Recent outcomes of liver transplantation for Budd-Chiari syndrome: A study of the European Liver Transplant Registry (ELTR) and affiliated centers.

BACKGROUND AND AIMS: Management of Budd-Chiari syndrome (BCS) has improved over the last decades. The main aim was to evaluate the contemporary post-liver transplant (post-LT) outcomes in Europe. APPROACH AND RESULTS: Data from all patients who underwent transplantation from 1976 to 2020 was obtained from the European Liver Transplant Registry (ELTR). Patients < 16 years, with secondary BCS or HCC were excluded. Patient survival (PS) and graft survival (GS) before and after 2000 were compared. Multivariate Cox regression analysis identified predictors of PS and GS after 2000. Supplemental data was requested from all ELTR-affiliated centers and received from 44. In all, 808 patients underwent transplantation between 2000 and 2020. One-, 5- and 10-year PS was 84%, 77%, and 68%, and GS was 79%, 70%, and 62%, respectively. Both significantly improved compared to outcomes before 2000 ( p < 0.001). Median follow-up was 50 months and retransplantation rate was 12%. Recipient age (aHR:1.04,95%CI:1.02-1.06) and MELD score (aHR:1.04,95%CI:1.01-1.06), especially above 30, were associated with worse PS, while male sex had better outcomes (aHR:0.63,95%CI:0.41-0.96). Donor age was associated with worse PS (aHR:1.01,95%CI:1.00-1.03) and GS (aHR:1.02,95%CI:1.01-1.03). In 353 patients (44%) with supplemental data, 33% had myeloproliferative neoplasm, 20% underwent TIPS pre-LT, and 85% used anticoagulation post-LT. Post-LT anticoagulation was associated with improved PS (aHR:0.29,95%CI:0.16-0.54) and GS (aHR:0.48,95%CI:0.29-0.81). Hepatic artery thrombosis and portal vein thrombosis (PVT) occurred in 9% and 7%, while recurrent BCS was rare (3%). CONCLUSIONS: LT for BCS results in excellent patient- and graft-survival. Older recipient or donor age and higher MELD are associated with poorer outcomes, while long-term anticoagulation improves both patient and graft outcomes.

Distinguishing Features of Autoimmune Gastritis Depending on Previous Helicobacter pylori Infection or Positivity to Anti-Parietal Cell Antibodies: Results From the Autoimmune gastRitis Italian netwOrk Study grOup (ARIOSO).

INTRODUCTION: To describe the clinical features and the risk of developing gastric tumors in patients with autoimmune gastritis (AIG). METHODS: This was a retrospective, longitudinal, multicenter study conducted at 8 Italian tertiary referral centers. We retrieved clinical data from all histologically proven patients with AIG. Differences between Helicobacter pylori -exposed vs H. pylori -naive and anti-parietal cell antibody (PCA)-positive vs PCA-negative patients were investigated. The rate of gastric adenocarcinoma and type 1 gastric neuroendocrine neoplasm (gNEN) was assessed. A multivariable model for factors associated with gNEN was fitted. RESULTS: A total of 1,598 patients with AIG (median age 58 years, interquartile range 46-68; F:M ratio 2.7:1) were included. H. pylori -naive patients were more likely to have a first-degree family history of AIG (14.7% vs 8.9%; P = 0.012), type 1 diabetes mellitus (4.9% vs 2.3%; P = 0.025), and pernicious anemia (30.9% vs 21.1%; P = 0.003). PCA-positive patients had significantly more associated autoimmune diseases (59.0% vs 42.9%; P < 0.001) and were more likely to have been diagnosed by a case-finding strategy (15.3% vs 2.6%; P < 0.001). Overall, 15 cases (0.9%) of gastric adenocarcinoma and 153 cases (9.6%) of gNEN occurred, with a global rate of 0.12 (95% confidence interval [CI] 0.07-0.20) and 1.22 (95% CI 1.03-1.42) per 100 person/year, respectively. Having a vitamin B12/iron deficiency manifestation at AIG diagnosis was associated with a 16.44 (95% CI 9.94-27.20 P < 0.001) hazard ratio of gNEN. DISCUSSION: The "pure" AIG pattern has typical features of an autoimmune disease and seems to be unrelated to H. pylori . In a tertiary referral setting, the risk of developing overt gastric adenocarcinoma is low, while patients with vitamin B12 deficiency complications at onset may benefit from a more intense endoscopic follow-up for early gNEN detection.

Small bowel lesions in patients with iron deficiency anaemia without overt bleeding: a multicentre study.

The diagnostic work-up in iron deficiency anaemia (IDA) patients can be challenging when bleedings or malabsorption are not clinically manifest. Lesions on the small bowel mucosa may cause IDA. We evaluated the prevalence of lesions on the small bowel mucosa detected at Videocapsule Endoscopy (VCE) in IDA patients following negative upper and lower endoscopies. Clinical and endoscopic data collected in 5 centres were retrieved. Lesions with a high bleeding potential (P2) were computed, and predictive factors investigated at multivariate analysis. By considering data of 230 patients, the endoscopic examination detected a total of 96 (41.7%; 95% CI: 35.4-48.1) P2 lesions on the small bowel mucosa, including 4 (1.7%) cancers. The use of non-steroidal anti-inflammatory drugs was found to be the only associated factor at both univariate (OR: 5.7, 95% CI: 2.4-13.4; P <0.001) and multivariate (OR: 2.8; 95% CI: 1.7-3.9, P <0.01) analyses. Present study showed that evaluation of small bowel mucosa with VCE allows to disclose a potential cause of IDA in near half patients. The cooperation between haematologists and gastroenterologists in the diagnostic work-up may be useful.

Diagnostic Yield of Small Bowel Videocapsule Endoscopy in Patients with Iron Deficiency Anemia. A Systematic Review and meta-analysis.

BACKGROUND AND AIM: Gastrointestinal (GI) bleeding or malabsorption represents the most frequent aetiologies of iron deficiency anemia (IDA). The cause of IDA remains undetermined in ~10% to 20% of patients undergoing upper and lower GI endoscopies. In this scenario, a small bowel examination with videocapsule endoscopy (VCE) is recommended. We performed a systematic review with meta-analysis to evaluate the diagnostic yield of VCE in patients with IDA without overt bleeding, assessing the prevalence of either any lesion or lesions at high potential of bleeding. MATERIALS AND METHODS: A computerized literature search was performed using relevant keywords to identify all the pertinent articles published until March 2023. RESULTS: Twelve studies with a total of 1703 IDA patients (Males: 47%; age range: 19-92 y) were included in this systematic review. The diagnostic yield of VCE for overall lesions in the small bowel was 61% (95% CI=44-77; 95 CI=97.2-98.1; I2=97.7%). When analyzing only small bowel lesions likely responsible of IDA, the diagnostic yield was 40% (95% CI=27-53; 95% CI=95.3-97; I2=96.3%). CONCLUSION: VCE plays a relevant role in the diagnostic work-up of patients with IDA without overt bleeding with a satisfactory diagnostic yield.

Cognitive, psychological, and physiological effects of a web-based mindfulness intervention in older adults during the COVID-19 pandemic: an open study.

BACKGROUND: The development of effective strategies to maintain good mental health of older adults is a public health priority. Mindfulness-based interventions have the potential to improve psychological well-being and cognitive functions of older adults, but little is known about the effect of such interventions when delivered through internet. During the COVID-19 pandemic we evaluated short- and long-term cognitive, psychological, and physiological effects of a mindfulness-based intervention (MBI) delivered via web-based videoconference in healthy older adults. METHODS: Fifty older adults participated in an 8-week MBI, which comprised structured 2-h weekly group sessions. A comprehensive evaluation encompassing cognitive (verbal memory, attention and processing speed, executive functions) and psychological assessments (depression and anxiety symptoms, mindfulness, worries, emotion regulation strategies, well-being, interoceptive awareness and sleep) was conducted. Additionally, electroencephalography (EEG) data were recorded before and after the MBI and at the 6-month follow-up (T6). Data were analyzed using an intention-to-treat approach, using linear mixed models adjusted for age. The effect size for time was computed as omega squared. RESULTS: We observed significant improvements from pre-MBI to post-MBI and at the T6 across several measures. These improvements were notable in the areas of verbal memory (California Verbal Learning Test, p ≤ .007), attention and executive functions (Trail Making Test A and BA, p < .050), interoceptive awareness (Multidimensional Assessment of Interoceptive Awareness, p = .0002 for self-regulation and p < .05 for noticing, body listening, and trusting dimensions), and rumination (Heidelberg Form for Emotion Regulation Strategies, p = .018). These changes were associated with low to medium effect size. Moreover, we observed significant changes in EEG patterns, with a decrease in alpha1 (p = .004) and an increase in alpha2 (p < .0001) from pre-MBI to T6. Notably, improvements in TMTBA and rumination were correlated with the decrease in alpha1 (p < .050), while improvements in TMTA were linked to the increase in alpha2 (p = .025). CONCLUSIONS: The results of our study show that a web-based MBI in older adults leads to improvements in cognitive and psychological measures, with associated modulations in specific brain rhythms. While these findings are promising, further controlled studies are required to validate these preliminary results. TRIAL REGISTRATION: The trial has been registered with the United States National Library of Medicine at the National Institutes of Health Registry of Clinical Trials under the code NCT05941143 on July 12, 2023.

Artificial Intelligence-Powered Molecular Docking and Steered Molecular Dynamics for Accurate scFv Selection of Anti-CD30 Chimeric Antigen Receptors.

Chimeric antigen receptor (CAR) T cells represent a revolutionary immunotherapy that allows specific tumor recognition by a unique single-chain fragment variable (scFv) derived from monoclonal antibodies (mAbs). scFv selection is consequently a fundamental step for CAR construction, to ensure accurate and effective CAR signaling toward tumor antigen binding. However, conventional in vitro and in vivo biological approaches to compare different scFv-derived CARs are expensive and labor-intensive. With the aim to predict the finest scFv binding before CAR-T cell engineering, we performed artificial intelligence (AI)-guided molecular docking and steered molecular dynamics analysis of different anti-CD30 mAb clones. Virtual computational scFv screening showed comparable results to surface plasmon resonance (SPR) and functional CAR-T cell in vitro and in vivo assays, respectively, in terms of binding capacity and anti-tumor efficacy. The proposed fast and low-cost in silico analysis has the potential to advance the development of novel CAR constructs, with a substantial impact on reducing time, costs, and the need for laboratory animal use.

Novel NPM1 exon 5 mutations and gene fusions leading to aberrant cytoplasmic nucleophosmin in AML.

Nucleophosmin (NPM1) mutations in acute myeloid leukemia (AML) affect exon 12, but also sporadically affect exons 9 and 11, causing changes at the protein C-terminal end (tryptophan loss, nuclear export signal [NES] motif creation) that lead to aberrant cytoplasmic NPM1 (NPM1c+), detectable by immunohistochemistry. Combining immunohistochemistry and molecular analyses in 929 patients with AML, we found non-exon 12 NPM1 mutations in 5 (1.3%) of 387 NPM1c+ cases. Besides mutations in exons 9 (n = 1) and 11 (n = 1), novel exon 5 mutations were discovered (n = 3). Another exon 5 mutation was identified in an additional 141 patients with AML selected for wild-type NPM1 exon 12. Three NPM1 rearrangements (NPM1/RPP30, NPM1/SETBP1, NPM1/CCDC28A) were detected and characterized among 13 979 AML samples screened by cytogenetic/fluorescence in situ hybridization and RNA sequencing. Functional studies demonstrated that in AML cases, new NPM1 proteins harbored an efficient extra NES, either newly created or already present in the fusion partner, ensuring its cytoplasmic accumulation. Our findings support NPM1 cytoplasmic relocation as critical for leukemogenesis and reinforce the role of immunohistochemistry in predicting AML-associated NPM1 genetic lesions. This study highlights the need to develop new assays for molecular diagnosis and monitoring of NPM1-mutated AML.

Children under 6 years with acute headache in Pediatric Emergency Departments. A 2-year retrospective exploratory multicenter Italian study.

BACKGROUND: Preschool age (i.e. children under six years of age) represents a red flag for requiring neuroimaging to exclude secondary potentially urgent intracranial conditions (PUIC) in patients with acute headache. We investigated the clinical characteristics of preschoolers with headache to identify the features associated with a greater risk of secondary "dangerous" headache. METHODS: We performed a multicenter exploratory retrospective study in Italy from January 2017 to December 2018. Preschoolers with new-onset non-traumatic headache admitted to emergency department were included and were subsequently divided into two groups: hospitalized and discharged. Among hospitalized patients, we investigated the characteristics linked to potentially urgent intracranial conditions. RESULTS: We included 1455 preschoolers with acute headache. Vomiting, ocular motility disorders, ataxia, presence of neurological symptoms and signs, torticollis and nocturnal awakening were significantly associated to hospitalization. Among the 95 hospitalized patients, 34 (2.3%) had potentially urgent intracranial conditions and more frequently they had neurological symptoms and signs, papilledema, ataxia, cranial nerves paralysis, nocturnal awakening and vomiting. Nevertheless, on multivariable logistic regression analysis, we found that only ataxia and vomiting were associated with potentially urgent intracranial conditions. CONCLUSION: Our study identified clinical features that should be carefully evaluated in the emergency department in order to obtain a prompt diagnosis and treatment of potentially urgent intracranial conditions. The prevalence of potentially urgent intracranial conditions was low in the emergency department, which may suggest that age under six should not be considered an important risk factor for malignant causes as previously thought.

Individual risk prediction of high grade prostate cancer based on the combination between total prostate-specific antigen (PSA) and free to total PSA ratio.

OBJECTIVES: Clinical practice guidelines endorse the stratification of prostate cancer (PCa) risk according to individual total prostate-specific antigen (tPSA) values and age to enhance the individual risk-benefit ratio. We defined two nomograms to predict the individual risk of high and low grade PCa by combining the assay of tPSA and %free/tPSA (%f/tPSA) in patients with a pre-biopsy tPSA between 2 and 10 µg/L. METHODS: The study cohort consisted of 662 patients that had fPSA, tPSA, and a biopsy performed (41.3% with a final diagnosis of PCa). Logistic regression including age, tPSA and %f/tPSA was used to model the probability of having high or low grade cancer by defining 3 outcome levels: no PCa, low grade (International Society of Urological Pathology grade, ISUP<3) and high grade PCa (ISUP≥3). RESULTS: The nomogram identifying patients with: (a) high vs. those with low grade PCa and without the disease showed a good discriminating capability (∼80%), but the calibration showed a risk of underestimation for predictive probabilities >30% (a considerable critical threshold of risk), (b) ISUP<3 vs. those without the disease showed a discriminating capability of 63% and overestimates predictive probabilities >50%. In ISUP 5 a possible loss of PSA immunoreactivity has been observed. CONCLUSIONS: The estimated risk of high or low grade PCa by the nomograms may be of aid in the decision-making process, in particular in the case of critical comorbidities and when the digital rectal examinations are inconclusive. The improved characterization of the risk of ISUP≥3 might enhance the use for magnetic resonance imaging in this setting.

Italian Versions of the 12-Item Sexual Distress Scale (SDS) and the 5-Item Sexual Distress Scale-Short Form (SDS-SF): Psychometric Properties.

The study aimed to analyze the psychometric properties of the Italian versions of the 12-item Sexual Distress Scale (SDS) and the 5-item Sexual Distress Scale-Short Form (SDS-SF). A total sample of 2291 adults (1361 women, 930 men) participated through a web survey completing the SDS, the FSFI, the IIEF, the PANAS and the SCL-90-R. The results supported the adequacy of both the SDS and SDS-SF factor structures, good reliability (respectively, α = .96 and .92), discriminant validities and strong associations with satisfaction, fear, depression, and psychoticism. SDS and SDS-SF may facilitate the assessment of sexual distress for both clinical and research purposes.

Small Bowel Imaging in Celiac Disease: Is there a role for Small Bowel Ultrasound?

PURPOSE OF REVIEW: The incidence of celiac disease (CD) has increased over the last decades in part due to better disease awareness. Small bowel ultrasound (sb US) enables dynamic assessment of the bowel; although this topic has been addressed, the use of sb US in the diagnosis and in the follow-up of CD patients is limited to a few specialized tertiary referral centers. Herein, we aimed at summarizing the available literature on this topic to better define the potential clinical implications of sb US in CD, also through a comparison with other available diagnostic techniques. RECENT FINDINGS: According to available data, sb US can be of help in confirming or excluding CD in patients with clinical suspicion; specifically, the finding of increased gall bladder volume, free abdominal fluid and enlargement of mesenteric lymph nodes reliably and accurately predicts the diagnosis of CD, whereas the absence of bowel dilatation and increased peristalsis may exclude the diagnosis. However, the place of intestinal US in the diagnostic algorithm of CD is likely to vary depending on the probability of the disease in a given population. There are only a few studies on the role of sb US in complicated CD, even if recent reports suggest a possible clinical role. There is a lack of data on follow-up of CD patients, particularly with the aim of detecting a poor diet adherence. According to current data sb US parameters have been shown to be of value in confirming and excluding the diagnosis of CD. Prospective studies with large sample size are warranted to determine whether to include sb US in the available guidelines for CD diagnosis and monitoring.

Validation of the Italian Version of the Daily Spiritual Experience Scale Among Psychiatric Patients.

Spiritual experience can represent an important aspect of mental health. The purpose of the current study was to validate the Italian version of the Daily Spiritual Experience Scale (DSES-IT) in a population of patients with different psychiatric disorders. It involved 209 patients enrolled in four facilities within the network of IRCCS Centro San Giovanni di Dio Fatebenefratelli Research Institute in Italy. The exploratory factor analysis (EFA) indicated two domains. Internal consistency was very good (Cronbach's Alpha = .93). Scale stability across time assessed by test-retest reliability showed a good performance (Pearson's correlation r > 0.9 for all items). Convergent reliability was assessed by Pearson's correlation between the DSES-IT and the WHOQOL-SRPB scales (r = - .63, p = 0.001). Diagnostic group comparison revealed a statistically significant difference among the patient groups (ANOVA test p = 0.01). The results confirm good psychometric properties of the Italian version of the DSES scale.

Long-term outcomes of resection versus transplantation for neuroendocrine liver metastases meeting the Milan criteria.

Liver resection (LR) is considered the treatment of choice for resectable neuroendocrine liver metastases (NELM), while liver transplantation (LT) is currently reserved for highly selected unresectable patients. We retrospectively analyzed data from consecutive patients undergoing either curative resection or transplantation for liver-only NELM meeting Milan criteria at a single center between 1984 and 2019. Patients who fit Milan criteria were 48 in the transplantation group and 56 in the resection group. After a median follow-up of 158 months for the transplantation group and 126 for the resection group, the 10-year survival rate was 93% for transplantation and 75% for resection (p = .007). The 10-year disease-free survival rate was 52% for transplantation and 18% for resection (p < .001). Transplantation was associated with improved survival at univariate analysis. The median disease-free interval between surgery and recurrence was 78 months for transplantation vs. 24 months for resection (p < .001). The transplantation group had more multisite recurrences (12/25, 48% vs. 5/42, 12% in the resection group, p = .001), while most recurrences in the resection group were intra-hepatic (37/42, 88%, versus 2/25, 8% in the transplantation group). In conclusion, LT was associated with improved survival outcomes in NELM meeting the Milan criteria compared with LR.

Risk-tailored treatment of splenic marginal zone lymphoma.

Splenic marginal zone lymphoma (SMZL) is a rare lymphoproliferative disease involving B-cells and affecting elderly patients. SMZL plague peripheral blood and bone marrow, spleen. Lymph nodes are generally spared. SMZL is due to a protracted antigen stimulation of B lymphocytes and of microenvironment leading B-cell to polyclonal and then oligoclonal/monoclonal growth, promoting lymphoproliferation. Integration of the NOTCH2 and NFk-B signaling has been recently identified as the primary mechanism of neoplastic proliferation in SMZL. In total 20% of cases carry mutations in NOTCH2. Although SMZL has an indolent course, progression to diffuse large B-cell lymphoma occurs in about 10-15% of patients. Establishing the prognosis is a key step in disease management, depending on both individual risk and patients' health status. This review discusses tailored treatment of SMZL patients. Progression risk factors include nodal and extra-nodal involvement, peripheral lymphocytosis, anemia and thrombocytopenia. Patients with two or more score points have a median survival of <5 years. Watch and wait strategy is appropriate in low-risk and asymptomatic patients, whereas treatment of symptomatic patients ranges from splenectomy to rituximab monotherapy or associated with chemotherapy.

Clinical treatment of cholangiocarcinoma: an updated comprehensive review.

Cholangiocarcinoma (CCA) is a heterogeneous group of neoplasms of the bile ducts and represents the second most common hepatic cancer after hepatocellular carcinoma; it is sub-classified as intrahepatic cholangiocarcinoma (iCCA) and extrahepatic cholangiocarcinoma (eCCA), the latter comprising both perihilar cholangiocarcinoma (pCCA or Klatskin tumor), and distal cholangiocarcinoma (dCCA). The global incidence of CCA has increased worldwide in recent decades. Chronic inflammation of biliary epithelium and bile stasis represent the main risk factors shared by all CCA sub-types. When feasible, liver resection is the treatment of choice for CCA, followed by systemic chemotherapy with capecitabine. Liver transplants represent a treatment option in patients with very early iCCA, in referral centers only. CCA diagnosis is often performed at an advanced stage when CCA is unresectable. In this setting, systemic chemotherapy with gemcitabine and cisplatin represents the first treatment option, but the prognosis remains poor. In order to ameliorate patients' survival, new drugs have been studied in the last few years. Target therapies are directed against different molecules, which are altered in CCA cells. These therapies have been studied as second-line therapy, alone or in combination with chemotherapy. In the same setting, the immune checkpoints inhibitors targeting programmed death 1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte antigen-4 (CTLA-4), have been proposed, as well as cancer vaccines and adoptive cell therapy (ACT). These experimental treatments showed promising results and have been proposed as second- or third-line treatment, alone or in combination with chemotherapy or target therapies.

School-based interventions to improve emotional regulation skills in adolescent students: A systematic review.

INTRODUCTION: Emotional regulation (ER) is a core variable involved in the onset and maintenance of mental health disorders; therefore, interventions targeting ER in adolescence represent a promising preventive action. The current systematic review provides a synthesis of the evidence on school-based interventions on ER in adolescent students. METHODS: Six electronic databases (Medline, Psychology Database, Embase, Scopus, Psychinfo, and Web of Science) were searched. The methodological quality of the included studies was assessed by the Methodological Index for Nonrandomized Studies. RESULTS: A total of 36 studies were identified. The interventions were based on different theoretic frameworks and focused on different components of ER. There were universal interventions that addressed the entire class, as well as interventions for a selected population of at-risk students. Only one-third of the studies were based on manualized programs. Small to moderate effect sizes were found for mental health and ER skills. Only a few studies assessed risky behaviors, and these studies showed a reduction with moderate to large effect size. Studies conducted on high-risk populations showed medium-high effect sizes on ER skills. In contrast, studies conducted on unselected samples of students showed greater variability in the outcome estimates. Acceptability analysis and attendance rates suggested that the interventions were well received by students. The lack of follow-up assessments and the absence of sample-size calculation were the most frequent methodological weaknesses. CONCLUSIONS: The content of the present review could be useful for professionals involved in the planning of school psychological services. Overall, the findings of the current review support the applicability and beneficial effect of school-based intervention for adolescents. Moreover, the results clearly point out the utility of a multitiered model to structure coordinated and integrated preventive interventions and to optimize resources.

Double-Balloon Enteroscopy in Detecting Small-Bowel Neuroendocrine Neoplasms: A Single-Center Prospective Study.

BACKGROUND AND AIM: Small-bowel neuroendocrine neoplasm (sbNEN) diagnosis has improved with double-balloon enteroscopy (DBE). DBE efficacy in the detection of sbNENs is unknown. We aimed to report the experience at a single referral center for NENs. METHODS: All consecutive patients with a suspected sbNEN selected for diagnostic DBE were enrolled. RESULTS: Between 2011 and 2016, 25 patients were referred for a suspected sbNEN. In 15/25 patients, a primary NEN was detected outside the small bowel; in 4, NEN was excluded. After extensive workup, 6 patients (4 males, median age 50 years) underwent DBE (3 anterograde, 2 retrograde, and 1 both; median time: 60 min; median insertion 200 cm). DBE was positive in 3 patients: one had an ileal 2-cm NEN G1, one had an ileal 1.3-cm NEN G1, and one had an ileal 1-cm NEN G2, all surgically removed. Of the 3 other patients, one had a metastatic NEN of unknown primary, the other two had small intestinal NENs, both surgically removed (1.6-cm G1 and G2 NEN). DBE showed a sensitivity of 60% and, in absence of false-positive results, a specificity of 100%. Accuracy resulted 67%. No complications were observed. CONCLUSIONS: In line with data from the literature, the present series showed that DBE is a safe and effective procedure in the diagnosis of sbNENs. Further studies are needed to better clarify the diagnostic role of DBE in the neuroendocrine tumor setting and its relationship with other techniques.

Biliary Stone Disease in Patients with Neuroendocrine Tumors Treated with Somatostatin Analogs: A Multicenter Study.

BACKGROUND: Somatostatin analogs (SSAs) are the mainstay of neuroendocrine tumor (NET) treatment. Biliary stone disease is reported as a common side effect of SSAs, with a frequency ranging from 10% to 63%. Studies on SSA-treated patients for acromegaly report an increased incidence of biliary stone disease compared with the general population, whereas data on patients with NETs are few. Guidelines are based on weak evidence, thus resulting in conflicting recommendations. The aim of the study is to evaluate biliary stone disease incidence, complications, and risk factors in a large population of SSA-treated patients with NETs. MATERIALS AND METHODS: A retrospective analysis of a prospectively collected database was performed. Patients with a diagnosis of NET in seven dedicated centers from 1995 to 2017 were included at the time of SSA start. RESULTS: A total of 754 SSA-treated patients were evaluated. Patients with history of cholecystectomy or with known biliary stone disease were excluded; 478 patients were included. Among them, 118 patients (24.7%) received prophylactic ursodeoxycholic acid (UDCA). During the study period, 129 patients (27.0%) developed biliary stone disease; of them, 36 (27.9%) developed biliary complications. On multivariate analysis, primary gastrointestinal (GI)-NET (hazard ratio [HR] 1.76) and related surgery (HR 1.58) were independent risk factors for biliary stone disease. CONCLUSION: We report a high incidence of biliary stone disease particularly in GI-NET or GI surgery. UDCA prophylaxis does not seem to have a protective role. Our data suggest that all patients with primary GI-NET or undergoing abdominal surgery should be considered for prophylactic cholecystectomy; no conclusion could be drawn on the indication of prophylactic cholecystectomy in patients with primary pancreatic or thoracic NET for whom abdominal surgery is not planned. IMPLICATIONS FOR PRACTICE: The results of this study confirm an increased rate of gallstones development and related complications in patients with neuroendocrine tumors (NETs) treated with somatostatin analogs (SSAs). NETs of the gastrointestinal (GI) tract and related surgery are independent risk factors for biliary stone disease development. Therefore, all patients with primary GI-NET or undergoing abdominal surgery should be considered for prophylactic cholecystectomy. Data on other subgroups are not exhaustive, and management also evaluating additional clinical features (life expectancy, surgical and anesthesiological risks) should be considered. Prophylactic treatment with ursodeoxycholic acid does not seem to be a protective factor for SSA-related biliary stone disease.

Liver histopathology in severe COVID 19 respiratory failure is suggestive of vascular alterations.

SARS2-CoV-2 breakout in Italy caused a huge number of severely ill patients with a serious increase in mortality. Although lungs seem to be the main target of the infection, very few information are available about liver involvement, possibly evocating a systemic disease. Post-mortem wedge liver biopsies from 48 patients died from severe pulmonary COVID-19 disease with respiratory failure were collected from two main hospitals in northern Italy. No patient had clinical symptoms of liver disease or signs of liver failure before and during hospitalization; for each of them liver function tests were available. All liver samples showed minimal inflammation features. Histological pictures compatible with vascular alterations were observed, characterized by increase in number of portal vein branches associated with lumen massive dilatation, partial or complete luminal thrombosis of portal and sinusoidal vessels, fibrosis of portal tract, focally markedly enlarged and fibrotic. SARS-CoV-2 was found in 15 of 22 samples tested by in situ hybridization method. Our preliminary results confirm the clinical impression that liver failure is not a main concern and this organ is not the target of significant inflammatory damage. Histopathological findings are highly suggestive for marked derangement of intrahepatic blood vessel network secondary to systemic changes induced by virus that could target not only lung parenchyma but also cardiovascular system, coagulation cascade and endothelial layer of blood vessels. It still remains unclear if the mentioned changes are directly related to virus infection or if SARS-CoV-2 triggers a series of reactions leading to striking vascular alterations.

[COVID-19 and mental health services in Europe]. / COVID-19 e servizi di salute mentale in Europa.

The area of mental health is directly affected by the pandemic and its consequences, for various reasons: 1-the pandemic triggered a global lockdown, with dramatic socioeconomic and therefore psychosocial implications; 2-mental health services, which treat by definition a fragile population from the psychological, biological and social points of view, have a complex organizational frame, and it was expected that this would be affected (or overwhelmed) by the pandemic; 3-mental health services should, at least in theory, be able to help guide public health policies when these involve a significant modification of individual behaviour. It was conducted a narrative review of the publications produced by European researchers in the period February-June 2020 and indexed in PubMed. A total of 34 papers were analyzed, which document the profound clinical, organizational and procedural changes introduced in mental health services following this exceptional and largely unforeseen planetary event.Among the main innovations recorded everywhere, the strong push towards the use of telemedicine techniques should be mentioned: however, these require an adequate critical evaluation, which highlights their possibilities, limits, advantages and disadvantages instead of simple triumphalist judgments. Furthermore, should be emphasized the scarcity of quantitative studies conducted in this period and the absence of studies aimed, for example, at exploring the consequences of prolonged and forced face-to-face contact between patients and family members with a high index of "expressed emotions".