vobserved-Vreal)and the mean percent variation(Var%=[(Vobserved-Vreal)/Vreal]×100).RESULTS The analysis showed that 79.17%of the mean variation fell between-25%and+25%of the expected value,with the accuracy and precision progressively increasing with higher titres of TGA.From values 1.25 times greater than the normal cut-off,the measurements were highly reliable.CONCLUSION TGA estimation is a crucial step for the diagnosis of CD;given its accuracy and precision,clinicians could be confident in establishing a diagnosis.

Cardiac remodeling in postischemic end-stage human hearts: Involvement of extracellular matrix and angiogenesis-related molecules

Background: Extracellular matrix (ECM) participates in heart growth and influences cardiac stem-cell differentiation and migration. The modification of ECM associated with cardiomyopathies is a complex process involving a cohort of proteins. ECM proteins are involved in the regulation of neoangiogenesis in physiological and pathological conditions through their interaction with some angiogenic factors. Our aim was to investigate the role of some angiogenesis-related ECM proteins in the remodeling heart. Methods: We examined cardiac tissue samples from 21 explanted human hearts and 10 non-failing hearts before transplantation. Each specimen was submitted to morphological and biomolecular analysis. Results: We demonstrated a reduced expression of α2-chain laminin mRNA in pathological samples that could play an important role in the progression of cardiac failure by contributing to sarcolemma modifications. Reduced expression of tenascin cytotactin (TN-C) and TN-X in explanted hearts indicated chronic cardiac damage and an impaired capacity to stimulate new vessel development. The observed type IV collagen increase was not related to neoangiogenesis, as reflected by the decreased expression of vascular endothelial growth factor (VEGF)-A and VEGF receptor-2. The inverse correlation between heart dimension and VEGF-A immunopositivity seems particularly interesting. Conclusions: Our findings suggest that ECM reacts strongly to ischemic damage in failing hearts through some important modifications of its protein composition. Nevertheless, this reaction cannot completely restore myocardium structure if it is not supported by adequate neoangiogenesis. The decrease in some ECM proteins related to vessel development has a negative effect on postischemic neoangiogenesis and clinical outcome.

Potential role of an athlete-focused echocardiogram in sports eligibility

Sudden cardiac death(SCD)of an athlete is a rare but tragic event and sport activity might play a trigger role in athletes with underlying structural or electrical heart diseases.Preparticipation screenings(PPs)have been conceived for the potential to prevent SCD in young athletes by early identification of cardiac diseases.The European Society of Cardiology protocol for PPs includes history collection,physical examination and baseline electrocardiogram,while further examinations are reserved to individuals with abnormalities at first-line evaluation.Nevertheless,transthoracic echocardiography has been hypothesized to have a primary role in the PPs.This review aims to describe how to approach an athlete-focused echocardiogram,highlighting what is crucial to focus on for the different diseases(cardiomyopathies,valvulopathies,congenital heart disease,myocarditis and pericarditis)and when is needed to pay attention to overlap diagnostic zone(“grey zone”)with the athlete's heart.Once properly tested,focused echocardiography by sports medicine physicians may become standard practice in larger screening practices,potentially available during first-line evaluation.

Evaluation of Xpert MTB/RIF Ultra for Diagnosis of Extrapulmonary Tuberculosis: A Retrospective Analysis in a Low-Tuberculosis Prevalence Setting

Background: Extrapulmonary tuberculosis (EPTB) remains difficult to diagnose because the clinical specimens to be examined are often paucibacillary and obtained with difficulty from inaccessible sites. An updated Xpert® MTB/RIF Ultra (Ultra) test has been designed and licensed to improve sensitivity in the detection of Mycobacterium tuberculosis complex. The aim of the present study is to evaluate the performance of Ultra assay for the clinical diagnosis of EPTB in a low tuberculosis prevalence country. Methods: A retrospective analysis was performed at “A. O dei Colli” of Naples on consecutive extrapulmonary specimens for EPTB across a three-year period. All different types of extrapulmonary specimens were tested for EPTB by smear microscopy, culture and Ultra assay in accordance with relevant guidelines. Results: A total of 606 EPTB samples, 561 culture negative EPTB and 45 culture positive EPTB were included. Using culture as reference standard, the overall sensitivities and specificities of Ultra assay were 95.6% (95% CI 84.8 - 99.5) and 97.5% (95% CI 95.8 - 98.6) respectively. Sensitivity and specificity of Ultra for individual category of specimens were also performed. Conclusion: In a low-tuberculosis prevalence setting, Ultra assay confirms to have a good performance in the diagnosis of EPTB for all different extrapulmonary samples.

Mallory-Weiss syndrome from giant gastric trichobezoar: A case report

BACKGROUND Mallory-Weiss syndrome(MWS),representing a linear mucosal laceration at the gastroesophageal junction,is a quite frequent cause of upper gastrointestinal bleeding,usually induced by habitual vomiting.The subsequent cardiac ulceration in this condition is likely due to the concomitance of increased intragastric pressure and inappropriate closure of the gastroesophageal sphincter,collectively inducing ischemic mucosal damage.Usually,MWS is associated with all vomiting conditions,but it has also been described as a complication of prolonged endoscopic procedures or ingested foreign bodies.CASE SUMMARY We described herein a case of upper gastrointestinal bleeding in a 16-year-old girl with MWS and chronic psychiatric distress,the latter of which deteriorated following her parents’divorce.The patient,who was residing on a small island during the coronavirus disease 2019 pandemic lockdown period,presented with a 2-mo history of habitual vomiting,hematemesis,and a slight depressive mood.Ultimately,a huge intragastric obstructive trichobezoar was detected and discovered to be due to a hidden habit of continuously eating her own hair;this habit had persisted for the past 5 years until a drastic reduction in food intake and corresponding weight loss occurred.The relative isolation in her living status without school attendance had worsened her compulsory habit.The hair agglomeration had reached such enormous dimensions and its firmness was so hard that its potential for endoscopic treatment was judged to be impossible.The patient underwent surgical intervention instead,which culminated in complete removal of the mass.CONCLUSION According to our knowledge,this is the first-ever described case of MWS due to an excessively large trichobezoar.

Depression and chronic heart failure in the elderly： an intriguing relationship

长期的心失败和压抑的混乱有高流行和发生在老。几研究显示出消沉怎么趋于加重共存的长期的心失败和它的临床的结果并且反过来也如此，在特别老。在长期的心失败和消沉在之间的否定协同老可以被接近仅仅考虑位于两个这些条件下面的 multifaceted pathophysiological 特征，例如行为因素， neurohormonal 激活，煽动性的调停人， hypercoagulability 和脉管的损坏。不过，在这二个条件之间的 pathophysiological 连接还很好没被建立。尽管有在长期的心失败的消沉的高流行老病人和它的否定预示的价值，因为分享的症状，它特别经常是未被认出的。用可靠问询表，屏蔽心情混乱因此与长期的心失败在老病人被推荐，就算不能由心理健康职业运动员代替诊断会见。在这个背景，消沉的治疗要求包括的一条多学科的途径：心理疗法，抗抑郁剂，锻练训练和 electroconvulsive 治疗。尽管有冲突结果，有选择血清素举起禁止者的药理学治疗改进生活的质量但是不保证更好的结果。锻练训练在改进生活和预后的质量是有效的，但是同时心脏的康复服务是极大地 underutilized。

Wilson's disease: Prospective developments towards new therapies

Wilson's disease(WD) is an autosomal recessive disorder of copper metabolism, caused by mutations in the ATP7 B gene. A clear demand for novel WD treatment strategies has emerged. Although therapies using zinc salts and copper chelators can effectively cure WD, these drugs exhibit limitations in a substantial pool of WD patients who develop intolerance and/or severe side effects. Several lines of research have indicated intriguing potential for novel strategies and targets for development of new therapies. Here, we review these new approaches, which comprise correction of ATP7 B mutants and discovery of new compounds that circumvent ATP7B-deficiency, as well as cell and gene therapies. We also discuss whether and when these new therapeutic strategies will be translated into clinical use, according to the key requirements for clinical trials that remain to be met. Finally, we discuss the hope for the current rapidly developing research on molecular mechanisms underlying WD pathogenesis and for the related potential therapeutic targets to provide a solid foundation for the next generation of WD therapies that may lead to an effective, tolerable and safe cure.

Gastrointestinal and liver infections in children undergoing antineoplastic chemotherapy in the years 2000

AIM: To review gastrointestinal and liver infections in children undergoing antineoplastic chemotherapy. To look at gut microflora features in oncology children.METHODS: We selected studies published after year 2000, excluding trials on transplanted pediatric patients. We searched English language publications in MEDLINE using the keywords: "gastrointestinal infection AND antineoplastic chemotherapy AND children", "gastrointestinal infection AND oncology AND children", "liver infection AND antineoplastic chemotherapy AND children", "liver abscess AND chemotherapy AND child", "neutropenic enterocolitis AND chemotherapy AND children", "thyphlitis AND chemotherapy AND children", "infectious diarrhea AND children AND oncology", "abdominal pain AND infection AND children AND oncology", "perianal sepsis AND children AND oncology", "colonic pseudo-obstruction A N D o n c o l o g y A N D c h i l d A N D c h e m o t h e r a p y ", "microflora AND children AND malignancy", "microbiota AND children AND malignancy", "fungal flora AND children AND malignancy". We also analysed evidence from several articles and book references.RESULTS: Gastrointestinal and liver infections represent a major cause of morbidity and mortality in children undergoing antineoplastic chemotherapy. Antineoplastic drugs cause immunosuppression in addition to direct toxicity, predisposing to infections, although the specific risk is variable according to disease and host features. Common pathogens potentially induce severe diseases whereas opportunistic microorganisms may attack vulnerable hosts. Clinical manifestations can be subtle and not specific. In addition, several conditions are rare and diagnostic process and treatments are not standardized. Diagnosis may be challenging, however early diagnosis is needed for quick and appropriate interventions. Interestingly, the source of infectionin those children can be exogenous or endogenous. Indeed, mucosal damage may allow the penetrance of endogenous microbes towards the bowel wall and their translocation into the bloodstream. However, only limited knowledge of intestinal dysbiosis in oncology children is available. CONCLUSION: The diagnostic work-up requires a multimodal approach and should be implemented(also by further studies on new biomarkers) for a prompt and individualized therapy.

Relationship between microvessel count and post-hepatectomy survival in patients with hepatocellular carcinoma

AIM: To elucidate the relationship between the microvessel count (MVC) by CD34 analyzed by immunohistochemical method and prognosis in hepatocellular carcinoma (HCC) patients who underwent hepatectomy based on our preliminary study. METHODS: We examined relationships between MVC and clinicopathological factors in 128 HCC patients. The modifi ed Japan Integrated Staging score (mJIS) was applied to examine subsets of HCC patients. RESULTS: Median MVC was 178/mm^2, which was used as a cut-off value. MVC was not signif icantly associated with any clinicopathologic factors or postoperative recurrent rate. Lower MVC was associated with poor disease-free and overall survivals by univariate analysis (P = 0.039 and P = 0.087, respectively) and lower MVC represented an independent poor prognostic factor in disease-free survival by Cox’s multivariateanalysis (risk ratio, 1.64; P = 0.024), in addition to tumor size, vascular invasion, macroscopic fi nding and hepatic dysfunction. Signifi cant differences in disease-free and overall survivals by MVC were observed in HCC patients with mJIS 2 (P = 0.046 and P = 0.0014, respectively), but not in those with other scores. CONCLUSION: Tumor MVC appears to offer a useful prognostic marker of HCC patient survival, particularly in HCC patients with mJIS 2.

Persistent hypertransaminasemia in asymptomatic children: A stepwise approach

We aimed to examine the major causes of isolated chronic hypertransaminasemia in asymptomatic children and develop a comprehensive diagnostic flow diagram. A MEDLINE search inclusive of publications throughout August 2012 was performed. We found only a small number of publications that had comprehensively investigated this topic. Consequently, it was difficult to construct a diagnostic flowchart similar to those already available for adults. In children, a "retesting panel" prescription, including gamma-glutamyl transpeptidase and creatine kinase in addition to aminotransferases, is considered a reasonable approach for proficiently confirming the persistence of the abnormality, ruling out cholestatic hepatopathies and myopathies, and guiding the subsequent diagnostic steps. If re-evaluation of physical and historical findings suggests specific etiologies, then these should be evaluated in the initial enzyme retesting panel. A simple multistep diagnostic algorithm incorporating a large number of possible pediatric scenarios, in addition to the few common to adults, is available. Accurately classifying a child with asymptomatic persistent hypertransaminas-emia may be a difficult task, but the results are critical for preventing the progression of an underlying, possibly occult, condition later in childhood or during transition. Given the high benefit/cost ratio of preventing hepatic deterioration, no effort should be spared in diagnosing and properly treating each case of persistent hypertransaminasemia in pediatric patients.