Search

Sarcopenia, defined as progressive and generalized loss of muscle mass and strength, is common in chronic liver disease. It significantly impacts the quality of life and increases the risk of liver-related complications and mortality in cirrhotic patients. Moreover, recent studies showed a negative impact of sarcopenia on patients awaiting liver transplantation (LT), on post-LT outcomes, and on response to hepatocellular carcinoma therapies. Data about the influence of sex on the incidence, prevalence, diagnosis and treatment of sarcopenia in chronic liver diseases are poor and conflicting. The aims of this review of the literature are to define sex differences in sarcopenic cirrhotic patients and to highlight the necessity of a sex stratified analysis in future studies. This analysis of the literature showed that most of the studies are retrospective, with a higher prevalence of sarcopenia in males, probably due to anatomical differences between the sexes. Moreover, diagnostic criteria for sarcopenia are different between studies, as there is not a defined cut-off and, as a consequence, no comparable results. In conclusion, sex seems to have an impact on sarcopenia, and future studies must accurately investigate its role in identifying and treating high-risk patients, reducing the negative impact of sarcopenia on the survival and quality of life of cirrhotic patients.

In patients with cirrhosis, particularly those with hepatocellular carcinoma (HCC), hypercoagulability may be associated with purported increased risks of portal vein thrombosis and cirrhosis progression. In this study, we extensively investigated hemostatic alterations potentially responsible for the thrombotic tendency in HCC, and evaluated whether such alterations were predictive of hepatic decompensation. Patients with cirrhosis at all stages were prospectively recruited and underwent an extensive hemostatic assessment, including all procoagulant factors and inhibitors, thrombin generation with and without thrombomodulin (TG), profibrinolytic and antifibrinolytic factors, and plasmin-antiplasmin complex. In study part 1 (case control), we compared alterations of coagulation and fibrinolysis in patients with cirrhosis with versus without HCC. In study part 2 (prospective), the subgroup of patients with decompensated cirrhosis was followed for development of further decompensation, and predictors of outcome were assessed by multivariate analysis. One-hundred patients were recruited (50 each with and without HCC). Severity of cirrhosis was comparable between groups. Median HCC volume was 9 cm3 (range: 5-16). Compared with controls, patients with HCC demonstrated a significantly more prothrombotic hemostatic profile due to increased TG and reduced activation of fibrinolysis, independent of cirrhosis stage. During a median follow-up of 175 days, 20 patients with decompensated cirrhosis developed further episodes of decompensation that were predicted by low FVII and high plasminogen activator inhibitor-1 levels, independent of Model for End-Stage Liver Disease score. Conclusion: Patients with cirrhosis with HCC have profound hyper-coagulable changes that can account for their increased thrombotic tendency. In contrast, hypercoagulability in patients with decompensated cirrhosis is more likely a consequence of chronic liver disease rather than a driver for cirrhosis progression.

Background Microvesicles (MVs) play a role in inflammation, coagulation, and vascular homeostasis in liver disease. Aim To characterize circulating plasma MVs profile in patients with decompensated cirrhosis and acute kidney injury (AKI). Methods We measured the levels of total, endothelial, platelet, tissue factor (TF)+, leukocyte and hepatocyte MVs by new generation flow-cytometry in a prospective cohort of patients with decompensated cirrhosis with and without AKI. Results Eighty patients with decompensated cirrhosis were recruited (40 each with and without AKI). Patients with cirrhosis with AKI had significantly higher calcein+ (total), endothelial, and platelet-MVs. Conversely, TF+, leukocyte, and hepatocyte-MVs were comparable between groups. Resolution of AKI was associated with significantly decreased total and endothelial-MVs that became comparable with those in patients without AKI. Platelet MVs significantly decreased but remained higher compared to patients without AKI. TF+MVs significantly decreased and became lower than patients without AKI. Leukocyte and hepatocyte-MVs remained unchanged. Creatinine (OR 4.3 [95%CI 1.8–10.7]), MELD (OR 1.13 [95%CI 1.02–1.27]), any bleeding (OR 9.07 [95%CI 2.02–40.6]), and hepatocyte-MVs (OR 1.04 [95%CI 1.02–1.07]) were independently associated with 30-day mortality. Conclusion AKI worsened vascular and cellular homeostasis in patients with cirrhosis, particularly by inducing endothelial dysfunction and platelet activation. AKI did not worsen systemic inflammation and hepatocytes activation.

Background: Direct-acting antivirals are highly effective for the treatment of hepatitis C virus (HCV) infection, regardless race/ethnicity. We aimed to evaluate demographic, virological and clinical data of HCV-infected migrants vs. natives consecutively enrolled in the PITER cohort. Methods: Migrants were defined by country of birth and nationality that was different from Italy. Mann-Whitney U test, Chi-squared test and multiple logistic regression were used. Results: Of 10,669 enrolled patients, 301 (2.8%) were migrants: median age 47 vs. 62 years, (p < 0.001), females 56.5% vs. 45.3%, (p < 0.001), HBsAg positivity 3.8% vs. 1.4%, (p < 0.05). Genotype 1b was prevalent in both groups, whereas genotype 4 was more prevalent in migrants (p < 0.05). Liver disease severity and sustained virologic response (SVR) were similar. A higher prevalence of comorbidities was reported for natives compared to migrants (p < 0.05). Liver disease progression cofactors (HBsAg, HIV coinfection, alcohol abuse, potential metabolic syndrome) were present in 39.1% and 47.1% (p > 0.05) of migrants and natives who eradicated HCV, respectively. Conclusion: Compared to natives, HCV-infected migrants in care have different demographics, HCV genotypes, viral coinfections and comorbidities and similar disease severity, SVR and cofactors for disease progression after HCV eradication. A periodic clinical assessment after HCV eradication in Italians and migrants with cofactors for disease progression is warranted.

ObjectiveThe benefit of direct-acting antivirals (DAAs) against HCV following successful treatment of hepatocellular carcinoma (HCC) remains controversial. This meta-analysis of individual patient data assessed HCC recurrence risk following DAA administration.DesignWe pooled the data of 977 consecutive patients from 21 studies of HCV-related cirrhosis and HCC, who achieved complete radiological response after surgical/locoregional treatments and received DAAs (DAA group). Recurrence or death risk was expressed as HCC recurrence or death per 100 person-years (100PY). Propensity score-matched patients from the ITA.LI.CA. cohort (n=328) served as DAA-unexposed controls (no-DAA group). Risk factors for HCC recurrence were identified using random-effects Poisson.ResultsRecurrence rate and death risk per 100PY in DAA-treated patients were 20 (95% CI 13.9 to 29.8, I2=74.6%) and 5.7 (2.5 to 15.3, I2=54.3), respectively. Predictive factors for recurrence were alpha-fetoprotein logarithm (relative risk (RR)=1.11, 95% CI 1.03 to 1.19; p=0.01, per 1 log of ng/mL), HCC recurrence history pre-DAA initiation (RR=1.11, 95% CI 1.07 to 1.16; pConclusionEffects of DAA exposure on HCC recurrence risk remain inconclusive. Active clinical and radiological follow-up of patients with HCC after HCV eradication with DAA is justified.

In patients with decompensated cirrhosis, procedure‐related bleeding is a potentially lethal complication. Routine coagulation tests such as international normalized ratio and platelet count do not predict bleeding risk. We investigated whether thromboelastography (TEG) can identify patients with cirrhosis who are at risk of procedure‐related bleeding. As a part of a prospective study on hemostasis in decompensated cirrhosis, patients had TEG performed on admission and were followed prospectively during hospitalization for the development of procedure‐related bleeding. Eighty patients with cirrhosis were included. Among the 72 who had procedures performed, 7 had procedure‐related bleeding, which was major in three cases (two following paracentesis and one following thoracentesis). Conventional coagulation tests were comparable between bleeding and nonbleeding patients, whereas TEG parameters of k‐time (4.5 minutes vs. 2.2 minutes; P = 0.02), α‐angle (34° vs. 59°; P = 0.003), and maximum amplitude (37 mm vs. 50 mm; P = 0.004) were significantly different (all indicative of hypocoagulability). TEG maximum amplitude (MA), a marker of overall clot stability, accurately discriminated between patients who had major, life‐threatening bleeding (all with MA 30 mm), whereas a platelet count

A silicon photonic circuit comprising all the building blocks necessary to demonstrate optical communication between two sockets interconnected through an Arrayed Waveguide Grating Router (AWGR) is reported. The article focuses on the robustness of the interconnection scheme to the unavoidable wavelength and thermal fluctuations observed in real datacenter environments. To improve the reliability of the system, a feedback control mechanism, based on contactless integrated photonic probes (CLIPP) and heater actuators, is added to the interconnection to monitor in parallel the working point of each sensitive device and keep it locked in real-time. Experimental results demonstrate successful operations in a 30 Gbit/s data routing scenario at $\text{5}\cdot \text{10}^{-11}$ bit error rate, irrespective of sudden wavelength shifts of up to 200 pm or of iterated thermal variations in a 10 $^\circ$ C temperature range, with a recovery time of around 30 ms. These results prove that AWGR-based interconnections equipped with real-time drift compensation systems can be a viable option in multi-socket layouts even in highly demanding environments.

Objective To evaluate the efficacy of visual inspection with acetic acid (VIA) screening combined with a cervical smear in Uganda. Methods Nine screening campaigns were held in Uganda between January 2011 and October 2019. In the last three campaigns, a new approach was used: the cervical smear was performed before the VIA test and, in case of a positive VIA test, the slide was sent for examination. The data collected were divided into two groups: the first six campaigns and the last three campaigns. Results During the study period, 10 520 women were screened, of whom 911 had a positive VIA test. The VIA test showed 84.2% false positives. In the first group, the VIA test was positive in 516 women, of whom 93% were referred for further examinations. In the second group, the VIA test was positive in 395 women, but the cervical smear was positive in only 65 women. Thus, only 16.5% women were referred for further examinations. Conclusion Combining cervical smear, VIA test, and slide analysis in positive VIA tests may allow women who need treatment to be selected more effectively, while waiting for other more expensive solutions to become more affordable for this setting.

Objectives We aimed to systematically describe the use of dexmedetomidine as a treatment regimen for prolonged sedation in children and perform a meta-analysis of its safety profile. Data sources PubMed, EMBASE, Cochrane Library, Scopus, Web of Science, ClinicalTrials.gov, and CINAHL were searched from inception to November 30, 2018. Study selection We included studies involving hospitalized critically ill patients less than or equal to 18 years old receiving dexmedetomidine for prolonged infusion (≥ 24 hr). Data extraction Data extraction included study characteristics, patient demographics, modality of dexmedetomidine use, associated analgesia and sedation details, comfort and withdrawal evaluation scales, withdrawal symptoms, and side effects. Data synthesis Literature search identified 32 studies, including a total of 3,267 patients. Most of the studies were monocentric (91%) and retrospective (88%); one was a randomized trial. Minimum and maximum infusion dosages varied from 0.1-0.5 µg/kg/hr to 0.3-2.5 µg/kg/hr, respectively. The mean/median duration range was 25-540 hours. The use of a loading bolus was reported in eight studies (25%) (range, 0.5-1 µg/kg), the mode of weaning in 11 (34%), and the weaning time in six of 11 (55%; range, 9-96 hr). The pooled prevalence of bradycardia was 2.6% (n = 10 studies; 14/387 patients; 95% CI, 0.3-7.3; I = 75%), the pooled prevalence incidence of bradycardia was 2.6% (n = 10 studies; 14/387 patients; 95% CI, 0.3-7.3; I = 75%), the pooled incidence of hypotension was 6.1% (n = 8 studies; 19/304 patients; 95% CI, 0.8-15.9; I = 84%). Three studies (9%) reported side effects' onset time which in all cases was within 12 hours of the infusion starting. Conclusions High-quality data on dexmedetomidine use for prolonged sedation and a consensus on correct dosing and weaning protocols in children are currently missing. Infusion of dexmedetomidine can be considered relatively safe in pediatrics even when longer than 24 hours.

A 63-year-old woman presented with a clinically malignant mass. Core biopsy showed features resembling endometriosis. The glands were GATA3 and oestrogen receptor positive consistent with mammary origin and had no myoepithelial layer. The excision also showed a fibroepithelial component with stromal overgrowth, frequent mitoses and invasive margin consistent with a malignant phyllodes tumour. KMT2D and SETD2 mutations were present in both the conventional phyllodes tumour and endometriosis-like areas and are also described in endometriosis raising interesting questions about these lesions. This unusual pattern is a potential diagnostic pitfall, so it is helpful to be aware of it.

The integration of human and artificial intelligence (AI) in medicine has only recently begun but it has already become obvious that intelligent systems can dramatically improve the management of liver diseases. Big data made it possible to envisage transformative developments of the use of AI for diagnosing, predicting prognosis and treating liver diseases, but there is still a lot of work to do. If we want to achieve the 21st century digital revolution, there is an urgent need for specific national and international rules, and to adhere to bioethical parameters when collecting data. Avoiding misleading results is essential for the effective use of AI. A crucial question is whether it is possible to sustain, technically and morally, the process of integration between man and machine. We present a systematic review on the applications of AI to hepatology, highlighting the current challenges and crucial issues related to the use of such technologies.

Key Points Question Are clinical guidelines for the early detection and diagnostic workup of child physical abuse complete, clear, and consistent across high-income countries? Findings In this systematic review that included 20 clinical guidelines issued in 15 countries, guidelines were clear but incomplete and discrepant, particularly in the definition of sentinel injuries and in recommendations for exploratory laboratory testing and advanced imaging. Meaning This systematic review found a lack of standardized guidelines for the identification and management of child physical abuse, which may contribute to practice variation., This systematic review evaluates the completeness, clarity, and consistency of guidelines from high-income countries for the detection and diagnosis of child physical abuse., Importance The highly variable practices observed regarding the early detection and diagnostic workup of suspected child physical abuse contribute to suboptimal care and could be partially related to discrepancies in clinical guidelines. Objective To systematically evaluate the completeness, clarity, and consistency of guidelines for child physical abuse in high-income countries. Evidence Review For this systematic review, national or regional guidelines that were disseminated from 2010 to 2020 related to the early detection and diagnostic workup of child physical abuse in infants aged 2 years or younger by academic societies or health agencies in high-income countries were retrieved. The definitions of sentinel injuries and the recommended diagnostic workup (imaging and laboratory tests) for child physical abuse were compared. Data were analyzed from July 2020 to February 2021. Findings Within the 20 included guidelines issued in 15 countries, 168 of 408 expected statements (41%) were missing and 10 statements (4%) were unclear. Among 16 guidelines characterizing sentinel injuries, all of them included skin injuries, such as bruises, hematoma, or burns, but only 8 guidelines (50%) included intraoral injuries and fractures. All 20 guidelines agreed on the indication for radiological skeletal survey, head computed tomography, and head magnetic resonance imaging but differed for those of bone scintigraphy, follow-up skeletal survey, spinal magnetic resonance imaging, cranial ultrasonography, chest computed tomography, and abdominal ultrasonography and computed tomography. Additionally, 16 guidelines agreed on exploring primary hemostasis and coagulation but not on the tests to perform, and 8 guidelines (50%) mentioned the need to investigate bone metabolism. Conclusions and Relevance These findings suggest that guidelines for the diagnosis of child physical abuse in infants were often clear but lacked completeness and were discrepant on major issues. These results may help identify priorities for well-designed original diagnostic accuracy studies, systematic reviews, or an international consensus process to produce clear and standardized guidelines to optimize practices and infant outcomes.

We report a case of a 76-year-old man presenting with a 12-month history of a solitary lesion on his scalp. The histopathology was consistent with a grade 2/3 osteosarcoma extending to the subcutis. Full-body imaging excluded any involvement of the underlying bony tissue or solid organ malignancy, thus a diagnosis of primary cutaneous osteosarcoma (PCO) was made. Given the exceedingly rare nature of PCO, we discuss the clinico-pathological features of this case and those previously reported in the literature.

Background Young children’s healthy development depends on nurturing care, which ensures health, nutrition, responsive caregiving, safety and security, and early learning. Infancy and childhood are characterized by rapid growth and development, and these two factors contribute largely to determining health status and well-being across the lifespan. Identification of modifiable risk factors and prognostic factors during the critical periods of life will contribute to the development of effective prevention and intervention strategies. The NASCITA (NAscere e creSCere in ITAlia) study was created to evaluate physical, cognitive, and psychological development, health status and health resource utilization during the first six years of life in a cohort of newborns, and to evaluate potential associated factors. Methods NASCITA is an ongoing, dynamic, prospective, population-based birth cohort study of an expected number of more than 5000 newborns who will be recruited in 22 national geographic clusters starting in 2019. It was designed to follow children from birth to school entry age for a wide range of determinants, disorders, and diseases. Recruitment of the newborns (and their parents) will take place during the first routine well-child visit, which takes place at the office of the pediatrician assigned to them by the local health unit of residence, and which is scheduled for all newborns born in Italy within the first 45 days of their life. Data will be web-based and collected by the family pediatricians during each of the 7 standard well-child visits scheduled for all children during their first 6 years of life. Information on every contact with the enrolled children in addition to these prescheduled visits will be also recorded. Discussion The NASCITA cohort study provides a framework in which children are followed from birth to six-years of age. NASCITA will broaden our understanding of the contribution of early-life factors to infant and child health and development. NASCITA provides opportunities to initiate new studies, also experimental ones, in parts of the cohort, and will contribute relevant information on determinants and health outcomes to policy and decision makers. Cohort details can be found on https://coortenascita.marionegri.it. Trial registration Clinicaltrials.gov: NCT03894566. Ethics committee approval: 6 February 2019, Verbale N 59.

A multichannel impedance-sensing CMOS chip for the readout of noninvasive light detectors in silicon photonics (SiP) is presented. The performance of the lock-in phase-sensitive demodulator is improved thanks to a capacitive feedback transimpedance amplifier (TIA) equipped with an active discharge network, able to keep a dc output offset lower than 3 mV for leakage currents up to 4 nA while injecting a noise lower than 40 fA/ $\sqrt {\mathrm{ Hz}}$ . The addition of a sensor capacitance compensation system at the input of the chip allows a 30-fold increase of the stimulation amplitude, enabling the tracking of sub-picoSiemens conductance variations on a baseline of few $\mu \text{S}$ , with a bandwidth of 70 Hz. The chip performance opens the way to multipoint monitoring of complex photonic systems, addressing the challenges posed by the growing complexity of these architectures.

Sustained virological response (SVR) after interferon-based therapy is associated with improvement of insulin resistance (IR) in HCV-infected patients. Few data are available in the direct-acting antivirals (DAAs) era, especially in cirrhotic patients. We prospectively evaluated the long-term effect of DAAs on IR. Patients treated with DAAs between May 2015 and December 2016 in 3 tertiary care centres were recruited. Patients with diabetes were excluded. Biochemical and virological data were collected at baseline, 12/24/48 weeks (W) after the end of therapy (EOT). Presence of IR was defined by a 'homeostasis model assessment index for IR' [HOMA-IR])> 2.5. Liver fibroscan was performed at baseline, at 24/48W after EOT. Hundred and thirty-eight patients were enrolled (mean age 58 years, M/F 85/53, GT1 61%, 68.8% cirrhotic). Sixty-eight patients (94/138) had IR. Patients with IR had significantly higher stiffness than patients without it (23 ± 12 vs 15 ± 8; P < .0001). SVR12 was achieved in 135 (98%) patients, and 124 (90%) patients reached the 48W post-EOT. At this time point, the percentage of patients with IR significantly decreased to 49% (P = 0,01). HOMA-IR was significantly lower than baseline (1.8 vs 3; P < .001), and this was related to a significant reduction of insulin level (11.7 ± 6.3 vs 16.4 ± 8.3). High BMI was associated with a significantly lower probability of achieving a non-IR status at 24W (P = .05) and 48W (P = .03).In conclusion, SVR following DAAs led to a significant reduction of IR, even in patients with cirrhosis. Nevertheless, IR can persist after the achievement of SVR, especially in patients with high BMI.

Urinary tract infections, the most common severe bacterial infections in young infants, may be associated with co-existing meningitis. There is no consensus on when to perform a lumbar puncture in these infants. Our aim was to quantify the frequency of co-existing bacterial meningitis in febrile young infants acutely assessed for presumed urinary tract infections. We systematically reviewed PubMed, EMBASE, and the Cochrane Library for studies including infants ≤ 3 months with suspected/confirmed urinary tract infections, who underwent a lumbar puncture. Two investigators independently reviewed articles for inclusion and extracted relevant data. Our outcomes were culture-confirmed meningitis and identification of low-/high-risk criteria of meningitis. Overall 20/2079 studies, including 4191 infants, met inclusion criteria. A total of 11 infants had bacterial meningitis (frequency between 0 and 2.1% across studies) and were mostly neonates. Of 253 infants meeting the low-risk criteria (well-appearing, age 21 days, procalcitonin ≤ 0.5 ng/ml, and C reactive protein ≤ 20 mg/L) none developed meningitis, but only 15 underwent lumbar puncture.Conclusion: Co-existing bacterial meningitis in febrile young infants with urinary tract infection is rare. In those meeting low-risk criteria, a lumbar puncture may not be indicated. A case by case assessment should be made in infants not meeting low-risk criteria.Trial registration: CRD42018105339 What is known: • When caring for febrile infants ≤ 3 months with urinary tract infections, clinicians may have uncertainty on whether to perform a lumbar puncture (LP) for possible co-existing meningitis What is new: • An up-to-date systematic review of 20 studies found the frequency of co-existing meningitis in this population to be between 0 and 2.1% • Despite limited data, an LP may not be indicated in infants meeting low-risk criteria (being well-appearing, age 21 days, procalcitonin ≤ 0.5 ng/ml, C reactive protein ≤ 20 mg/L). Ill-appearance and neonatal age appear to be significant risk factors of co-existing meningitis.

In 1845, George Budd published a brief report regarding three patients who developed an obstruction of the hepatic veins. The condition has never been reported before, and was related to sepsis and alcoholism. Fifty-three years later, Hans Chiari postulated that syphilis was causing the obstruction of the hepatic veins, and enriched the debate with clinical and pathological correlations. Following the hypothesis on the 'phlebitis obliterans', several authors proposed other pathophysiological explanations including congenital causes, chronic trauma and exogenous toxins. RG Parker, in 1959, first recognized the relationship between obstruction of hepatic veins and thrombophilic conditions such as polycythaemia vera, pregnancy and hormonal therapy. Based on that, anticoagulant treatment was attempted, but with unsatisfactory outcome. We need to wait until the mid 1980s to see a widespread adoption of anticoagulants, with a consequent improvement of patients' survival. The fear of haemorrhagic events in patients with liver disease discouraged this therapeutic approach, and other surgical interventions (mainly port-systemic shunts) were conceived, but with high morbidity and mortality. The first liver transplantation in 1976 and the first trans-jugular intra-hepatic porto-systemic shunt in 1993 represented two major cornerstones in the management of Budd-Chiari syndrome (BCS). Such progresses allowed modifying the treatment of BCS until the modern concept of stepwise therapy. The present review thoroughly reviews the major landmarks in the discovery, treatment and clinical management of patients with BCS.

Gastrointestinal bleeding is one of the most relevant causes of death in patients with cirrhosis and clinically significant portal hypertension, with gastroesophageal varices being the most frequent source of hemorrhage. Despite survival has improved thanks to the standardization on medical treatment aiming to decrease portal hypertension and prevent infections, mortality remains significant. In this review, our goal is to discuss the most recent advances in the management of esophageal variceal hemorrhage in cirrhosis with specific attention to the treatment algorithms involving the use of indirect measurement of portal pressure (HVPG) and transjugular intrahepatic portosystemic shunt (TIPS), which aim to further reduce mortality in high-risk patients after acute variceal hemorrhage and in the setting of secondary prophylaxis.

We present a novel design for a reconfigurable silicon microring resonator filter exploiting non-integer Vernier ratio to achieve FSR-free spectral response. Hitless tunability across the extended C+L band (1520 nm-1620 nm) is achieved by introducing controllable loss in the MRRs of the filter.

The increasing requirements in terms of bandwidth and power efficiency demanded by telecommunication, automotive and datacenter applications are pushing copper-based interconnections close to their intrinsic limits [1]. On the same line, the emerging trends on new rack-scale multi-socket computational units are putting pressure on chip-to-chip interconnections, calling for high speed and low-latency performance at a reduced energy and cost [2]. These technological requirements are making copper-based interconnects the bottleneck of high-performance systems, suggesting the use of point-to-point optical connectivity not only for long range communications but also at short or ultra-short distances [3]. With respect to other solid-state solutions, Silicon Photonics (SiP) seems to be the ideal candidate to answer to these needs, as it shares the same fabrication technologies of the microelectronic industry and is therefore expected to play a significant role in the field.

Hyper-functional platelets are being proposed as a potential therapeutic target in multiple cancers. Whether this can be considered in patients with cirrhosis and hepatocellular carcinoma (HCC) is unknown as their platelet function has not yet been investigated. We evaluated platelet function in cirrhosis patients with HCC. Patients with cirrhosis with and without HCC were prospectively recruited. Platelet aggregation, a marker of platelet function, was assessed by impedance aggregometry with adenosine diphosphate (ADP), arachidonic acid (ASPI), and thrombin (TRAP) stimulation. Plasmatic levels of Von Willebrand factor antigen (VWF) were also determined. One-hundred patients were recruited (50 cirrhotics with and 50 without HCC). Cirrhosis severity by Child class and platelet count were comparable between cirrhotics with and without HCC. Cirrhotics with HCC had higher ADP- (45 vs. 28, p &lt, 0.001), ASPI- (47 vs. 28, 0.001), and TRAP- (85 vs. 75, p = 0.01) induced platelet aggregation than cirrhotics without HCC, all indicative of platelet hyper-function. The relatively increased platelet aggregation in patients with HCC was confirmed after adjusting the analysis for platelet count/severity of thrombocytopenia. Levels of VWF were higher in patients with vs. without HCC (348 vs. 267, p = 0.006), particularly in compensated cirrhosis. In patients with cirrhosis, HCC is associated with increased platelet aggregation and higher VWF. The clinical implications of these findings deserve further investigation.

OBJECTIVE:\ud We estimated the cost consequence of Italian National Health System (NHS) investment in direct-acting antiviral (DAA) therapy according to hepatitis C virus (HCV) treatment access policies in Italy.\ud \ud METHODS:\ud A multistate, 20-year time horizon Markov model of HCV liver disease progression was developed. Fibrosis stage, age and genotype distributions were derived from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. The treatment efficacy, disease progression probabilities and direct costs in each health state were obtained from the literature. The break-even point in time (BPT) was defined as the period of time required for the cumulative costs saved to recover the Italian NHS investment in DAA treatment. Three different PITER enrolment periods, which covered the full DAA access evolution in Italy, were considered.\ud \ud RESULTS:\ud The disease stages of 2657 patients who consecutively underwent DAA therapy from January 2015 to December 2017 at 30 PITER clinical centres were standardized for 1000 patients. The investment in DAAs was considered to equal €25 million, €15 million, and €9 million in 2015, 2016, and 2017, respectively. For patients treated in 2015, the BPT was not achieved, because of the disease severity of the treated patients and high DAA prices. For 2016 and 2017, the estimated BPTs were 6.6 and 6.2 years, respectively. The total cost savings after 20 years were €50.13 and €55.50 million for 1000 patients treated in 2016 and 2017, respectively.\ud \ud CONCLUSIONS:\ud This study may be a useful tool for public decision makers to understand how HCV clinical and epidemiological profiles influence the economic burden of HCV.

Background The coronavirus disease 2019 (COVID-19) is currently rare in children and they seem to have a milder disease course and better prognosis than adults. However, SARS-Cov-2 pandemic has indirectly caused problems in pediatric medical assistance. In view of this we wanted to draw a picture of what happened during health emergency and analyze future prospects for restarting. Methods We involved the Italian pediatric scientific societies institutionally collected in the Italian Federation of Associations and Scientific Societies of the Pediatric Area (FIARPED); We sent a questionnaire to all scientific societies about the pediatric care activity during the COVID-19 emergency and future perspectives for the phase of post-containment. Results The analysis of the questionnaires showed significant decrease of:admission, outpatient visits and specialist consultancy activities during the COVID-19 emergency, primarily linked to the fear of infection. Instead it was increased the serious degree of diseases admitted. Most of scientific societies maintained the relationship with chronic patients through some form of telemedicine, reporting a strong positive opinion about this modality. Finally showed the need to give life a new approach for hospitalizations and outpatient visits through a greater use of telemedicine, educational programs on families and a more decisive role of family pediatricians. Conclusions Our study highlighted many aspects that can be improved in pediatric care. We think that It will be necessary a new shared strategy to improve the management and continuity of care for pediatric patients, primarily developing a network of collaboration between families, family pediatrician and hospitals and by enhancing the use of new methods of telecommunications.

Flexible optical networks require reconfigurable devices with operation on a wavelength range of several tens of nanometers, hitless tuneability (i.e. transparency to other channels during reconfiguration), and polarization independence. All these requirements have not been achieved yet in a single photonic integrated device and this is the reason why the potential of integrated photonics is still largely unexploited in the nodes of optical communication networks. Here we report on a fully-reconfigurable add-drop silicon photonic filter, which can be tuned well beyond the extended C-band (almost 100 nm) in a complete hitless (>35 dB channel isolation) and polarization transparent (1.2 dB polarization dependent loss) way. This achievement is the result of blended strategies applied to the design, calibration, tuning and control of the device. Transmission quality assessment on dual polarization 100 Gbit/s (QPSK) and 200 Gbit/s (16-QAM) signals demonstrates the suitability for dynamic bandwidth allocation in core networks, backhaul networks, intra- and inter-datacenter interconnects., Reconfigurable wavelength-selective devices are essential components of flexible optical networks. Here the authors show a silicon-photonic add-drop multiplexer meeting the strict requirements of telecom systems in terms of broadband operation range, hitless tunability and polarization transparency.

Summary Background Radical surgery via total mesorectal excision might not be the optimal first-line treatment for early-stage rectal cancer. An organ-preserving strategy with selective total mesorectal excision could reduce the adverse effects of treatment without substantially compromising oncological outcomes. We investigated the feasibility of recruiting patients to a randomised trial comparing an organ-preserving strategy with total mesorectal excision. Methods TREC was a randomised, open-label feasibility study done at 21 tertiary referral centres in the UK. Eligible participants were aged 18 years or older with rectal adenocarcinoma, staged T2 or lower, with a maximum diameter of 30 mm or less; patients with lymph node involvement or metastases were excluded. Patients were randomly allocated (1:1) by use of a computer-based randomisation service to undergo organ preservation with short-course radiotherapy followed by transanal endoscopic microsurgery after 8–10 weeks, or total mesorectal excision. Where the transanal endoscopic microsurgery specimen showed histopathological features associated with an increased risk of local recurrence, patients were considered for planned early conversion to total mesorectal excision. A non-randomised prospective registry captured patients for whom randomisation was considered inappropriate, because of a strong clinical indication for one treatment group. The primary endpoint was cumulative randomisation at 12, 18, and 24 months. Secondary outcomes evaluated safety, efficacy, and health-related quality of life assessed with the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C30 and CR29 in the intention-to-treat population. This trial is registered with the ISRCTN Registry, ISRCTN14422743. Findings Between Feb 22, 2012, and Dec 19, 2014, 55 patients were randomly assigned at 15 sites; 27 to organ preservation and 28 to radical surgery. Cumulatively, 18 patients had been randomly assigned at 12 months, 31 at 18 months, and 39 at 24 months. No patients died within 30 days of initial treatment, but one patient randomly assigned to organ preservation died within 6 months following conversion to total mesorectal excision with anastomotic leakage. Eight (30%) of 27 patients randomly assigned to organ preservation were converted to total mesorectal excision. Serious adverse events were reported in four (15%) of 27 patients randomly assigned to organ preservation versus 11 (39%) of 28 randomly assigned to total mesorectal excision (p=0·04, χ2 test). Serious adverse events associated with organ preservation were most commonly due to rectal bleeding or pain following transanal endoscopic microsurgery (reported in three cases). Radical total mesorectal excision was associated with medical and surgical complications including anastomotic leakage (two patients), kidney injury (two patients), cardiac arrest (one patient), and pneumonia (two patients). Histopathological features that would be considered to be associated with increased risk of tumour recurrence if observed after transanal endoscopic microsurgery alone were present in 16 (59%) of 27 patients randomly assigned to organ preservation, versus 24 (86%) of 28 randomly assigned to total mesorectal excision (p=0·03, χ2 test). Eight (30%) of 27 patients assigned to organ preservation achieved a complete response to radiotherapy. Patients who were randomly assigned to organ preservation showed improvements in patient-reported bowel toxicities and quality of life and function scores in multiple items compared to those who were randomly assigned to total mesorectal excision, which were sustained over 36 months’ follow-up. The non-randomised registry comprised 61 patients who underwent organ preservation and seven who underwent radical surgery. Non-randomised patients who underwent organ preservation were older than randomised patients and more likely to have life-limiting comorbidities. Serious adverse events occurred in ten (16%) of 61 non-randomised patients who underwent organ preservation versus one (14%) of seven who underwent total mesorectal excision. 24 (39%) of 61 non-randomised patients who underwent organ preservation had high-risk histopathological features, while 25 (41%) of 61 achieved a complete response. Overall, organ preservation was achieved in 19 (70%) of 27 randomised patients and 56 (92%) of 61 non-randomised patients. Interpretation Short-course radiotherapy followed by transanal endoscopic microsurgery achieves high levels of organ preservation, with relatively low morbidity and indications of improved quality of life. These data support the use of organ preservation for patients considered unsuitable for primary total mesorectal excision due to the short-term risks associated with this surgery, and support further evaluation of short-course radiotherapy to achieve organ preservation in patients considered fit for total mesorectal excision. Larger randomised studies, such as the ongoing STAR-TREC study, are needed to more precisely determine oncological outcomes following different organ preservation treatment schedules. Funding Cancer Research UK.

With long-term survival after liver transplantation becoming the rule, care for medical problems arising over time in liver transplanted patients gained increasing importance. The most common causes of death occurring more than one year after liver transplantation are unrelated to liver diseases and facilitated by immunosuppressive treatments, such as malignancies, renal failure, cardiovascular, metabolic and infectious diseases. Recipients receive life-long follow-up care at transplant centers; however, the increasing number of liver transplanted patients is saturating the health care supply that transplant centers have to offer. Primary care physicians are increasingly exposed to liver transplanted patients even in the early periods after transplant and an understating of the most common risks and complications faced by these patients would enhance their care. This article reviews the long-term care of liver transplant recipients, emphasizing the key internal medicine-related issues that should be known by the primary care physicians. A specific section is devoted to implementing strategies to involve these physicians in the long-term follow-up of liver transplanted patients in close collaboration with transplant hepatologists.

Hepatitis B virus (HBV) is a major health problem worldwide, with approximatively 240 million people living with a chronic HBV infection. HBV chronic infection remains the major cause of hepatocellular carcinoma worldwide, with more than half of HCC patients being chronic HBV carriers, even if underlying mechanisms of tumorigenesis are not totally understood. HBV-related HCC can be prevented by reducing the exposure to HBV by vaccination or by treatment of CHB infection. Current treatment of CHB are Peg-IFN alpha and oral NUCs. Treating HBV infection, either with IFN or NUCs, substantially reduces the risk of HCC development, even if antiviral therapy fails to completely eliminate HCC risk. Among treated patients, cirrhosis, HBeAg negative at baseline and failure to remain in virological remission were associated with an increased risk of HCC. The reduction of the risk of developing HCC during antiviral therapy is largely dependent upon the maintenance of virological remission, since viral load is found to be the most important factor leading to cirrhosis and its complications, including liver cancer development. The question whether Peg-IFN-alpha is superior to NUCs and whether there is a superior agent among NUCs is still controversial. Several studies demonstrated that antiviral therapy with NUCs could reduce the risk of HCC recurrence after curative treatment of HBV-related HCC.

Malnutrition and sarcopenia have a high prevalence in cirrhotic patients. Frailty generally overlaps with malnutrition and sarcopenia in cirrhosis, leading to increased morbidity and mortality. Rapid nutritional screening assessment should be performed in all patients with cirrhosis, and more specific tests for sarcopenia should be performed in those at high risk. The pathogenesis of malnutrition in cirrhosis is complex and multifactorial and it is not just due to reduction in protein and calorie intake. Nutritional management in malnourished patients with cirrhosis should be undertaken by a multidisciplinary team to achieve adequate protein/calorie intake. While the role of branched-chained amino acids remains somewhat contentious in achieving a global benefit of decreasing mortality- and liver-related events, these latter and vitamin supplements, are recommended for those with advanced liver disease. Novel strategies to reverse sarcopenia such as hormone supplementation, long-term ammonia-lowering agents and myostatin antagonists, are currently under investigation. Malnutrition, sarcopenia and frailty are unique, inter-related and multidimensional problems in cirrhosis which require special attention, prompt assessment and appropriate management as they significantly impact morbidity and mortality.

The noise power spectral density of a detector is essential for determining the frequency of operation and readout architecture that yields an optimal signal-to-noise ratio. In this work, we characterize a waveguide-integrated PbTe mid-infrared detector and report on its noise spectrum, highlighting the presence of a current-dependent 1/f term dominating at low frequency and/or high bias over the Johnson component typical of a photoconductor. This behaviour, together with the substantially flat frequency response in the range between 1 kHz to 1 MHz, guide towards a lock-in readout strategy, that allows one to operate in the region of minimum noise without penalties in the detection performance. Practical guidelines to optimize the readout resolution are provided and the limit of detection of a gas sensing system exploiting PbTe photoconductors is derived, as an example of how a careful co-design of sensors and electronics can dramatically improve the detection performance.

Background & Aims Understanding factors responsible for the increased bleeding tendency in acute‐on‐chronic liver failure (ACLF) would improve the management of these complications. We investigated coagulation alterations in ACLF and assessed whether they were predictive of bleeding. Methods Cirrhosis patients with ACLF (cases) and acute decompensation (AD, controls) were prospectively recruited and underwent an extensive haemostatic assessment including standard tests, pro and anticoagulant factors, thrombomodulin‐modified thrombin generation (TG) and thromboelastometry (ROTEM®). In study part 1 (case‐control), we compared coagulation in ACLF vs AD. In study part 2 (prospective), all patients were followed for bleeding, and predictors of outcome were assessed. Results Ninety‐one patients were included (51 with ACLF, 40 with AD). Infections and ascites/renal dysfunction were the most common precipitating and decompensating events. Platelet count was lower while INR and activated partial thrombin time were longer in ACLF cohort vs AD. Regarding clotting factors, fibrinogen and factor VIII were comparable between groups while protein C and antithrombin were significantly reduced in ACLF. Endogenous thrombin potential by TG was comparable between groups. Clotting formation time and clot stability by ROTEM® were significantly lower in ACLF, indicative of a more hypocoagulable state. No haemostasis alteration could discriminate between patients who had bleeding complications during hospitalization and those who did not. Conclusion We found coagulation changes in ACLF to largely overlap with that of AD and evidence of preserved coagulation capacity in both groups. ROTEM alterations were indicative of a more pronounced hypocoagulable state in ACLF; however, no correlation was found between such alterations and bleeding.

INTRODUCTION Gastric antral vascular ectasia is a significant cause of gastrointestinal bleeding in patients with cirrhosis. AIM To assess safety/efficacy and cost/advantages of radiofrequency ablation for the treatment of gastric antral vascular ectasia in patients with cirrhosis. MATERIALS AND METHODS Patients with cirrhosis and severe gastric antral vascular ectasia who underwent radiofrequency ablation were enrolled. Clinical data, gastric antral vascular ectasia grade, and gastric antral vascular ectasia-related hospitalizations were collected. Primary outcome was defined as the absence of transfusion over the 6 months after radiofrequency. An economic analysis was performed in the same period. RESULTS Forty patients (50% Child B) were enrolled (80% refractory to argon plasma coagulation). Gastric antral vascular ectasia eradication was obtained in all patients and 65% of these patients achieved primary outcome. After radiofrequency, mean number of red blood cells transfusions dropped (from 25 to 0.9, P < 0.0001), with a parallel increase in hemoglobin (from 8 to 10.5 g/dL, P < 0.0001). No major complication occurred and liver function remained stable in all patients. The cost-analysis demonstrated a profound reduction of health care cost (from € 536.084 to € 189.044 in the 6 months before vs. after radiofrequency, respectively). These results were confirmed in the subgroup analysis in patients refractory to argon plasma coagulation. CONCLUSIONS Radiofrequency ablation is safe and effective for the treatment of gastric antral vascular ectasia in patients with cirrhosis, including those refractory to argon plasma coagulation. Although the cost of single radiofrequency ablation is relatively high, the cost-analysis demonstrated considerable saving.

Patients with hepatocellular carcinoma (HCC) are at high risk of second primary malignancies. As HCC has become the leading indication of liver transplant (LT), the aim of this study was to investigate whether the presence of HCC before LT could influence the onset of de novo malignancies (DNM). A cohort study was conducted on 2653 LT recipients. Hazard ratios (HR) of DNM development for patients transplanted for HCC (HCC patients) were compared with those of patients without any previous malignancy (non-HCC patients). All models were adjusted for sex, age, calendar year at transplant, and liver disease etiology. Throughout 17 903 person-years, 6.6% of HCC patients and 7.4% of non-HCC patients developed DNM (202 cases). The median time from LT to first DNM diagnosis was shorter for solid tumors in HCC patients (2.7 vs 4.5 years for HCC and non-HCC patients, respectively, P

The architecture of a low‐leakage switch in complementary metal‐oxide‐semiconductor (CMOS) technology developed to implement long‐term analogue memories for low‐power applications is presented. The switch reduces the leakage current using a cascade of modified pass‐transistors without active circuits, thus producing a negligible power consumption. The technique is simple, modular, robust, and reduces the leakage current down to tens of aA at room temperature using a TSMC 0.18 µm technology.

Background and Aims Risk stratification after cure from hepatitis C virus (HCV) infection remains a clinical challenge. We investigated the predictive value of noninvasive surrogates of portal hypertension (liver stiffness measurement [LSM] by vibration‐controlled transient elastography and von Willebrand factor/platelet count ratio [VITRO]) for development of hepatic decompensation and hepatocellular carcinoma in patients with pretreatment advanced chronic liver disease (ACLD) who achieved HCV cure. Approach and Results A total of 276 patients with pretreatment ACLD and information on pretreatment and posttreatment follow‐up (FU)‐LSM and FU‐VITRO were followed for a median of 36.6 months after the end of interferon‐free therapy. FU‐LSM (area under the receiver operating characteristic curve [AUROC]: 0.875 [95% confidence interval [CI]: 0.796‐0.954]) and FU‐VITRO (AUROC: 0.925 [95% CI: 0.874‐0.977]) showed an excellent predictive performance for hepatic decompensation. Both parameters provided incremental information and were significantly associated with hepatic decompensation in adjusted models. A previously proposed combined approach (FU‐LSM 25.3 kPa and/or FU‐VITRO > 3.3; 25.0% of patients), the risk of hepatic decompensation at 3 years following treatment was high (17.4%). Patients within the diagnostic gray‐zone for FU‐CSPH (17.8% of patients) had a very low risk of hepatic decompensation during FU (2.6%). The prognostic value of this algorithm was validated in an internal (n = 86) and external (n = 162) cohort. Conclusion FU‐LSM/FU‐VITRO are strongly and independently predictive of posttreatment hepatic decompensation in HCV‐induced ACLD. An algorithm combining these noninvasive markers not only rules in or rules out FU‐CSPH, but also identifies populations at negligible versus high risk for hepatic decompensation. FU‐LSM/FU‐VITRO are readily accessible and enable risk stratification after sustained virological response, and thus facilitate personalized management.

Many optoelectronic devices embedded in a silicon photonic chip, like photodetectors, modulators, and attenuators, rely on waveguide doping for their operation. However, the doping level of a waveguide is not always reflecting in an equal amount of free carriers available for conduction because of the charges and trap energy states inevitably present at the S i / S i O 2 interface. In a silicon-on-insulator technology with 10 15 c m − 3 p -doped native waveguides, this can lead to a complete depletion of the core from free carriers and to a consequently very high electrical resistance. This Letter experimentally quantifies this effect and shows how the amount of free carriers in a waveguide can be modified and restored to the original doping value with a proper control of the chip substrate potential. A similar capability is also demonstrated by means of a specific metal gate integrated above the waveguide that allows fine control of the conductance with high locality level. This paper highlights the linearity achievable in the conductance modulation that can be exploited in a number of possible applications.

Drug induced liver injury (DILI) is a necro-inflammatory liver disease caused by several drugs commonly used in clinical practice, herbs and dietary supplements prescribed for medical purposes. Despite its rarity, it represents the major cause of acute liver failure (ALF) requiring liver transplantation in USA and its frequency is increasing in Europe too. Two types of drug induced liver injury have been recognized: intrinsic and idiosyncratic. Predisposing factors may be classified in environmental, drugs- and individual- related risk factors, with the latter further distinguished in genetics and non-genetics. The liver injury can present with a hepatocellular, cholestatic or mixed pattern of disease. A definitive diagnosis of DILI is, nowadays, one of the main challenging issue in the management of these patients. Diagnosis often is based on suspicion derived from clinical history, biochemical exams and eventually on histological examination from liver biopsy. Score system may be helpful in these setting and new markers are gaining more prominence. Evaluation for liver transplantation is indicated when spontaneous resolution does not occur or in cases of ALF. Overall, the 1-year survival rate following liver transplantation is lower than that seen in patients who have been transplanted for chronic liver failure; however long-term survival is higher compared to other indications.

Hepatocellular carcinoma (HCC) represents the sixth most commonly diagnosed cancer and the fourth leading cause of cancer-related death worldwide. HCC occurs predominantly in patients with underlying chronic liver disease and cirrhosis, and it presents a poor prognosis in advanced stage. Since its approval, for the following 10 years, sorafenib remained the only systemic agent with proven clinical efficacy for patients with advanced HCC. Recently, more drugs have been studied and several advances in first‑line and second‑line treatment options should yield significant improvements in survival. Lenvatinib, another tyrosine‑kinase inhibitor, was found to be non-inferior to sorafenib in terms of overall survival (OS), with significantly better progression-free survival and objective response rate (ORR). The tyrosinekinase inhibitors, regorafenib and cabozantinib, were shown to significantly improve survival in the second‑line setting after sorafenib failure. Ramucirumab, a VEGF inhibitor, can also improve survival in the second‑line setting among patients with AFP≥400 ng/dL. Moreover, good efficacy was seen in phase I/II trials of immune checkpoint inhibitors as monotherapy. Ongoing trials are evaluating combination immune checkpoint inhibitor and tyrosine‑kinase inhibitors or VEGF inhibitors for increasing overall survival in this patient population with advanced HCC.

Background Portal vein thrombosis is the most common thrombotic complication in cirrhosis. About 60% of anticoagulated patients can achieve recanalization. Despite fondaparinux (FPX) theoretical advantages, data are lacking about safety and efficacy for treatment of portal vein thrombosis in cirrhosis. Methods Cirrhotic patients with portal vein thrombosis treated with FPX or low-molecular-weight heparin (LMWH) were retrospectively included. The extension of thrombosis at baseline and its evolution during anticoagulant treatment were evaluated. Patients were treated with LMWH or FPX at therapeutic dosage and reduction was considered in selected cases. Results There were 124 patients included. Main portal vein branch, splenic, and superior mesenteric veins were involved in 84%, 13%, and 36% of cases, respectively. Forty-one patients (33%) were treated with FPX and 83 (67%) with LMWH. The probability of resolution of thrombosis at 36 months was significantly higher in patients treated with FPX than in those treated with LMWH (77% vs 51%; P = .001), particularly when prescribed at reduced dose. With multivariate analysis, the treatment with FPX (hazard ratio 2.38; P = .002) and use of a full dose (hazard ratio 1.78; P = .035) were independent predictors of portal vein full recanalization. Bleeding rate was higher in patients treated with FPX than in those treated with LMWH (27% vs 13%; P = .06). Conclusions FPX appears to be more effective than LMWH in the treatment of portal vein thrombosis when used at reduced dose, also in complete thrombosis. FPX should be considered among possible treatments for portal vein thrombosis in cirrhosis.

Background Portal vein thrombosis (PVT) is the most common thrombotic complication in cirrhosis; however, local risk factors involved in its pathogenesis are still not fully investigated. The aim of the study was to evaluate hemostasis and endothelial damage in the portal vein in patients with cirrhosis and portal hypertension.Methods Adult cirrhotics undergoing transjugular intrahepatic portosystemic shunt were consecutively enrolled. Rotational thromboelastometry (ROTEM), dosage of total circulating glycosaminoglycans (GAGs), and endotoxemia levels (lipopolysaccharide [LPS]), along with evaluation of endothelial dysfunction by quantification of circulating endothelial microparticles (MPs), were performed on citrated peripheric and portal venous blood samples from each enrolled patient.Results Forty-five cirrhotics were enrolled. ROTEM analysis revealed the presence of a significant heparin-like effect in portal blood (median ɑ angle NATEM 50° vs. HEPTEM 55°, p = 0.027; median coagulation time NATEM 665 s vs. HEPTEM 585 s, p = 0.006), which was not detected in peripheral blood, and was associated with a higher concentration of circulating GAGs. Even though total annexin V-MP circulating MPs were less concentrated in the splanchnic district, the proportion of MPs of endothelial origin, with respect to annexin V-MP, was significantly increased in the portal district (p = 0.036). LPS concentration was higher in portal (197 pg/mL) compared with peripheral blood (165 pg/mL) (p Conclusion Evidences of a damage of glycocalyx along with increased concentration of endothelial MPs suggest the presence of a significant endothelial alteration in the portal vein with respect to peripheral veins. Portal site-specific endothelial damage could hamper its antithrombotic properties and may represent an important local risk factor in the pathogenesis of PVT.

Background & Aims The long-term impact of sustained virological response (SVR) after direct-acting antivirals (DAAs) on the hypercoagulability associated with HCV cirrhosis is unknown. We longitudinally evaluated the effect of DAAs treatment on cirrhotic coagulopathy. Methods Results Pro- and anticoagulant factor levels and thrombin generation were assessed in patients with HCV-related cirrhosis at baseline, end of therapy (EOT), at 12, 24 and 48 weeks (W) after EOT. Fifty-eight patients were enrolled (86% Child's A). SVR was 100%. Median factor VIII activity significantly decreased at EOT, 12 weeks and 24 weeks compared with baseline, whereas protein C significantly increased at 24 weeks and 48 weeks. Cirrhotic patients showed a slight but sustained increase in endogenous thrombin potential (ETP) with a statistically significant difference at EOT, 12 weeks, 24 weeks and 48 weeks compared with baseline. Conversely, thrombomodulin-modified ETP was elevated before treatment and decreased over time to normal levels at 24 weeks and 48 weeks. The ETP ratio decreased slowly at EOT and 12 weeks, and was significantly decreased at 24 weeks and 48 weeks compared with baseline (P

Bacterial infection (BI) is a common cause of impairment of liver function in patients with cirrhosis, especially in the liver transplant candidates. These patients share an immunocompromised state and increased susceptibility to develop community and hospital-acquired infections. The changing epidemiology of BI, with an increase of multidrug resistant strains, especially in healthcare-associated settings, represents a critical issue both in the waiting list and in the post-operative management. This review focused on the role played by BI in patients awaiting liver transplantation, evaluating the risk of drop-out from the waiting list, the possibility to undergo liver transplantation after recovery from infection or during a controlled infection.

Background & aims Survival rates after liver transplantation (LT) in paediatric recipients have significantly improved over time. However, data regarding outcomes after transition from Paediatric to Adult Healthcare Service (AHS) are still lacking. Therefore, we aimed to prospectively evaluate the outcome of LT recipients after transition, to access patients' non-adherence and identify potential risk factors for non-adherence. Methods All consecutive adolescent LT recipients moving to the AHS at Padua University Hospital were evaluated between 2010 and 2015. Demographic data, liver function tests, incidence of acute or chronic rejection episodes and adherence to medical prescription, were prospectively evaluated. An educational pilot study was implemented since 2015 to foster adherence during transition. Results In all, 32 patients (M/F 16/16, median age: 23 years) were evaluated. Median interval time between LT and transition was 15 years (range: 1-26 years). The main indication for LT was biliary atresia (31%), whereas immunosuppression regimen was tacrolimus-based in 75%. After a median follow-up of 29 months (range: 12-83), no significant modifications of liver function tests were observed. Biopsy-proven chronic rejection was diagnosed in 6/32 (18%) of patients, who had higher standard deviation of tacrolimus trough level than patients without (1.5 vs 1, P = .03). Non-adherence was reported in 8/32 (25%) of patients and was significantly associated with alcohol consumption (P = .003). Patient and graft survival were 96% and 93%, respectively. Conclusions Adolescent LT patients who undergo transition to the AHS have good long-term outcomes. However, a multidisciplinary approach aiming at fostering adherence should be used.