Non-neoplastic portal vein thrombosis in cirrhotic patients: prevalence and possible correlation with major liver function scores (CTP and MELD)

La trombosi portale non neoplastica (PVT) è una complicanza frequente della cirrosi epatica. Attualmente, gli unici fattori di rischio associati, ripetutamente confermati in letteratura, sono il precedente sanguinamento da varici esofagee e la piastrinopenia che sbilancia il precario equilibrio coagulativo tipico della cirrosi. Tra Gennaio 2013 e Ottobre 2015, sono stati arruolati prospetticamente 253 pazienti cirrotici (età media 58,8 ± 10,3 (23 – 75) anni) senza neoplasie anamnestiche e/o malattia ematologica e liberi da terapia anticoagulante/antiaggregante assunta er altre cause. Nel campione raccolto sono stati studiati: lo stadio di malattia secondo il Child-Pugh (CP) e il Model for end-stage liver disease (MELD) scores, eziologia, età ed esami laboratoristici. I pazienti con PVT sono stati il 13%, di cui il 63,3% maschi, significativamente più giovani dei controllonegativi (51,9 ± 13,2 (23 – 75) anni; P=0,004), con una maggior piastrinopenia (73,1 ± 48,1 (25 – 174); P = 0,001), INR > 1.25 in 54,5% dei casi (P=0,024) e MELD >10 in 86,2% (P=0,001). INR e MELD sono state considerate anche come valore continuo senza raggiungere la significatività come eziologia, ematocrito, Bilirubina ttale, AST, ALT, Albumina, Creatinina e CP score e classe. All'analisi multivariata solo la conta piastrinica è risultata indipendentemente associata alla presenza di PVT (OR = 0.97, 95% CI: 0.96-0.99; P <0.001) come da letteratura. Le trombocitopenie ereditarie (ITs) sono un gruppo eterogeneo di disordini genetici con diversi gradi di severità e cmplessità caratterizzate da piastrinopenia associata o meno a sanguinamento di variabile entità. Tali disordini, in un substrato così favorevole come la cirrosi epatica, potrebbe spiegare l'eterogeneità dei quadri clinici e la risposta apparentemente casuale alla terapia anticoagulante. Non abbiamo ancora dati che confermino questa ipotesi alternativa, ma se così fosse, probabilmente l'approccio clinico a questa problematica cambierebbe significativamente.Non-neoplastic porta vein thrombosis (PVT) in cirrhotic patients is a frequent complication of liver cirrhosis. Yet, only confirmed data about its natural history are the association with variceal bleeding and low platelet count which influences this precarious coagulation balance. In our prospective study, from January 2013 to October 2015, we enrolled 253 cirrhotic patients (mean age 58,8 ± 10,3 (23 – 75) years) without a history of malignancy and/or hematological disease and who aren’t on oral anticoagulants or antiplatelet therapy taken for other reasons. Overall were subsequently studied according to the degree of liver disease using the Child-Pugh (CP) and Model for end-stage liver disease (MELD) scores, etiology, age and blood tests. Patient with PVT, of which 63,3% males, was significantly younger (51,9 ± 13,2 (23 – 75) yrs; P=0,004), with lesser platelet count (73,1 ± 48,1 (25 – 174); P = 0,001), INR > 1.25 in 54,5% of cases (P=0,024) and MELD >10 in 86,2% (P=0,001). INR and MELD considered as continuous variables were not significant as well as etiology, hematocrit, total Bilirubin, AST, ALT, Albumine, Creatinine and CP score and class. In multivariate analysis, only the platelet count was independently associated with the occurance of PVT (OR = 0.97, 95% CI: 0.96-0.99; P <0.001) confirming the literature. The inheritated thrombocytopenias (ITs) are a heterogeneous group of genetic disorders with different degrees of complexity and severity, characterized by a low platelets count associated or not with a bleeding tendency which varies from absent to very strict. This group of diseases, in the context of an extremely favorable substrate such as cirrhotic degeneration, would explain the heterogeneity of the cadres and random responses to anticoagulation. We have no data yet certain about this, but if this hypothesis be confirmed, the clinical approach to the disease might change dramatically

A case of pneumonia and sepsis in cirrhosis as paradigm of the problems in the management of bacterial infections in cirrhosis and of the limitations of current knowledge

Bacterial infections are a major problem in the management of liver cirrhosis. They represent the first precipitating cause of death since patients with cirrhosis carry an increased risk of sepsis, sepsis-induced organ failure and death. Although the clinical presentation is often misleading, the presence of bacterial infection should always be actively searched and ruled out with certainty whenever a cirrhotic patient is admitted to the hospital with an acute clinical deterioration. Major changes in the epidemiology of bacterial infections have also occurred in the last decade making the choice of empirical antibiotic therapy a challenge. We report a paradigmatic case of a 54-year old man with hepatitis C-related cirrhosis admitted to the hospital for worsening of his ascites and onset of hepatic encephalopathy, an excellent example for the difficulties of management of sepsis in cirrhosis and the limits of current knowledge

Improved clinical investigation and evaluation of high-risk medical devices: the rationale and objectives of CORE-MD (Coordinating Research and Evidence for Medical Devices)

: In the European Union (EU) the delivery of health services is a national responsibility but there are concerted actions between member states to protect public health. Approval of pharmaceutical products is the responsibility of the European Medicines Agency, whereas authorizing the placing on the market of medical devices is decentralized to independent 'conformity assessment' organizations called notified bodies. The first legal basis for an EU system of evaluating medical devices and approving their market access was the medical device directives, from the 1990s. Uncertainties about clinical evidence requirements, among other reasons, led to the EU Medical Device Regulation (2017/745) that has applied since May 2021. It provides general principles for clinical investigations but few methodological details-which challenges responsible authorities to set appropriate balances between regulation and innovation, pre- and post-market studies, and clinical trials and real-world evidence. Scientific experts should advise on methods and standards for assessing and approving new high-risk devices, and safety, efficacy, and transparency of evidence should be paramount. The European Commission recently awarded a Horizon 2020 grant to a consortium led by the European Society of Cardiology and the European Federation of National Associations of Orthopaedics and Traumatology, that will review methodologies of clinical investigations, advise on study designs, and develop recommendations for aggregating clinical data from registries and other real-world sources. The CORE-MD project (Coordinating Research and Evidence for Medical Devices) will run until March 2024; here we describe how it may contribute to the development of regulatory science in Europe

Acute Liver Failure Caused by Amanita phalloides Poisoning

Mushroom poisoning is a relatively rare cause of acute liver failure (ALF). The present paper analyzes the pathogenesis, clinical features, prognostic indicators, and therapeutic strategies of ALF secondary to ingestion of Amanita phalloides, which represents the most common and deadly cause of mushroom poisoning. Liver damage from Amanita phalloides is related to the amanitins, powerful toxins that inhibit RNA polymerase II resulting in a deficient protein synthesis and cell necrosis. After an asymptomatic lag phase, the clinical picture is characterized by gastrointestinal symptoms, followed by the liver and kidney involvement. Amatoxin poisoning may progress into ALF and eventually death if liver transplantation is not performed. The mortality rate after Amanita phalloides poisoning ranges from 10 to 20%. The management of amatoxin poisoning consists of preliminary medical care, supportive measures, detoxification therapies, and orthotopic liver transplantation. The clinical efficacy of any modality of treatment is difficult to demonstrate since randomized, controlled clinical trials have not been reported. The use of extracorporeal liver assist devices as well as auxiliary liver transplantation may represent additional therapeutic options

Observational prospective study comparing mucoactive and antibiotic treament in the management of acute cough from upper respiratory tract infections

Since the efficacy of antibiotics in the management of cough from upper respiratory tract infections (URTI) is unclear, we conducted an observational study to evaluate the efficacy of antibiotic compared to symptomatic treatment in adults with productive cough from URTI in a real life setting

Liver Stiffness measurments using Fibroscan after three months of IFN-based antiviral therapy is unlikely to predict viral response in cirrhotic patients

Background and Aims: Chronic HCV infection (CHC) is the leading cause of mortality from liver cirrhosis and hepatocellular carcinoma. Antiviral therapy can prevent disease progression. Transient Elastografy (TE; Fibroscan) is an accurate surrogate marker to liver fibrosis, by measuring liver stiffness (LS). LS decrease has been associated with sustained virologic response (SVR). In this study we aimed to assess the changes of LS measurments in CHC patients during and one year after Interferon (IFN)-based antiviral therapy (IFN/ribavirin) or (telaprevir+IFN/ribavirin). Methods: This is an ongoing study, in which consecutive 69 CHC patients (53.6% females, mean age 57.9±11.4) who underwent antiviral therapy for at least 20 weeks were enrolled. LS was measured using Fibroscan at baseline, after three months, at the end of treatment and one year after treatment discontinuation. Fibrosis was graded using METAVIR score. Results: Twenty patients were treated with triple therapy and 49 with IFN/ribavirin. Fifty patients had SVR and 19 were non-responders. LS changed significantly in all patients and independently from the initial fibrosis stage, genotype, type of treatment, basal ALT and BMI. Twelve months after treatment discontinuation, we found that in SVR patients: F0–F1, F2 and F3 patients (39.1%, 7.2% and 17.4%; respectively) showed no significant LS decrease (P = 0.186, 0.068 and 0.075; respectively). Conversely, in F4 patients (36.2%) LS was significantly decreased (P = 0.015) after one year of treatment completion. In all patients with no SVR, no significant decrease in LS was observed. Interestingly, all Patients with F4 fibrosis (even non-responders) showed an initial significant decrease in LS (P = 0.024) at 3 months after the start of treatment. However, this decrease was not predictive of SVR; area under the ROC curve 0.369 (CI %: 0.145–0.592) P = 0.265. Conclusions: Performance of LS measurements for fibrosis assessment confirmed results from previous studies. Our preliminary data suggest that LS changes significantly in CHC patients treated with IFN-based antiviral therapy (standard and triple therapy with telaprevir) and it decreases significantly in responders with high initial LS measurements independently from the type treatment. Initial significant decrease in LS measurements in such patients is unlikely to predict an SVR

Transcatheter Embolization for Giant Splenic Artery Aneurisms: Still an Open Question

Transcatheter embolization is the mainstay of the therapy of splenic artery aneurysms (SAAs) in patients with portal hypertension. It is indicated when the SAA diameter reaches 20 mm. Although endovascular techniques are effective and safe for the treatment of medium-sized SAAs, little is known about their applicability to large-sized SAAs. Herein, we report a case of giant SAA, which was treated with transcatheter coil embolization. The case was not considered suitable for surgery because of the presence of severe portal hypertension. The procedure was complicated by bacterial infection of the coils within the aneurismatic sac, leading to the development of hepatic failure. A liver transplant was then successfully performed despite the presence of a nonresponsive infection

METODO E KIT PER LA DIAGNOSI DELLA SENSIBILITA’ AL GLUTINE NON ASSOCIATA ALLA CELIACHIA

La sensibilità al glutine non celiaca (dall’anglosassone, non-celiac gluten sensitivity, NCGS) è una condizione caratterizzata da sintomi intestinali ed extra-gastrointestinali, provocati dall’ingestione di glutine in assenza di una diagnosi certa di malattia celiaca. La NCGS interessa tra lo 0.6 ed il 6% della popolazione e non sono attualmente disponibili biomarcatori a fini diagnostici. Pertanto, la diagnosi viene ipotizzata, ma difficilmente provata con certezza, in base al miglioramento dei sintomi in seguito all’esclusione del glutine dalla dieta ed alla loro ricorrenza in seguito alla reintroduzione del glutine nella dieta. Uno dei problemi legati alla diagnosi della NCGS risiede nella difficoltà nel distinguerla, in base alla sintomatologia, dalla sindrome dell’intestino irritabile. La presente invenzione permette di diagnosticare la sensibilità al glutine non celiaca e di differenziarla da patologie intestinali funzionali quali la sindrome dell’intestino irritabile. L'invenzione si basa sul dosaggio di una proteina sierica, la zonulina, e sulla raccolta di dati clinici

Does additional antimicrobial treatment have a better effect on URTI cough resolution than homeopathic symptomatic therapy alone? A real-life preliminary observational study in a pediatric population

Abstract Background: The effectiveness of a homeopathic syrup on cough has been demonstrated in an adult population in a previous double-blind randomized study. The present prospective observational study investigated children affected by wet acute cough caused by non-complicated URTIs, comparing those who received the homeopathic syrup versus those treated with the homeopathic syrup plus antibiotic. Objectives: The aims were: 1) to assess whether the addition of antibiotics to a symptomatic treatment had a role in reducing the severity and duration of acute cough in a pediatric population, as well as in improving cough resolution; 2) to verify the safety of the two treatments. Methods: Eighty-five children were enrolled in an open study: 46 children received homeopathic syrup alone for 10 days and 39 children received homeopathic syrup for 10 days plus oral antibiotic treatment (amoxicillin/clavulanate, clarithromycin, and erythromycin) for 7 days. To assess cough severity we used a subjective verbal category-descriptive (VCD) scale. Results: Cough VCD score was significantly (P &lt; 0.001) reduced in both groups starting from the second day of treatment (-0.52 ± 0.66 in the homeopathic syrup group and -0.56 ± 0.55 in children receiving homeopathic syrup plus oral antibiotic treatment). No significant differences in cough severity or resolution were found between the two groups of children in any of the 28 days of the study. After the first week (day 8) cough was completely resolved in more than one-half of patients in both groups. Two children (4.3 %) reported adverse effects in the group treated with the homeopathic syrup alone, versus 9 children (23.1 %) in the group treated with the homeopathic syrup plus antibiotics (P = 0.020). Conclusions: Our data confirm that the homeopathic treatment in question has potential benefits for cough in children as well, and highlight the strong safety profile of this treatment. Additional antibiotic prescription was not associated with a greater cough reduction, and presented more adverse events than the homeopathic syrup alone

Liver Stiffness improvement in subjects with advanced chronic hepatitis C treated with direct antiviral agents

none9nononeGamal, N.; Conti, F.; Mastroroberto, M.; Scuteri, A.; Cursaro, C.; Guarneri, V.; Di Donato, R.; Vitale, G.; Andreone, P.Gamal, N.; Conti, F.; Mastroroberto, M.; Scuteri, A.; Cursaro, C.; Guarneri, V.; Di Donato, R.; Vitale, G.; Andreone, P