Liver-related aspects of valoctocogene roxaparvovec gene therapy for hemophilia A: expert guidance for clinical practice.

Adeno-associated virus (AAV)-based gene therapy (valoctocogene roxaparvovec) is an attractive treatment for hemophilia A. Careful clinical management is required to minimize the risk of hepatotoxicity, including assessment of baseline liver condition to determine treatment eligibility and monitoring liver function after gene therapy. This article describes recommendations (developed by a group of hemophilia experts) on hepatic function monitoring before and after gene therapy. To prevent harmful liver-related effects, gene therapy is contraindicated in patients with uncontrolled liver infections, autoimmune hepatitis, liver stiffness ≥8 kPa or cirrhosis. Before using gene therapy in patients with liver steatosis or other liver disorders, the risk of liver damage should be considered using a highly individualized approach. Treatment is not recommended in patients with abnormal liver enzymes, including alanine aminotransferase (ALT) at any level above the upper limit of normal (ULN). Therefore, pre-treatment assessment of liver health should include laboratory tests, abdominal ultrasound and liver stiffness measurements by transient elastography (TE). In the first year after therapy, ALT levels should be monitored 1-2 times/week to detect elevations ≥1.5 × ULN, which may require immunosuppressant therapy. Patients with ALT elevation should receive prednisone 60 mg/day for 2 weeks, followed by stepwise tapering when ALT returns to baseline. ALT monitoring should continue long-term (every 3-6 months), along with abdominal ultrasound (every 6 months) and TE (yearly) evaluations. When patients with good liver health are selected for treatment and closely monitored thereafter, ALT elevations can be promptly treated and are expected to resolve without long-term hepatic sequelae.

Dexamethasone and N-acetylcysteine before transarterial chemoembolization in hepatocellular carcinoma: A Western perspective.

Post-embolization syndrome (PES) is the most common complication in patients with hepatocellular carcinoma treated with transarterial chemoembolization. Many strategies have been evaluated to reduce the incidence of PES, but no standard prevention guidelines currently exist. In a single-center, placebo-controlled trial, Simasingha et al evaluated the prophylactic administration of a combination of dexamethasone and N-acetylcysteine and documented a significant reduction in the incidence of PES (from 80% to 6%), of post-procedural liver decompensation (from 14% to 0%), and a shorter hospital stay (4 days vs 6 days), alongside an acceptable safety profile. The results of this study raise several controversial points regarding their applicability in the Western world. In the West, there is a greater and increasing prevalence of metabolic and alcoholic etiologies of liver cirrhosis, so a not negligible number of patients with type II diabetes or hypertension would be excluded from high-dosage dexamethasone prophylaxis. Furthermore, in the West, there is a preferred use of drug-eluting beads loaded with doxorubicin, which are associated with a lower incidence of PES. A study on prophylaxis with dexamethasone and/or N-acetylcysteine in a Western population is hopefully awaited.

The Mediating Role of Insomnia Severity in the Relationship Between Anxiety Symptoms and Suicidal Ideation: A Real-World Study in a Psychiatric Inpatient Setting.

ABSTRACT: Insomnia and anxiety symptoms are independent clinical variables involved in suicidal ideation in psychiatric inpatients. In this article, we investigated the relationship among insomnia severity, severity of anxiety symptoms, and suicidal ideation in a sample of psychiatric inpatients with severe mental disorders. We used a mediation model considering insomnia severity as the possible mediator of the relationship between anxiety severity and suicidal ideation. We administered the Columbia Suicide Severity Rating Scale, the Insomnia Severity Index, and the Hamilton Anxiety Rating Scale to 116 consecutive inpatients to the psychiatric unit of Sant'Andrea Hospital in Rome. The effect of anxiety symptoms was mediated by insomnia severity; patients who perceive higher anxiety symptoms were more likely to experience higher levels of insomnia and, thus, higher suicidal ideation intensity. Results showed the importance of assessing and treating both insomnia and anxiety in clinical practice.

Genetic determinants of coping, resilience and self-esteem in schizophrenia suggest a primary role for social factors and hippocampal neurogenesis.

Schizophrenia is a severe psychiatric disorder, associated with a reduction in life expectancy of 15-20 years. Available treatments are at least partially effective in most affected individuals, and personal resources such as resilience (successful adaptation despite adversity) and coping abilities (strategies used to deal with stressful or threatening situations), are important determinants of disease outcomes and long-term sustained recovery. Published findings support the existence of a genetic background underlying resilience and coping, with variable heritability estimates. However, genome-wide analyses concerning the genetic determinants of these personal resources, especially in the context of schizophrenia, are lacking. Here, we performed a genome-wide association study coupled with accessory analyses to investigate potential genetic determinants of resilience, coping and self-esteem in 490 schizophrenia patients. Results revealed a complex genetic background partly overlapping with that of neuroticism, worry and schizophrenia itself and support the importance of social aspects in shapingthese psychological constructs. Hippocampal neurogenesis and lipid metabolism appear to be potentially relevant biological underpinnings, and specific miRNAs such as miR-124 and miR-137 may warrant further studies as potential biomarkers. In conclusion, this study represents an important first step in the identification of genetic and biological correlates shaping resilience, coping resources and self-esteem in schizophrenia.

The influence of PER3 VNTR genotypes on the age of onset in a group of bipolar I disorder patients: an exploratory study.

BACKGROUND: PER3 is a circadian gene that contains a variable number of tandem repeats (VNTR) which codifies for three genotypes: 4/4; 4/5; and 5/5 and is involved in non-visual response to light, a critical process associated with bipolar disorder onset. Benedetti et al. (Neurosci Lett 445(2):184-7) related this VNTR with bipolar disorder age of onset and linked genotype 5/5 with an earlier onset. In this study, we aimed to investigate these associations of PER3 VNTR genotypes with age of onset in a homogenous sample of German patients with bipolar I disorder through Kaplan-Meier curves. METHODS: 45 patients were enrolled and divided into three groups according to PER3 VNTR genotypes. Recognizing common biological features, we built a combined group of -5 allele carriers (4/5 + 5/5). As a primary outcome, Kaplan-Meier analysis was conducted to delineate the three genotypes' influence on age of onset. The secondary Kaplan-Meier analysis aimed to evaluate the relation between the 4/4 homozygotes group and the combined group (4/5 + 5/5) with age of onset. Finally, we proceeded to compare groups through a Log Rank Test and performed an analysis of covariance (ANCOVA). RESULTS: The Kaplan-Meier analysis with three separate genotypes didn't replicate the findings of Benedetti's study. The analysis comparing genotype 4/4 with the combined group showed the influence of PER3 VNTR variants on the age of onset and relates genotype 4/4 to an earlier onset. ANCOVA between the combined and the 4/4 genotype groups, correlated genotype 4/4 with an increased number of depressive episodes. CONCLUSION: This study showed no significant effect of PER3 VNTR genotypes on the age of onset and in linking genotype 5/5 with an earlier onset age. Contrasting results may arise from intrinsic differences between the two studies but also shed light on hypothetically different levels of functioning of PER3 VNTR genotypes in the context of bipolar pathology. Further studies will require bigger and more homogeneous clinical samples.

Serum-free light chains as a dependable biomarker for stratifying patients with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND AND AIMS: Adaptive immunity is gaining a significant role in progression of metabolic dysfunction-associated steatotic liver disease (MASLD). B-cell activity can be assessed by serum-free light chains (sFLCs) k and λ levels. The objective of the present investigation is to examine the utility of sFLCs as non-invasive biomarkers for the stratification of MASLD. METHODS: We enrolled a consecutive cohort from an outpatient liver unit. Diagnosis of metabolic dysfunction-associated steatohepatitis (MASH) was made with liver biopsy according to current guidelines. Compensated advanced chronic liver disease (cACLD) and clinically significant portal hypertension (CSPH) were defined according to Baveno VII criteria. sFLCs were measured by turbidimetry using an immunoassay. RESULTS: We evaluated 254 patients, 162/254 (63.8%) were male. Median age was 54 years old, and the median body mass index was 28.4 kg/m2. A total of 157/254 (61.8%) subjects underwent liver biopsy: 88 had histological diagnosis of MASH, 89 were considered as simple metabolic dysfunction-associated steatotic liver (MASL) and 77/254 (30.3%) patients with compensated metabolic dysfunction-associated cirrhosis. By using Baveno VII criteria, 101/254 (39.7%) patients had cACLD; among them, 45/101 (44.5%) had CSPH. Patients with cACLD showed higher sFLC levels compared with patients without cACLD (p < .01), and patients with CSPH showed higher sFLC levels than patients without CSPH (p < .01). At multivariable analysis, sFLCs were associated with cACLD (p < .05) independently from γ-globulins and other known dysmetabolic risk factors. κFLC was associated with CSPH (p < .05) independently from γ-globulins and other known dysmetabolic risk factors. CONCLUSION: sFLCs could be a simple biomarker for stratification of cACLD in MASLD patients.

Final Results from the First European Real-World Experience on Lusutrombopag Treatment in Cirrhotic Patients with Severe Thrombocytopenia: Insights from the REAl-World Lusutrombopag Treatment in ITalY Study.

Background and aims: Management of severe thrombocytopenia poses significant challenges in patients with chronic liver disease. Here, we aimed to evaluate the first real-world European post-marketing cohort of cirrhotic patients treated with lusutrombopag, a thrombopoietin receptor agonist, verifying the efficacy and safety of the drug. Methods: In the REAl-world Lusutrombopag treatment in ITalY (REALITY) study, we collected data from consecutive cirrhotic patients treated with lusutrombopag in 19 Italian hepatology centers, mostly joined to the "Club Epatologi Ospedalieri" (CLEO). Primary and secondary efficacy endpoints were the ability of lusutrombopag to avoid platelet transfusions and to raise the platelet count to ≥50,000/µL, respectively. Treatment-associated adverse events were also collected. Results: A total of 66 patients and 73 cycles of treatment were included in the study, since 5 patients received multiple doses of lusutrombopag over time for different invasive procedures. Fourteen patients (19%) had a history of portal vein thrombosis (PVT). Lusutrombopag determined a significant increase in platelet count [from 37,000 (33,000-44,000/µL) to 58,000 (49,000-82,000), p < 0.001]. The primary endpoint was met in 84% of patients and the secondary endpoint in 74% of patients. Baseline platelet count was the only independent factor associated with response in multivariate logistic regression analysis (OR for any 1000 uL of 1.13, CI95% 1.04-1.26, p 0.01), with a good discrimination power (AUROC: 0.78). Notably, a baseline platelet count ≤ 29,000/µL was identified as the threshold for identifying patients unlikely to respond to the drug (sensitivity of 91%). Finally, de novo PVT was observed in four patients (5%), none of whom had undergone repeated treatment, and no other safety or hemorrhagic events were recorded in the entire population analyzed. Conclusions: In this first European real-world series, lusutrombopag demonstrated efficacy and safety consistent with the results of registrational studies. According to our results, patients with baseline platelet counts ≤29,000/µL are unlikely to respond to the drug.

Frequency of and reasons behind non-listing in adult patients referred for liver transplantation: Results from a retrospective study.

BACKGROUND: Few studies have evaluated the frequency of and the reasons behind the refusal of listing liver transplantation candidates. AIM: To assess the ineligibility rate for liver transplantation and its motivations. METHODS: A single-center retrospective study was conducted on adult patients which entailed a formal multidisciplinary assessment for liver transplantation eligibility. The predictors for listing were evaluated using multivariable logistic regression. RESULTS: In our center, 314 patients underwent multidisciplinary work-up before liver transplantation enlisting over a three-year period. The most frequent reasons for transplant evaluation were decompensated cirrhosis (51.6%) and hepatocellular carcinoma (35.7%). The non-listing rate was 53.8% and the transplant rate was 34.4% for the whole cohort. Two hundred and five motivations for ineligibility were collected. The most common contraindications were psychological (9.3%), cardiovascular (6.8%), and surgical (5.9%). Inappropriate or premature referral accounted for 76 (37.1%) cases. On multivariable analysis, a referral from another hospital (OR: 2.113; 95%CI: 1.259-3.548) served as an independent predictor of non-listing. CONCLUSION: A non-listing decision occurred in half of our cohort and was based on an inappropriate or premature referral in one case out of three. The referral from another hospital was taken as a strong predictor of non-listing.

Rethinking the role of trazodone in the different depressive dimensions.

INTRODUCTION: The efficacy of trazodone for several psychopathologic dimensions of depression has been shown in the literature. Trazodone has been widely used in some clinical contexts (e.g. for insomnia and depression in the elderly). However, the role of trazodone in several aspects of depression is not well known. AREA COVERED: Eight experts from academic and medical centers across Italy met to identify the difficulties and barriers faced in daily clinical practice in the assessment and management of major depressive disorder and how the use of trazodone could address some unmet needs. The objective of the expert meetings and the present document was to increase knowledge of particular areas of treatment with trazodone. EXPERT OPINION: Evidence of the role of trazodone in patients affected by major depressive disorder with anxiety symptoms, insomnia, agitation, cognitive deficits, alcohol use disorders, physical comorbidities, and suicide risk has been identified, showing the effectiveness of trazodone in different presentations of major depressive disorder. The main characteristics of patients with depression for whom trazodone seems to be most effective have been identified, providing clinicians with information on possible uses of this drug in such population of patients.

Reduction of the Risk of Hepatocellular Carcinoma over Time Using Direct-Acting Antivirals: A Propensity Score Analysis of a Real-Life Cohort (PITER HCV).

The treatment of hepatitis C virus (HCV) with direct-acting antivirals (DAA) leads to high sustained virological response (SVR) rates, but hepatocellular carcinoma (HCC) risk persists in people with advanced liver disease even after SVR. We weighted the HCC risk in people with cirrhosis achieving HCV eradication through DAA treatment and compared it with untreated participants in the multicenter prospective Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. Propensity matching with inverse probability weighting was used to compare DAA-treated and untreated HCV-infected participants with liver cirrhosis. Kaplan-Meier analysis and competing risk regression analysis were performed. Within the first 36 months, 30 de novo HCC cases occurred in the untreated group (n = 307), with a weighted incidence rate of 0.34% (95%CI: 0.23-0.52%), compared to 63 cases among SVR patients (n = 1111), with an incidence rate of 0.20% (95%CI: 0.16-0.26%). The 12-, 24-, and 36-month HCC weighted cumulative incidence rates were 6.7%, 8.4%, and 10.0% in untreated cases and 2.3%, 4.5%, and 7.0% in the SVR group. Considering death or liver transplantation as competing events, the untreated group showed a 64% higher risk of HCC incidence compared to SVR patients (SubHR 1.64, 95%CI: 1.02-2.62). Other variables independently associated with the HCC occurrence were male sex, increasing age, current alcohol use, HCV genotype 3, platelet count ≤ 120,000/µL, and albumin ≤ 3.5 g/dL. In real-life practice, the high efficacy of DAA in achieving SVR is translated into high effectiveness in reducing the HCC incidence risk.

The clinical utility and relevance in clinical practice of DSM-5 specifiers for major depressive disorder: A Delphi expert consensus study.

Major depressive disorder (MDD) is a heterogeneous syndrome, associated with different levels of severity and impairment on the personal functioning for each patient. Classification systems in psychiatry, including ICD-11 and DSM-5, are used by clinicians in order to simplify the complexity of clinical manifestations. In particular, the DSM-5 introduced specifiers, subtypes, severity ratings, and cross-cutting symptom assessments allowing clinicians to better describe the specific clinical features of each patient. However, the use of DSM-5 specifiers for major depressive disorder in ordinary clinical practice is quite heterogeneous. The present study, using a Delphi method, aims to evaluate the consensus of a representative group of expert psychiatrists on a series of statements regarding the clinical utility and relevance of DSM-5 specifiers for major depressive disorder in ordinary clinical practice. Experts reached an almost perfect agreement on statements related to the use and clinical utility of DSM-5 specifiers in ordinary clinical practice. In particular, a complete consensus was found regarding the clinical utility for ordinary clinical practice of using DSM-5 specifiers. The use of specifiers is considered a first step toward a "dimensional" approach to the diagnosis of mental disorders.

Are visual analogue scales valid instruments to measure psychological pain in psychiatric patients?

OBJECTIVE: The Psychological-Physical-Pain Visual Analogue Scale (PPP-VAS) was thought to probably help in identifying patients at risk of suicide. However, no data on its validity to measure psychological pain was available. Our main aim was to investigate the convergent validity of the PPP-VAS using two well-validated scales of psychological pain, the Orbach and Mikulincer Mental Pain scale (OMMP) and the Holden et al. Psychache Scale. METHODS: This multicentre study recruited a total of 1618 adult psychiatric inpatients and outpatients in Italy. Psychological pain was evaluated using the OMMP, Holden et al., and PPP-VAS scales. Psychiatric status, suicidal status, physical pain, depression, and hopelessness were also assessed. RESULTS: A structural equation model (SEM) using the items of psychological pain from the PPP-VAS showed that items loaded significantly on the psychological pain factor and showed good fit. Similarly, a second SEM model using the three scales of psychological pain showed acceptable fit and converged into a psychological pain construct. Correlations between the PPP-VAS and depression, hopelessness, and physical pain showed moderate correlations (r = 0.43 to r = 0.67). Finally, psychological pain evaluated with the PPP-VAS was significantly related with recent suicidal ideation in all patients (OR [95 % CI] = 1.07 [1.05, 1.09]) and recent suicide attempts in moderately to severely depressed patients, OR [95 % CI] = 1.01 [1.02, 1.03]. CONCLUSION: The PPP-VAS showed good psychometric properties in evaluating psychological pain. The characteristics of the PPP-VAS makes this scale a great option for its use in clinical practice to detect patients at risk of suicide.

The relationship between obsessive-compulsive symptoms and real-life functioning in schizophrenia: New insights from the multicenter study of the Italian Network for Research on Psychoses.

BACKGROUND: Although obsessive-compulsive disorder (OCD) is highly prevalent in schizophrenia, its relationship with patients' real-life functioning is still controversial. METHODS: The present study aims at investigating the prevalence of OCD in a large cohort of non-preselected schizophrenia patients living in the community and verifying the relationship of OCD, as well as of other psychopathological symptoms, with real-life functioning along a continuum of OCD severity and after controlling for demographic variables. RESULTS: A sample of 327 outpatients with schizophrenia was enrolled in the study and collapsed into three subgroups according to OCD severity (subclinical, mild-moderate, severe). A series of structural equation modeling (SEM) was performed to analyze in each subgroup the association of obsessive-compulsive symptoms with real-life functioning, assessed through the Specific Levels of Functioning Scale and the UCSD Performance-Based Skills Assessment. Moreover, latent profile analysis (LPA) was performed to infer latent subpopulations. In the subclinical OCD group, obsessive-compulsive symptoms (OCS) were not associated with functioning, whereas in the mild-moderate OCD group, they showed a positive relationship, particularly in the domains of work and everyday life skills. The paucity of patients with severe OCD did not allow performing SEM analysis in this group. Finally, LPA confirmed a subgroup with mild-moderate OCS and more preserved levels of functioning. CONCLUSIONS: These findings hint at a positive association between mild-moderate OCD and real-life functioning in individuals with schizophrenia and encourage a careful assessment of OCD in personalized programs to sustain daily life activities.

Prognostic value of liver stiffness in patients hospitalized for acute decompensated heart failure: a meta-analysis.

PURPOSE: Heart failure (HF) is a major health problem affecting millions of people worldwide. In the latest years, many efforts have been made to identify predictors of poor prognosis in these patients. The aim of this systematic review and meta-analysis was to enlighten the correlation between liver stiffness (LS), assessed by Shear Wave Elastography techniques, and HF, particularly focusing on the prognostic value of LS on cardiovascular outcomes. METHODS: We searched the PUBMED databases (up to May 1st, 2023) for studies that enlightened the correlation between LS and cardiovascular outcomes in patients hospitalized for acute decompensated heart failure (ADHF). We performed a meta-analysis to estimate the efficacy of LS in predicting the prognosis of patients with ADHF. RESULTS: We analyzed data from 7 studies, comprising 677 patients, that assessed the prognostic value of LS in predicting cardiovascular outcomes in patients hospitalized for ADHF. The pooled analysis showed that increased liver stiffness was associated with higher risk of adverse cardiac events (hazard ratio 1.07 [1.03, 1.12], 95% CI). CONCLUSION: Increased LS is associated with poor prognosis in patients hospitalized for HF and might help effectively identify those patients at high risk for worse outcomes.

The Role of Lurasidone in Managing Depressive Symptoms in People with Schizophrenia: A Review.

BACKGROUND: Schizophrenia is a severe mental disorder characterized by positive, negative, affective, and cognitive symptoms. Affective symptoms in patients with schizophrenia have traditionally been overlooked or even neglected because they are not considered as fundamental as positive and negative symptoms in the choice of medication. METHODS: This paper aims to systematically evaluate the efficacy and safety of lurasidone in the treatment of depressive symptoms of schizophrenia. RESULTS: Lurasidone appears to be particularly effective on the depressive symptomatology of schizophrenia while also alleviating the positive and negative symptoms associated with the illness. CONCLUSIONS: The efficacy of lurasidone in treating patients with first-episode psychosis who present with predominant depressive symptoms suggests that this medication may be a valuable treatment option not only for established cases of schizophrenia but also for individuals in the early stages of the illness. The good tolerability of lurasidone is an important factor that may positively influence treatment decisions.

Global trends in youth suicide from 1990 to 2020: an analysis of data from the WHO mortality database.

Background: Suicide is a serious but preventable public health concern at the global level, showing relevant geographical differences. This study aims to monitor global temporal and geographical patterns in suicide mortality in pre-adolescents, adolescents, and young adults (i.e., aged 10-24 years), from 1990 to 2020 or the most recent available year. Methods: Using the World Health Organisation mortality database, we conducted an analysis on a subset of 52 countries with valid and high-quality data. We computed age-standardised suicide rates (ASR) by sex, country, and calendar year, and performed a joinpoint regression analysis to identify significant changes in the temporal suicide trends over the studied period. Findings: High variability in suicide rates and trends was observed, with a male-to-female ratio of two to five. Between 1990 and 2020, most European countries reported declining suicide trends, with some exceptions. In particular, alarming trends emerged in the United Kingdom, with annual rises of 2.5% (95% CI: 1.6-3.5) since 2005 among males and 8.5% (95% CI: 4.7-12.6) since 2012 among females. The most favorable trends and lowest suicide rates were in Southern Europe, with 3.1/100,000 persons in Italy (2020) and 3.5/100,000 persons in Spain (2021) among males, and 0.9/100,000 persons in Italy (2020) and 1.1/100,000 persons in Romania (2019) among females. Conversely, the highest rates were in Central-Eastern Europe, with 10.2/100,000 males in the Russian Federation (2019) and 10.0/100,000 males in Poland (2002). Higher suicide rates and significant increases were reported in not European areas. The highest ASR was 15.5/100,000 males in the United States of America, with an annual increase of 3.8% (95% CI: 3.1-4.5) among males in 2009-2020 and 6.7% (95% CI: 5.6-7.8) among females in 2007-2017, followed by a levelling off. Interpretation: Temporal and geographical comparisons of suicide mortality should be interpreted with caution due to potential misclassification or under-reporting of suicide deaths in some countries. Funding: None.

Hug sign in intraprocedural cone-beam-CT to predict short-term response to combined treatment of hepatocellular carcinoma.

OBJECTIVES: Combined treatment of ablation and chemoembolization for hepatocellular carcinoma represents a promising therapy to increase treatment efficacy and improve patient survival. The "hug sign" is a recently introduced radiological sign consisting in deposition of beads/contrast agent during transarterial chemoembolization in the hyperemic area surrounding the post-ablation volume, seen during intraprocedural unenhanced cone-beam CT, that may indicate intraprocedural success. Aim of our retrospective study was to analyze the usefulness of the "hug sign" at the intraprocedural unenhanced cone-beam CT as an early predictor of response to combined treatment, based on the hug sign angle. MATERIALS AND METHODS: Between January 2017 and September 2021 all patients with hepatocellular carcinoma which underwent a combined treatment of thermal ablation followed by chemoembolization were enrolled. All treated patients underwent immediate post-procedural unenhanced cone-beam CT to evaluate the deposition of contrast agent, lipiodol or radiopaque beads and to assess the percentage of coverage of the ablated area with the contrast agent (hug sign angle). Patients with missing pre-procedural, intra-procedural and/or post-procedural data/imaging, or with poor-quality post-procedural cone-beam CT images were excluded. RESULTS: 128 patients (mean age, 69.3 years ± 1.1 [standard deviation]; 87 men) were evaluated. Our study evidenced that 84.4% (81/85) of patients with a hug sign angle of 360° had no residual tumor at the first 1-/3-months follow-up examination. A hug sign angle of 360° also showed to be an independent protective factor against residual tumor at multivariate analysis. CONCLUSION: Unenhanced cone-beam CT performed at the end of a combined treatment with ablation plus chemoembolization can effectively predict an early treatment response on radiological images, when a hug sign angle of 360° was detected.

Suicide After Partner's Death in the Elderly Population: Results From a Nationwide Cohort Study in Italy.

OBJECTIVE: This study aims to investigate the effect of partner loss on suicide mortality for surviving partners in the elderly Italian population and to explore differences according to sex and time elapsed since the loss. DESIGN: This was a historical cohort study. SETTING: All Italian residents registered by the 15th Italian Population Census (9 October 2011) were linked to emigration records and death certificates for 2012-2017 to track migration, vital status, and cause of death. PARTICIPANTS: 5,068,414 individuals living as a couple, as registered in the census, and aged ≥69 years on January 1, 2012. MEASUREMENTS: Mortality rate ratios (MRR) estimated through Poisson regression models were used to compare suicide mortality at age ≥75 years between subjects who experienced partner loss and those who did not. RESULTS: Among people who experienced partner loss, there were 383 suicide deaths in men and 90 in women. Suicide mortality was higher in older men and women who experienced the loss compared to those who did not, and the impact of the spouse loss on mortality was stronger in men (age-adjusted MRR=2.83) than in women (1.41). Among men the excess risk was particularly high during the first year following the loss; in women, no substantial differences in the excess risk were observed over the follow-up period. CONCLUSION: Study findings provide evidence of the sex differences in the impact of spouse loss based on data from a large national cohort and reinforce the need for monitoring suicide risk in recently widowed older people.

The role of echocardiographic assessment for the risk of adverse events in liver transplant recipients: A systematic review and meta-analysis.

BACKGROUND & AIMS: Echocardiographic findings may provide valuable information about the cardiac conditions in cirrhotic patients waiting for liver transplantation (LT). However, data on the ability of the different echocardiographic parameters to predict post-transplant risk of mortality are scarce and heterogeneous. This systematic review evaluates the role of different echocardiographic features as predictors of post-LT mortality. A meta-analysis was also performed according to the observed results. METHODS: A systematic review was conducted according to PRISMA guidelines. Medline (PubMed) database was searched through February 2023 for relevant published original articles reporting the prognostic value of echocardiographic findings associated with outcomes of adult LT recipients. The risk of bias in included articles was assessed using ROBINS-E tool. Methodological quality varied from low to high across the risk of bias domains. RESULTS: Twenty-three studies were identified after the selection process; ten were enrollable for the meta-analyses. According to the results observed, the E/A ratio fashioned as a continuous value (HR = 0.43, 95%CI = 0.25-0.76; P = 0.003), and tricuspid regurgitation (HR = 2.36, 95%CI = 1.05-5.31; P = 0.04) were relevant predicting variables for post-LT death. Other echocardiographic findings failed to merge with statistical relevance. CONCLUSION: Tricuspid regurgitation and left ventricular diastolic dysfunction play a role in the prediction of post-LT death. More studies are needed to clarify further the impact of these echocardiographic features in the transplantation setting.