Successful treatment of acute liver failure due to Wilson’s disease: Serendipity or fortuity?

BACKGROUND Acute liver failure(ALF)may be the first and most dramatic presentation of Wilson’s disease(WD).ALF due to WD(WD-ALF)is difficult to distinguish from other causes of liver disease and is a clear indication for liver transplantation.There is no firm recommendation on specific and supportive medical treatment for this condition.AIM To critically evaluate the diagnostic and therapeutic management of WD-ALF patients in order to improve their survival with native liver.METHODS A retrospective analysis of patients with WD-ALF was conducted in two pediatric liver units from 2018 to 2023.RESULTS During the study period,16 children(9 males)received a diagnosis of WD and 2 of them presented with ALF.The first was successfully treated with an unconventional combination of low doses of D-penicillamine and zinc plus steroids,and survived without liver transplant.The second,exclusively treated with supportive therapy,needed a hepatotransplant to overcome ALF.CONCLUSION Successful treatment of 1 WD-ALF patient with low-dose D-penicillamine and zinc plus steroids may provide new perspectives for management of this condition,which is currently only treated with liver transplantation.

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.

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-11Rα in human intestinal adenocarcinomas, we examined 115 cases of surgically resected human colonic adenocarcinoma and 11 cases of adenoma by immunohistochemistry 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- 11Rα 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-11Rα proteins. CONCLUSION： IL-11 and IL-11Rα are highly expressed in human colorectal adenocarcinoma and the IL-11Rα expression is correlated with clinicopathological factors, These findings suggest that the expression of IL-11Rα is an important factor for the invasion of human colorectal adenocarcinoma.

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.

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 m.lIS 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.

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

Objective Doppler derived mitral peak early diastolic filling velocity to deceleration time ratio （E/DT） has been proposed as parameter for predicting prognosis in general population. This study prospectively investigates the incremental prognostic value of E/DT over clinical, conven- tional eehocardiographic and mitral-Doppler variables in patients hospitalized for decompensated heart failure （HF）. Methods We analyzed 95 HF patients （mean age 64.8 ± 12.2 years） hospitalized at our institution from January 2010 to March 2012. The primary end-point was cardiac death or hospitalization, whichever occurred first. Cox regression analysis was performed to identify significant predictors of outcomes. Results During follow-up （median 37.7 months） 13 patients died and 44 were hospitalized for a cardiac event. At univariable analysis, New York Heart Association （NYHA） functional class, furosemide dosage, lateral tricuspidal annular plane systolic excursion, deceleration lime and E/DT were predictive of outcome. At multivariable analysis, E/DT was the only predictor of prognosis （hazard ratio = 1.02, P = 0.018）, giving incremental prognostic information to clinical and other echocardio-graphic measures （global chi-square from 15.4 to 25.2; P = 0.032）. Conclusions FJDT gives independent and incremental prognostic information in HF patients.

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 etiol-ogy and the severity of the disease, while fewer studies have explored the potential capability of nuclear cardi-ology to guide cardiac resynchronization therapy （CRT） and to select patients for implantable cardioverter defbrillators （ICD）. Left ventricular synchrony may be assessed by radionuclide angiography or gated single-photon 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 posi-tron emission tomography and could improve conven-tional response prediction criteria for CRT. Preliminary data also exists on integrated positron emission tomog-raphy/computed tomography approach for assessing myocardial viability, identifying the location of biven-tricular pacemaker leads, and obtaining left ventricular functional data, including contractile phase analysis. Fi-nally, cardiac imaging with autonomic radiotracers may be useful in predicting CRT response and for identifying patients at risk for sudden cardiac death, therefore po-tentially 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 defne 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

To verify the precision and accuracy of transglutaminase antibodies (TGA) assays across Mediterranean countries. METHODSThis 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 IgA. Each sample was analysed three times on three different days, with each centre running a total of 21 tests. 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 (CoVar = σ/μ), the mean accuracy (Accur = Vobserved - Vreal) and the mean percent variation (Var% = [(Vobserved - Vreal)/Vreal] × 100). RESULTSThe 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. CONCLUSIONTGA 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.

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.

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

Chronic heart failure and depressive disorders have a high prevalence and incidence in the elderly. Several studies have shown how depression tends to exacerbate coexisting chronic heart failure and its clinical outcomes and vice versa, especially in the elderly. The negative synergism between chronic heart failure and depression in the elderly may be approached only taking into account the multifaceted pathophysiological characteristics underlying both these conditions, such as behavioural factors, neurohormonal activation, inflammatory mediators, hypercoagulability and vascular damage. Nevertheless, the pathophysiological link between these two conditions is not well established yet. Despite the high prevalence of depression in chronic heart failure elderly patients and its negative prognostic value, it is often unrecognized especially because of shared symptoms. So the screening of mood disorders, using reliable questionnaires, is recommended in elderly patients with chronic heart failure, even if cannot substitute a diagnostic interview by mental health professionals. In this setting, treatment of depression requires a multidisciplinary approach including： psychotherapy, antidepressants, exercise training and electroconvulsive therapy. Pharmacological therapy with selective serotonin reuptake inhibitors, despite conflicting results, improves quality of life but does not guarantee better outcomes. Exercise training is effective in improving quality of life and prognosis but at the same time cardiac rehabilitation services are vastly underutilized.