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Transabdominal ultrasound is a valuable diagnostic approach for evaluating the gastrointestinal tract and related disorders. This dynamic examination provides real-time visualization of the digestive tube and surrounding structures, assessment of peristaltic movements, estimation of compressibility of intestinal loops, and recognition of painful spots requiring specific attention. Since ultrasound imaging is non-invasive, painless, reproducible, inexpensive and requires no special preparation, it is used as a major diagnostic tool in emergency settings and in outpatient follow-up of several disorders. Costs, encompassing both accessibility and actual procedural expenses, are lower than those associated with other diagnostic techniques. However, the incorporation of gastro-intestinal ultrasound (GIUS) in clinical practice has not been widely used on a global scale. The purpose of this paper is to provide an overview of the execution techniques as well as the main areas of application for GIUS. Through illustrative iconographic representation, emphasis was placed on its potential within the diagnostic and therapeutic pathway of various acute and chronic gastrointestinal disorders.

Abstract Immune cell-derived extracellular vesicles (EV) affect tumor progression and hold promise for therapeutic applications. Eosinophils are major effectors in Th2-related pathologies recently implied in cancer. Here, we evaluated the anti-tumor activities of eosinophil-derived EV following activation with the alarmin IL-33. We demonstrate that IL-33-activated mouse and human eosinophils produce higher quantities of EV with respect to eosinophils stimulated with IL-5. Following incorporation of EV from IL-33-activated eosinophils (Eo33-EV), but not EV from IL-5-treated eosinophils (Eo5-EV), mouse and human tumor cells increased the expression of cyclin-dependent kinase inhibitor (CDKI)-related genes resulting in cell cycle arrest in G0/G1, reduced proliferation and inhibited tumor spheroid formation. Moreover, tumor cells incorporating Eo33-EV acquired an epithelial-like phenotype characterized by E-Cadherin up-regulation, N-Cadherin downregulation, reduced cell elongation and migratory extent in vitro, and impaired capacity to metastasize to lungs when injected in syngeneic mice. RNA sequencing revealed distinct mRNA signatures in Eo33-EV and Eo5-EV with increased presence of tumor suppressor genes and enrichment in pathways related to epithelial phenotypes and negative regulation of cellular processes in Eo33-EV compared to Eo5-EV. Our studies underscore novel IL-33-stimulated anticancer activities of eosinophils through EV-mediated reprogramming of tumor cells opening perspectives on the use of eosinophil-derived EV in cancer therapy.

Background and aimsENHANCE was a phase 3 study that evaluated efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-δ (PPAR) agonist, versus placebo in patients with primary biliary cholangitis with inadequate response or intolerance to ursodeoxycholic acid (UDCA).Approach and resultsPatients were randomized 1:1:1 to oral seladelpar 5 mg (n=89), 10 mg (n=89), placebo (n=87) daily (with UDCA, as appropriate). Primary end point was a composite biochemical response [alkaline phosphatase (ALP) < 1.67×upper limit of normal (ULN), ≥15% ALP decrease from baseline, and total bilirubin ≤ ULN] at month 12. Key secondary end points were ALP normalization at month 12 and change in pruritus numerical rating scale (NRS) at month 6 in patients with baseline score ≥4. Aminotransferases were assessed. ENHANCE was terminated early following an erroneous safety signal in a concurrent, NASH trial. While blinded, primary and secondary efficacy end points were amended to month 3. Significantly more patients receiving seladelpar met the primary end point (seladelpar 5 mg: 57.1%, 10 mg: 78.2%) versus placebo (12.5%) ( p < 0.0001). ALP normalization occurred in 5.4% ( p =0.08) and 27.3% ( p < 0.0001) of patients receiving 5 and 10 mg seladelpar, respectively, versus 0% receiving placebo. Seladelpar 10 mg significantly reduced mean pruritus NRS versus placebo [10 mg: -3.14 ( p =0.02); placebo: -1.55]. Alanine aminotransferase decreased significantly with seladelpar versus placebo [5 mg: 23.4% ( p =0.0008); 10 mg: 16.7% ( p =0.03); placebo: 4%]. There were no serious treatment-related adverse events.ConclusionsPatients with primary biliary cholangitis (PBC) with inadequate response or intolerance to UDCA who were treated with seladelpar 10 mg had significant improvements in liver biochemistry and pruritus. Seladelpar appeared safe and well tolerated.

Background: The risk of hepatocarcinoma in HCV cirrhotic patient responders after treatment with DAAs decrease, but HCC still occurs. A correlation between specific miRNAs and the development of hepatocarcinoma have been highlighted. Aim: To investigate miRNA expression in HCV-infected cirrhotic patients treated with DAAs, regarding whether or not they developed HCC at follow-up. Methods: A total of 73 outpatients with HCV-related cirrhosis treated with DAAs were enrolled, 28 of which had HCC. Samples were collected at the start and at the end of treatment. In the screening phase, 172 miRNAs were analyzed at baseline. Differentially expressed miRNAs were validated in the entire cohort. Results: In the validation phase, at baseline and in patients treated for 12 weeks, miR-28-5p was confirmed to be more highly expressed in the HCC group compared to the non-HCC group. In all of the patients treated for 12 weeks, at end of the treatment we found a significant downregulation in miR-132-3p, miR-133b-3p, miR-221-3p and miR-324-3p. In the HCC group, miR-28-5p was significantly downregulated after DAA therapy as well as in HCC patients treated for 24 weeks. Conclusion: In the HCC group, miR28-5p was differently expressed both at baseline and at the end of therapy with DAAs. This difference in expression should suggest its involvement in HCC development.

IntroductionIn 2021 ofatumumab, a recombinant human anti-CD20 monoclonal antibody (mAb) already authorized for the treatment of chronic lymphocytic leukemia, received the marketing approval for the treatment of relapsing forms of multiple sclerosis (MS). Differently from ocrelizumab, that is administered intravenously, ofatumumab if the first anti-CD20 mAb to be administered subcutaneously without a premedication.Methods and objectivesIn this study we aimed to describe and compare the main characteristics of Individual Case Safety Reports (ICSRs) describing the occurrence of Injective Related Reactions (IRRs) following the treatment with ocrelizumab and ofatumumab reported in the Eudravigilance (EV) database during years 2021–2023.ResultsA total of 860 ICSRs with either ofatumumab and ocrelizumab as suspected drug were retrieved from Eudravigilance, of which 51% associated with ofatumumab and 49% with ocrelizumab. The majority of patients who experienced IRRs following ocrelizumab belonged to the age group of 18–64 years (73%), while the age-group was mostly not specified (55%) in ICSRs reporting ofatumumab as suspected. The distribution of gender was almost similar in the two groups, with the majority of ICSRs related to female patients. “Pyrexia” was the Preferred Term (PT) most reported for ofatumumab, while “Infusion related reaction” were more frequently reported with ocrelizumab. Premedication drugs were reported in 148 ICSRs. Out of 89 ICSRs for which the Time to Event (TTE) was calculated, 74 reported IRRs that occurred the same day of the drug administration.DiscussionBased on the results of this study, although a risk of ofatumumab-induced IRRs cannot be excluded, it should be considered as manageable considering that the drug seems to be mostly associated with the occurrence of fever. Thus, it is important to continue to closely monitor the use of these in clinical practice to improve the knowledge on their long-term safety.

IntroductionDisease modifying therapies (DMTs) used to treat multiple sclerosis (MS) can be associated to the occurrence of hematological disorders. This systematic review aims to provide an overview of these events occurring in real-life conditions, by describing case reports and series published in the literature.MethodsA literature search of all publications up to January 5th 2024 on the Medline and Embase databases was carried out. The results were presented both in the text and in tables.ResultsSixty-seven case reports/series were included in this review, of which more than half related to alemtuzumab, natalizumab and ocrelizumab. The publication date of included studies ranged from 2006 to 2024. The majority of case reports and series described the occurrence of late-onset hematological disorders (events that occurred more than 30 days after the first DMT administration), mainly represented by case of neutropenia, autoimmune hemolytic anemia and immune thrombocytopenia. All cases reported a favorable outcome, apart one case report that described a fatal case. Among included cases, 4 articles, all related to natalizumab, described the occurrence of myeloid disorders in 13 newborns from mother receiving the DMT.DiscussionConsidering the limitations identified in the majority of included studies, further ad hoc studies are strongly needed to better evaluate the hematological disorders of DMTs. Meantime, the strict monitoring of treated patients for the occurrence of these toxicities should be highly recommended.

Wildlife tourism and wildlife trade may appear juxtaposed, but are two, potentially aligning, income generators that could benefit conservation in developing countries. Utilising data sets collated from Madagascar’s Ministère du Tourisme and CITES, respectively, for the period 2007 to 2018, this study estimated levels of income from wildlife tourism and wildlife trade for Madagascar. Between 2007 and 2018, tourism reported yearly incomes ranging from a low of USD 1.4 million up to a high of USD 15.7 million. However, it was unclear what percentage of this figure flowed to benefit local communities. Alternatively, using reported networks for the live wildlife trade, the estimated economic value reaching collectors and/or intermediaries in Madagascar was USD 72,299.80 for the period 2007 to 2018. Both revenue generators operated within different geographical areas, with tourism opportunities presenting themselves to communities adjacent to national parks, while wildlife trade networks were not restricted to protected areas and operated sporadically across Madagascar. Hence, the economic benefits reached different Malagasy participants across the country. The management of both activities needs great care to ensure that environmental impacts and sustainability are core measures on any such activities. Whilst this study shines a light on economic values and novel perspectives regarding these two trade types, it also highlights knowledge gaps, thus indicating where much greater research attentions are required to allow a better understanding of the specific benefits and risks from engaging with both trade types for local Malagasy people and their environments.

Using an integrative taxonomic approach including genetic and morphological data, we formally describe a new microendemic gecko species belonging to the Paroedura bastardi clade, previously referred to as P. bastardi D. We name this taxon currently known from Anja Reserve and Tsaranoro Valley Forest (south-central Madagascar), as P. manongavato sp. nov. The new species differs from other species of the P. bastardi clade by ≥ 12.4% uncorrected p-distance at the mitochondrial 16S rRNA gene and it forms a monophyletic group in the COI mtDNA phylogenetic tree. It lacks haplotype sharing at the nuclear KIAA1239 and CMOS genes with the other species of the same complex, including the syntopic P. rennerae. Given its limited extent of occurrence and high levels of habitat fragmentation linked to forest clearances and fires, we propose the IUCN Red List Category of Critically Endangered, based on the B1ab(iii) criterion. The conservation value of Anja Reserve and Tsaranoro Valley Forest is remarkable. Preserving the remaining deciduous forest habitat is of paramount importance to protect these narrow-range reptile species.

Frailty is a multidimensional syndrome predominantly studied in the elderly, characterized by reduced resistance to stressors due to diminished physiological reserve and resilience. Advances in surgical techniques and immunosuppressive drugs have improved long-term survival rates in solid organ transplant recipients, yet the 10-year survival is satisfying. However, liver transplant recipients have a noteworthy risk of developing frailty status. After liver transplant, frailty can be favored by socioeconomic, cultural, and health-related factors, leading to increased risks of hospitalization, morbidity, and mortality. Various tools for frailty assessment exist, but none are universally validated for post-transplant patients. The integration of socioeconomic and psychological factors into frailty evaluation could improve quality of life and long-term outcomes for transplant recipients. Multidisciplinary approaches, including psychosocial support, are essential for managing frailty and enhancing the overall care of transplanted patients. This narrative review aims to comprehensively address the principal frailty risk factors associated with liver transplantation.

Coatings play a crucial role in the functionality of vacuum chambers in particle accelerators, serving a dual goal by efficiently facilitating pumping and mitigating electron cloud effects. However, their impact on the surface impedance of the chamber walls raises concerns, potentially affecting the machine performance and imposing limitations on achievable energies and currents. Therefore, an electromagnetic characterization is essential for a comprehensive study of accelerator structures, particularly in the context of the next-generation machines where the demand for extremely short particle bunches accentuates the importance of evaluating material responses in the very-high-frequency region. We present a technique for probing the sub-THz response of coating materials by measuring pulsed signals passing through a specifically designed waveguide, in which is placed a slab with the deposited material under test. The proposed methodology allows for a comprehensive exploration of the electromagnetic properties of the most used technical surfaces (substrate plus coatings) in accelerators under realistic conditions, providing valuable insights into their behavior in the sub-THz frequency range. The experimental data of three different Non-Evaporable Getter coating samples, prepared on a copper substrate at the CERN deposition facilities under different sputtering conditions, are discussed. The findings contribute to a deeper understanding of the complex interactions between coatings and accelerator structures, with the aim of optimizing performance and efficiency in the evolving landscape of particle acceleration technologies. The limitations and advantages of the technique are also reported.

Madagascar is well known for its exceptional biodiversity and striking endemicity levels, which are accompanied by high rates of deforestation and habitat alteration [...]

Alessandra Bartoli,1,2 Carmela Cursaro,1 Hajrie Seferi,1 Pietro Andreone3,4 1Division of Internal Medicine and Metabolism, Department of Internal Medicine, Ospedale Civile di Baggiovara, University of Modena and Reggio Emilia, Modena, Italy; 2Post Graduate School of Allergy and Clinical Immunology, Department of Internal Medicine, University of Modena and Reggio Emilia, Modena, Italy; 3Chief of Division of Internal Medicine and metabolism, Department of Internal Medicine, University Hospital of Modena, Modena, Italy; 4Chief of Post Graduate School of Allergy and Clinical Immunology, Department of Internal Medicine, University of Modena and Reggio Emilia, Modena, ItalyCorrespondence: Alessandra Bartoli, University of Modena and Reggio Emilia, Ospedale Civile di Baggiovara, Via Pietro Giardini 1355, Baggiovara, MO, 41126, Italy, Email alessandra.bartoli25@yahoo.comPurpose: From the beginning of the Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV2) pandemic, different cases of a cholangiopathy with features of secondary sclerosing cholangitis in critically ill patients (SSC-CIP) have been reported. Patients developing it are generally recovering from severe Coronavirus disease 19 (COVID-19) and required intensive care unit (ICU) admission and mechanical ventilation. Many of them have been administered with ketamine during their ICU stay. The pathogenesis of this novel disease is still debated, and, since prognosis is poor, efforts are needed in order to better understand it.Patients and Methods: In this review, we focused our attention on COVID-19 SSC clinical, imaging, and histology findings in order to clarify the different pathogenetic options, particularly in regard of the ischemic-direct viral damage and ketamine-related theories, beginning with a recapitulation of SSC-CIP and ketamine-induced cholangiopathy in abusers. The research has been conducted using PubMed and Google Scholar databases. Key-words were “Secondary Sclerosing Cholangiopathy”, “SSC-CIP”, “Secondary Sclerosing Cholangiopathy in critically ill patients”, “Ketamine and cholangiopathy”, “Ketamine abusers and liver disease”, “Ketamine-related cholangiopathy”, “SARS-CoV2 infection and liver disease”, “post Covid-19 secondary sclerosing cholangitis”, “Covid-19 cholangiopathy”.Results: Many authors, based on the clinical, histological, imaging, and prognostic features of the disease, have pointed out the similarities between post COVID-19 SSC and SSC-CIP; however, peculiar features in the former were not previously observed. Therefore, a direct viral cytopathic action and SARS-CoV2-related coagulopathy are considered the most likely causes. On the other hand, ketamine, with the available data, cannot be surely linked as the main determinant cause of cholangiopathy. Moreover, ketamine-induced cholangitis (KIC) presentation is different from post COVID-19 SSC. Its role as a cofactor precipitating the disease cannot be ruled out.Conclusion: Post COVID-19 SSC is a rare clinical entity following severe COVID-19 disease. The most accepted theory is that a sum of different insults determines the disease: biliary ischemia, direct viral damage, toxic bile, possibly worsened by ketamine and hyperinflammation due to the cytokine storm. Given the severe prognosis of the disease, with persistent cholangiopathy, organ failure, and orthotopic liver transplantation (OLT), further study on this novel clinical entity is needed.Keywords: SARS-CoV2, cholangiopathy, secondary sclerosing cholangiopathy, ICU, SSC-CIP, ketamine, COVID-19 coagulopathy, direct viral damage

Endovascular thrombectomy is the standard treatment in selected patients with acute ischemic stroke and large vessel occlusion, but continuous improvement in angiographic and clinical outcome is still needed. Intra-arterial thrombolysis has been tested as a possible rescue tool in unsuccessful thrombectomy, or as an adjuvant therapy after the endovascular procedure, to pursue complete recanalization. Here we present a case series analysis of intra-arterial alteplase administration (5 mg bolus, repeated up to 15 mg if Thrombolysis in Cerebral Infarction (TICI) scale ≥2c is not achieved) in 15 consecutive anterior circulation stroke patients after unsuccessful thrombectomy, defined as TICI score ≤2b after at least 3 passes or if unsuitable for further endovascular attempts, with the aim of improving recanalization. An improvement of final TICI score was achieved in 10 of 15 patients (66.7%). TICI score ≥2c was achieved after 5 mg intra-arterial tissue plasminogen activator (iaTPA) in 4 patients, and after 10 mg iaTPA in 5 cases. Six of 15 patients received 15 mg iaTPA: 1 of 6 showed angiographical improvement. A major effect of intra-arterial alteplase was observed for distally migrated emboli. None of the patients experienced any symptomatic hemorrhagic transformation or other major bleeding. Our report shows, in a very small cohort, a high rate of final TICI score improvement, encouraging the development of randomized controlled trials of rescue intra-arterial thrombolysis in patients with suboptimal angiographic results after mechanical thrombectomy.

Antiphospholipid syndrome (APS) is an autoimmune prothrombotic condition characterized by venous thromboembolism, arterial thrombosis, and pregnancy morbidity. Among neurological manifestations, arterial thrombosis is only one of the possible associated clinical and neuroradiological features. The aim of this review is to address from a neurovascular point of view the multifaceted range of the arterial side of APS. A modern neurovascular approach was proposed, dividing the CNS involvement on the basis of the size of affected arteries, from large to small arteries, and corresponding clinical and neuroradiological issues. Both large-vessel and small-vessel involvement in APS were detailed, highlighting the limitations of the available literature in the attempt to derive some pathomechanisms. APS is a complex disease, and its neurological involvement appears multifaceted and not yet fully characterized, within and outside the diagnostic criteria. The involvement of intracranial large and small vessels appears poorly characterized, and the overlapping with the previously proposed inflammatory manifestations is consistent.

Background and Objectives: The focus on mild cognitive dysfunction in adults is of great interest, given the risk of worsening and conversion to dementia. Cognitive dysfunctions are characterized by a decrease in the weight and volume of the brain, due to cortical atrophy, with a widening of the grooves and flattening of the convolutions. Brain atrophy that mainly involves the hippocampus is related to the progression of cognitive impairment and the conversion from mild cognitive dysfunction to dementia. Currently, there is no treatment for MCI. Results from a trial on Alzheimer’s disease (ASCOMALVA trial) suggest that a sustained cholinergic challenge can slow the progression of brain atrophy typical of Alzheimer’s disease associated with vascular damage. This study intends to evaluate the efficacy of choline alphoscerate in patients with mild cognitive impairment (MCI) and associated vascular damage, in stabilizing and/or slowing brain atrophy typical of adult-onset cognitive dysfunction, and in improving and/or slowing the progression of cognitive and behavioral symptoms associated with MCI. Materials and Methods: This randomized controlled trial will recruit 60 patients that will be evaluated and randomized in a 1:1 ratio to receive choline alphoscerate (1200 mg/day) or placebo, for 12 months. Analyses will be carried out using SPSS vesion No 26 the Statistician in charge of this study, with the statistical significance level chosen as 0.05. Discussion: This trial may provide evidence about the efficacy of treatment with the cholinergic precursor choline alphoscerate in patients with mild cognitive dysfunction. The results of this study will be published in peer-reviewed journals. Registration: EudraCT number: 2020-000576-38

We report a study on the hydrogen bonding mechanisms of three aliphatic alcohols (2-propanol, methanol, and ethanol) and one diol (ethylene glycol) in water solution using a time-domain ellipsometer in the THz region. The dielectric response of the pure liquids is nicely modeled by the generalized Debye–Lorentz equation. For binary mixtures, we analyze the data using a modified effective Debye model, which considers H-bond rupture and reformation dynamics and the motion of the alkyl chains and of the OH groups. We focus on the properties of the water-rich region, finding anomalous behavior in the absorption properties at very low solute molar concentrations. These results, first observed in the THz region, are in line with previous findings from different experiments and can be explained by taking into account the amphiphilic nature of the alcohol molecules.

Francesca Benevento,1 Anna Pecorelli,2 Horia Stefanescu,3 Zeno Sparchez,3 Ranka Vukotic,1,4 Irene Pettinari,2 Crina-Anca Grigoras,3 Francesco Tovoli,1,5 Federico Ravaioli,1 Bernardo Stefanini,1 Pietro Andreone,6 Fabio Piscaglia1,5 1Department of Medicine and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy; 2Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 3Gastroenterology Department, Liver Unit & Ultrasound Laboratory, Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca, Romania; 4Medicina Interna 4, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; 5Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 6Divisione di Medicina Interna a Indirizzo Metabolico-Nutrizionale, Azienda Ospedaliero-Universitaria di Modena, Modena, ItalyCorrespondence: Fabio Piscaglia, Email Fabio.piscaglia@unibo.itBackground: Malignancies are generally considered a risk factor for deep vein thrombosis and may hamper the recanalisation of thrombosed veins.Aim: We investigate whether the natural course and response to anticoagulant treatment of bland portal vein thrombosis (PVT) in patients with cirrhosis complicated by hepatocellular carcinoma (HCC) differ from those without HCC.Methods: Retrospective study in two hepatology referral centres, in Italy and Romania where patients with a diagnosis of PVT on cirrhosis and follow-up of at least 3 months with repeated imaging were included.Results: A total of 162 patients with PVT and matching inclusion and exclusion criteria were identified: 30 with HCC were compared to 132 without HCC. Etiologies, Child-Pugh Score (7 vs 7) and MELD scores (11 vs 12, p=0.3679) did not differ. Anticoagulation was administered to 43% HCC vs 42% nonHCC. The extension of PVT in the main portal trunk was similar: partial/total involvement was 73.3/6.7% in HCC vs 67.4/6.1% in nonHCC, p=0.760. The remainder had intrahepatic PVT. The recanalization rate was 61.5% and 60.7% in HCC/nonHCC in anticoagulated patients (p=1). Overall PVT recanalisation, including treated and untreated patients, was observed in 30% of HCC vs 37.9% of nonHCC, p=0.530. Major bleeding incidence was almost identical (3.3% vs 3.8%, p=1). Progression of PVT after stopping anticoagulation did not differ (10% vs 15.9%, respectively, HCC/nHCC, p=0.109).Conclusion: The course of bland non-malignant PVT in cirrhosis is not affected by the presence of active HCC. Treatment with anticoagulation in patients with active HCC is safe and as effective as in nonHCC patients, this can potentially allow us to use otherwise contraindicated therapies (ie TACE) if a complete recanalization is achieved with anticoagulation.Keywords: LC, liver cirrhosis, HCC, hepatocellular carcinoma, PVT, portal vein thrombosis

Abstract Invasion dynamics are determined, among other aspects, by the spatial behaviour of invasive populations. The invasive toad Duttaphrynus melanostictus is spreading inland from the eastern coast of Madagascar, causing considerable ecological impacts. Understanding the basic factors determining the spread dynamics can inform management strategies and provide insights into spatial evolutionary processes. We radio-tracked 91 adult toads in three localities along the invasion gradient to determine whether spatial sorting of dispersive phenotypes is occurring, and investigate intrinsic and extrinsic determinants of spatial behaviour. Overall, toads in our study appeared as habitat generalists, and their sheltering behaviour was tied to water proximity, with toads changing shelter more frequently closer to waterbodies. Toads showed low displacement rates (mean = 4.12 m/day) and quite a philopatric behaviour but were able to perform daily movements of over 50 m. We did not detect any spatial sorting of dispersal-relevant traits nor sex- or size-biased dispersal. Our results suggest that toads are more likely to expand their range during the wet season, and that the range expansion is probably dominated by short-distance dispersal at this stage of the invasion, although a future increase in invasion speed is expected, due to the capacity for long-distance movements of this species.

Purpose A direct aspiration, first pass technique (ADAPT) has been introduced as a rapid and safe thrombectomy strategy in patients with intracranial large vessel occlusion (LVO). The aim of the study is to determine the technical feasibility, safety, and functional outcome of ADAPT using the newly released large bore pHLO 0.072-inch aspiration catheter (AC; Phenox). Materials and Methods We performed a retrospective analysis of data collected prospectively (October 2019–November 2021) from 2 comprehensive stroke centers. Accessibility of the thrombus, vascular recanalization, time to recanalization, and procedure-related complications were evaluated. National Institutes of Health stroke scale scores at presentation and discharge and the modified Rankin scale (mRS) score at 90 days post-procedure were recorded. Results Twenty-five patients (14 female, 11 male) with occlusions of the anterior circulation were treated. In 84% of cases, ADAPT led to successful recanalization with a median procedure time of 28 minutes. In the remaining cases, successful recanalization required (to a total of 96%; modified thrombolysis in cerebral infarction score 2b/3) the use of stent retrievers. No AC-related complications were reported. Other complications included distal migration of the thrombus, requiring a stent-retriever, and symptomatic PH2 hemorrhage in 16% and 4%, respectively. After 3 months, 52% of the patients had mRS scores of 0–2 with an overall mortality rate of 20%. Conclusion Results from our retrospective case series revealed that thrombectomy of LVOs with pHLO AC is safe and effective in cases of large-vessel ischemic stroke. Rates of complete or near-complete recanalization after the first pass with this method might be used as a new benchmark in future trials.

Liver transplantation represents a chief therapeutic approach for acute liver failure, end-stage liver disease and hepatocellular carcinoma. Despite witnessing advancements in short- and medium-term survival over recent decades, attributed to refinements in surgical techniques and immunosuppressive protocols, long-term mortality remains impervious to modification. Notably, cardiovascular disease emerges as a predominant cause of mortality among liver transplant recipients. This trend is accentuated by the increasing prominence of non-alcoholic steatohepatitis-related cirrhosis as an indication for liver transplantation. Moreover, the administration of immunosuppressive agents is intricately linked to the degradation of the metabolic profile in liver transplant recipients, thereby contributing to the initiation or exacerbation of cardiovascular risk factors, such as hypertension, diabetes, and dyslipidaemia. In addition, the post-liver transplantation period is marked by a decline in lifestyle quality and a failure to acknowledge the psychological distress experienced by patients throughout the transplant process. These factors can precipitate a deterioration in the patient’s metabolic profile, exacerbated by suboptimal therapeutic compliance. This narrative review aims to comprehensively address the principal metabolic disorders intricately associated with liver transplantation.

Islet transplantation represents a therapeutic option for type 1 diabetes (T1D). Long-term viability of transplanted islets requires improvement. Mesenchymal stromal cells (MSCs) have been proposed as adjuvants for islet transplantation facilitating grafting and functionality. Stem cell aggregation provides physiological interactions between cells and enhances the in situ concentration of modulators of inflammation and immunity. We established a hanging-drop culture of adult human skin fibroblast-like cells as spheroids, and skin spheroid-derived cells (SphCs) were characterized. We assessed the potential of SphCs in improving islet functionality by cotransplantation with a marginal mass of allogeneic islets in an experimental diabetic mouse model and characterized the secretome of SphCs by mass spectrometry-based proteomics. SphCs were characterized as multipotent progenitors and their coculture with anti-CD3 stimulated mouse splenocytes decreased CD4+ T cell proliferation with skewed cytokine secretion through an increase in the Th2/Th1 ratio profile. SphCs-conditioned media attenuated apoptosis of islets induced by cytokine challenge in vitro and importantly, intratesticular SphCs administration did not show tumorigenicity in immune-deficient mice. Moreover, SphCs improved glycemic control when cotransplanted with a marginal mass of allogeneic islets in a diabetic mouse model without pharmacological immunosuppression. SphCs' protein secretome differed from its paired skin fibroblast-like counterpart in containing 70% of up- and downregulated proteins and biological processes that overall positively influenced islets such as cytoprotection, cellular stress, metabolism, and survival. In summary, SphCs improved the performance of transplanted allogeneic islets in an experimental T1D model, without pharmacological immunosuppression. Future research is warranted to identify SphCs-secreted factors responsible for islets' endurance.

Background & aimsPrimary sclerosing cholangitis (PSC) is a rare, cholestatic liver disease with no currently approved therapies. Obeticholic acid (OCA) is a potent farnesoid X receptor (FXR) agonist approved for the treatment of primary biliary cholangitis. We investigated the efficacy and safety of OCA in patients with PSC.MethodsAESOP was a phase II, randomized, double-blind, placebo-controlled, dose-finding study. Eligible patients were 18 to 75 years of age with a diagnosis of PSC and serum alkaline phosphatase (ALP) ≥2× the upper limit of normal (ULN) and total bilirubin