OBJECTIVES: Despite increasing interest, prospective data on the use of degradable starch microsphere-transarterial chemoembolization (DSM-TACE) in the management of patients with unresectable HCC are still scarce. The objective of the HepaStar study was to collect prospective safety and effectiveness data in a prospective multicenter observational study. MATERIALS AND METHODS: Between January 2017 and December 2022, consecutive participants with unresectable or recurrent HCC treated with DSM-TACE as standard of care at 6 participating centers in Europe were enrolled. Tumor response was evaluated according to the mRECIST criteria. Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were assessed by using Kaplan-Meier analysis and Common Terminology Criteria for Adverse Events, version 5. Liver function deterioration was assessed by monitoring changes in liver blood tests during the follow-up. RESULTS: Seventy-nine participants (median age, 69 years (IQR, 51-87 years); 67 men (85%)) were enrolled and treated. The median follow-up time was 18 months (IQR 9.5-38.0 months). The estimated median OS and PFS for the entire cohort was 32 months (CI, 95% 21-NaN) and 9 months (CI, 95% 7-NaN), respectively. Eleven (13.9%) participants experienced at least one grade 3 or 4 AE. The most frequent grade 3-4 AE was elevated bilirubin (2.2%, 5 of 79). Deterioration of bilirubin, AST, ALT, and albumin were observed in 24.1%, 23.7%, 19%, and 24% of participants, respectively. CONCLUSION: DSM-TACE achieves promising survival in patients with unresectable or recurrent HCC. This technique shows a favorable safety profile both in terms of treatment-related AEs and liver function deterioration. KEY POINTS: Question Although degradable starch microspheres transarterial chemoembolization is widely used in clinical practice across Europe, prospective data on its application in hepatocellular carcinoma patients remains limited. Findings Degradable starch microspheres transarterial chemoembolization results in promising survival rates, good tumor response rates, and low rates of treatment-related adverse events. Clinical relevance In patients with unresectable hepatocellular carcinoma, degradable starch microspheres transarterial chemoembolization represents a safe and effective alternative to more well-established chemoembolization techniques like conventional transarterial chemoembolization and drug-eluting beads transarterial chemoembolization.

• MeSH
• Chemoembolization, Therapeutic * methods   MeSH
• Carcinoma, Hepatocellular * therapy   mortality   MeSH
• Middle Aged MeSH
• Humans MeSH
• Microspheres MeSH
• Liver Neoplasms * therapy   mortality   MeSH
• Prospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Starch * administration & dosage   MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Observational Study MeSH

BACKGROUND: A number of recent studies have shown that the intestinal microbiome, part of the brain-gut axis, is implicated in the pathophysiology of multiple sclerosis. An essential part of this axis, is the intestinal barrier and gastrointestinal disorders with intestinal barrier dysregulation appear to be linked to CNS demyelination, and hence involved in the etiopathogenesis of multiple sclerosis (MS). OBJECTIVE: The aim of this study was to evaluate the integrity of the intestinal barrier in patients with clinically definite multiple sclerosis (CDMS) and clinically isolated syndrome (CIS) using two serum biomarkers, claudin-3 (CLDN3), a component of tight epithelial junctions, and intestinal fatty acid binding protein (I-FABP), a cytosolic protein in enterocytes. METHODS: Serum levels of CLDN3 in 37 MS patients and 22 controls, and serum levels of I-FABP in 46 MS patients and 51 controls were measured using commercial ELISA kits. Complete laboratory tests excluded the presence of gluten-related disorders in all subjects. Thirty MS patients received either disease-modifying drugs (DMD), immunosuppression (IS) or corticosteroid treatment. RESULTS: CLDN3 levels were only significantly higher in the MS patients treated with DMD or IS compared to the control group (P=0.006). There were no differences in I-FABP serum levels between the groups. Serum CLDN3 levels did not correlate with serum I-FABP levels in CDMS, in CIS patients or controls. CONCLUSIONS: In multiple sclerosis patients, the intestinal epithelium may be impaired with increased permeability, but without significant enterocyte damage characterized by intracellular protein leakage. Based on our data, CLDN3 serum levels appear to assess intestinal dysfunction in MS patients but mainly in treated ones.

• MeSH
• Biomarkers * blood   MeSH
• Claudin-3 * metabolism   MeSH
• Adult MeSH
• Intestinal Barrier Function MeSH
• Middle Aged MeSH
• Humans MeSH
• Permeability * MeSH
• Fatty Acid-Binding Proteins * blood   MeSH
• Multiple Sclerosis * physiopathology   metabolism   blood   MeSH
• Intestinal Mucosa metabolism   MeSH
• Case-Control Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Alveolární echinokokóza (AE) je vzácné, ale závažné parazitární onemocnění jater, které často napodobuje maligní ložiska. V této kazuistice prezentujeme případ 76letého pacienta, u něhož byla AE diagnostikována náhodně při vyšetření pro renální insuficienci. Ultrazvukové vyšetření odhalilo mnohočetná hyperechogenní ložiska v játrech. Následné CT a MR jater zobrazily mnohočetná ložiska nepravidelných okrajů bez typické vaskularizace, největší o velikosti 71 × 38 mm. Laboratorní výsledky ukázaly zvýšené jaterní enzymy, CRP a renální insuficienci. Core cut biopsie jater potvrdila přítomnost pseudocystických struktur. Vzorky byly následně zaslány do Národní referenční laboratoře pro tkáňové helmintózy, která diagnózu AE potvrdila. Sérologické vyšetření bylo provedeno až po bioptickém vyšetření a potvrdilo přítomnost protilátek proti Echinococcus multilocularis. Pacient byl odeslán do infekční ambulance, kde byla zahájena léčba albendazolem v dávce 800 mg denně. Po rehydrataci a úpravě léčby došlo ke stabilizaci renálních funkcí a při kontrolních zobrazovacích vyšetřeních byl nález stacionární. Tento případ zdůrazňuje nutnost zařazení AE do diferenciální diagnostiky ložiskových procesů jater, zejména u pacientů bez onkologické anamnézy.

Alveolar echinococcosis (AE) is a rare but serious parasitic liver disease that often mimics malignant lesions. We present the case of a 76-year-old patient in whom AE was incidentally diagnosed during examination for renal insufficiency. Abdominal ultrasound revealed multiple hyperechogenic liver lesions. Subsequent MRI showed multiple irregularly bordered lesions without typical vascularization, the largest measuring 71 × 38 mm. Laboratory tests revealed elevated liver enzymes, CRP, and renal insufficiency. A core-cut liver biopsy confirmed the presence of pseudocystic structures. Samples were sent to the National Reference Laboratory for Tissue Helminthiases, which confirmed the diagnosis of AE. Serological testing was performed after the biopsy confirming the presence of antibodies against Echinococcus multilocularis. The patient was referred to an infectious disease clinic, where treatment with albendazole at a dose of 800 mg daily was initiated. After rehydration and adjustment of therapy, renal function stabilized, and follow-up imaging showed stable findings. This case highlights the need to include AE in the differential diagnosis of hepatic lesions, particularly in patients without an oncological history.

• MeSH
• Albendazole pharmacology   therapeutic use   MeSH
• Biopsy MeSH
• Diagnostic Imaging methods   MeSH
• Echinococcosis, Hepatic * diagnosis   drug therapy   MeSH
• Liver diagnostic imaging   pathology   MeSH
• Humans MeSH
• Aged MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Publication type
• Case Reports MeSH

• Keywords
• MASLD,
• MeSH
• Liver Function Tests methods   MeSH
• Liver metabolism   pathology   MeSH
• Case Reports as Topic MeSH
• Ursodeoxycholic Acid pharmacology   therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Non-alcoholic Fatty Liver Disease * drug therapy   classification   physiopathology   MeSH
• Fatty Liver diagnosis   etiology   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Review MeSH

BACKGROUND: Marathon training and running have many beneficial effects on human health and physical fitness; however, they also pose risks. To date, no comprehensive review regarding both the benefits and risks of marathon running on different organ systems has been published. MAIN BODY: The aim of this review was to provide a comprehensive review of the benefits and risks of marathon training and racing on different organ systems. A predefined search strategy including keywords (e.g., marathon, cardiovascular system, etc.) and free text search was used. Articles covering running regardless of sex, age, performance level, and event type (e.g., road races, mountain marathons) were considered, whereas articles examining only cycling, triathlon, stress-tests or other sports were excluded. In total, we found 1021 articles in PubMed, Scopus, and Google Scholar, of which 329 studies were included in this review. Overall, marathon training offers several benefits for different organ systems and reduces all-cause mortality. As such, it improves cardiovascular risk factors, leads to favorable cardiac adaptations, enhances lung function, and improves quality of life in chronic kidney disease patients. It also enhances gastrointestinal mobility and reduces the risk of specific tumors such as colorectal cancer and hepatocellular carcinoma. Marathon training enhances bone health and skeletal muscle metabolism. It further positively affects hematopoiesis and cytotoxic abilities of natural killer cells, and may act neuroprotective on a long-term basis. After a marathon, changes in biomarkers suggesting pathological events in certain organ systems such as cardiovascular, renal, gastrointestinal, liver, hematological, immune, musculoskeletal, central nervous, and endocrine systems can often be observed. Mostly, these changes are limited to 1-3 days post-race and usually normalize within a week. Moreover, marathon running poses the risk of serious adverse events such as sudden cardiac death or acute liver failure. Concerning lung function, a decrease after a marathon race was observed. Acute kidney injury, as well as electrolyte imbalances, are relatively common amongst marathon finishers. Many runners complain of gastrointestinal symptoms during or after long-distance running. Many runners suffer from running-related musculoskeletal injuries often impairing performance. A marathon is often accompanied by an acute inflammatory response with transient immunosuppression, making runners susceptible to infections. Also, hormonal alterations such as increased cortisol levels or decreased testosterone levels immediately after a race are observed. Disturbances in sleep patterns are commonly found in marathon runners leading up to or directly after the race. CONCLUSION: All in all, marathon training is generally safe for human health and individual organ systems. Considering the high popularity of marathon running, these findings supply athletes, coaches, sports scientists, and sports medicine practitioners with practical applications. Further large-scale studies examining long-term effects on the cardiovascular, renal, and other system are needed.

• Publication type
• Journal Article MeSH
• Review MeSH

PURPOSE: This prospective pilot study aims to evaluate the capabilities of novel quantitative ultrasound (QUS) methods based on attenuation (Att.PLUS) and sound speed (SSp.PLUS) for detecting liver fat. PATIENTS AND METHODS: The study included 56 individuals with biopsy-proven steatosis (percutaneous liver biopsy) ranging from 0 % to 90 % of hepatocytes containing intracellular lipid vacuoles. Histopathology was considered reference standard. Abdominal QUS examinations were conducted using Att.PLUS and SSp.PLUS techniques on the Aixplorer MACH 30 system. Comparative assessments were made using the results of liver biopsy and magnetic resonance spectroscopy (MRS) together with magnetic resonance imaging proton density fat fraction (MRI-PDFF). MR examinations were performed on the Siemens VIDA 3 T system. RESULTS: ROC analysis was conducted for two groups: (a) patients without steatosis (S0) versus those with steatosis (S1 + S2 + S3) yielded AUC values of 0.79 for Att.PLUS and 0.78 for SSp.PLUS, in contrast to an AUC > 0.95 for MRS and MRI-PDFF; and (b) patients without or with mild steatosis (S0 + S1) versus those with severe steatosis (S2 + S3), yielded AUC values of 0.93 for Att.PLUS and 0.89 for SSp.PLUS, in contrast to an AUC > 0.99 for MRS and MRI-PDFF. However, MR methods were superior in detecting liver fat content in obese patients and post-liver transplantation individuals. CONCLUSION: Both QUS parameters (Att.PLUS and SSp.PLUS) appear equivalent at differentiating S0 vs. (S1 + S2 + S3) patients, but the Att.PLUS parameter may be more effective at identifying advanced steatosis (S2 + S3). MR techniques outperformed QUS methods, making them more suitable for clinical studies.

• MeSH
• Biopsy MeSH
• Adult MeSH
• Liver diagnostic imaging   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Spectroscopy methods   MeSH
• Magnetic Resonance Imaging * methods   MeSH
• Pilot Projects MeSH
• Prospective Studies MeSH
• Reproducibility of Results MeSH
• Aged MeSH
• Sensitivity and Specificity MeSH
• Ultrasonography * methods   MeSH
• Fatty Liver * diagnostic imaging   pathology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH

PURPOSE: Patients with high-grade serous ovarian carcinoma (HGSOC) are virtually insensitive to immune checkpoint inhibitors (ICI) employed as standalone therapeutics, at least in part reflecting microenvironmental immunosuppression. Thus, conventional chemotherapeutics and targeted anticancer agents that not only mediate cytotoxic effects but also promote the recruitment of immune effector cells to the HGSOC microenvironment stand out as promising combinatorial partners for ICIs in this oncological indication. EXPERIMENTAL DESIGN: We harnessed a variety of transcriptomic, spatial, and functional assays to characterize the differential impact of neoadjuvant paclitaxel-carboplatin on the immunological configuration of paired primary and metastatic HGSOC biopsies as compared to neoadjuvant chemotherapy (NACT)-naïve HGSOC samples from five independent patient cohorts. RESULTS: We found NACT-driven endoplasmic reticulum stress and calreticulin exposure in metastatic HGSOC lesions culminates with the establishment of a dense immune infiltrate including follicular T cells (TFH cells), a prerequisite for mature tertiary lymphoid structure (TLS) formation. In this context, TLS maturation was associated with an increased intratumoral density of ICI-sensitive TCF1+PD1+ CD8+ T cells over their ICI-insensitive TIM-3+PD1+ counterparts. Consistent with this notion, chemotherapy coupled with a PD1-targeting ICI provided a significant survival benefit over either therapeutic approach in syngeneic models of HGSOC bearing high (but not low) tumor mutational burden. CONCLUSIONS: Altogether, our findings suggest that NACT promotes TLS formation and maturation in HGSOC lesions, de facto preserving an intratumoral ICI-sensitive T-cell phenotype. These observations emphasize the role of rational design, especially relative to the administration schedule, for clinical trials testing chemotherapy plus ICIs in patients with HGSOC. See related commentary by Bravo Melgar and Laoui, p. 10.

• MeSH
• CD8-Positive T-Lymphocytes * immunology   drug effects   MeSH
• Tertiary Lymphoid Structures * immunology   pathology   MeSH
• Hepatocyte Nuclear Factor 1-alpha * genetics   metabolism   MeSH
• Immune Checkpoint Inhibitors * therapeutic use   pharmacology   MeSH
• Carboplatin administration & dosage   pharmacology   therapeutic use   MeSH
• Humans MeSH
• Tumor Microenvironment * immunology   drug effects   MeSH
• Ovarian Neoplasms * drug therapy   immunology   pathology   MeSH
• Neoadjuvant Therapy methods   MeSH
• Paclitaxel administration & dosage   therapeutic use   pharmacology   MeSH
• Antineoplastic Combined Chemotherapy Protocols therapeutic use   pharmacology   MeSH
• Cystadenocarcinoma, Serous drug therapy   pathology   immunology   MeSH
• Endoplasmic Reticulum Stress drug effects   immunology   MeSH
• Lymphocytes, Tumor-Infiltrating immunology   drug effects   metabolism   MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Background and Objectives: Initial diagnosis of brest cancer (BC) is important for fate and prognosis of the diseases profile, we sought to identify the correlation between Midkine (MK) as a new biomarker with cancer antigen (CA)15-3, liver function test, renal function test, blood cells parameters in individuals with invasive ductal carcinoma.Methods: The serum MK and CA15-3 of all subjects were measured by the ELISA technique, Liver enzymes were measured by colourimetric methods and neutrophils, and lymphocytes were measured by an Electrical Impedance Cell Counting method (automated machine).Results: The results of the correlation among serum MK and other parameters in invasive ductal carcinoma of the breast showed a considerable positive correlation among MK and CA15-3 and measured white blood cells. Moreover, there were a weak correlation with Aspartate Aminotransferase (AST) and RBC, while there is no correlation between serum MK and other liver enzymes or blood parameters. Conclusion: The study results of the correlation between serum MK and other parameters in colorectal carcinoma patients show a significant positive correlation of MK with CA15-3 markers in invasive ductal carcinoma of the breast.

• MeSH
• Carcinoma, Ductal, Breast blood   MeSH
• Enzyme-Linked Immunosorbent Assay methods   MeSH
• Liver Function Tests MeSH
• Clinical Studies as Topic methods   MeSH
• Humans MeSH
• Lymphocytes metabolism   MeSH
• Midkine * analysis   blood   MeSH
• Biomarkers, Tumor * blood   MeSH
• Breast Neoplasms * diagnosis   blood   MeSH
• Neutrophils metabolism   MeSH
• Kidney Function Tests MeSH
• Check Tag
• Humans MeSH

Portosinusoidální vaskulární choroba (PSVD) je málo rozpoznávané onemocnění jater podmíněné postižením malých cév. Diagnóza je definována souborem klinických a/nebo histopatologických kritérií, absolutní podmínkou je vyloučení cirhózy jater biopsií. Klinicky se PSVD obvykle manifestuje komplikací portální hypertenze, ta ale nemusí byt vyjádřena u všech nemocných. V článku popisujeme případ 71letého pacienta se známou, hematologicky nevysvětlenou a dále neprošetřenou splenomegalií, který byl vyšetřen pro těžkou symptomatickou mikrocytární anemii, pravděpodobně sekundární k portální hypertenzi, byť bez deklarovaných krvácivých projevů. Za hospitalizace byla provedena ligace velkých rizikových varixů jícnu, jiný zdroj anemizace prokázán nebyl. U pacienta byla vyloučena pre- nebo posthepatální etiologie portální hypertenze, elastografie jater byla ve fyziologických hodnotách, jaterní testy byly vyjma marginální izolované elevace gama-glutamyltransferázy v normě, funkce jater byla intaktní. V jaterní biopsii byl nález kompatibilní s diagnózou PSVD. U pacienta nebylo rozpoznáno žádné z asociovaných onemocnění, rovněž neužíval rizikovou medikaci, léčba tudíž spočívala pouze v řešení komplikací portální hypertenze, ambulantně byla dokončena eradikace jícnových varixů. Při terapii perorálním preparátem železa došlo k normalizaci hemoglobinu, fyziologické hodnoty přetrvávají i měsíce po ukončení substituční léčby, jaterní funkce je nadále v normě.

Portosinusoidal vascular disease (PSVD) is a rarely recognized liver condition caused by the involvement of small hepatic vessels. The diagnosis is established based on a set of clinical and/or histopathological criteria, with the absolute requirement of excluding liver cirrhosis through biopsy. Clinically, PSVD often presents with complications related to portal hypertension, although not all patients exhibit these signs. This article discusses the case of a 71-year-old patient with known splenomegaly, which had not been fully investigated and lacked a hematological explanation. The patient was evaluated for severe symptomatic microcytic anemia, likely secondary to portal hypertension, despite the absence of overt bleeding symptoms. During hospitalization, ligation of large, high-risk esophageal varices was performed, and no other sources of anemia were identified. Pre- or post-hepatic causes of portal hypertension were ruled out. Liver elastography results were within normal ranges, and liver function tests were normal except for a marginal isolated elevation of gamma-glutamyltransferase. Liver function remained intact. Liver biopsy findings were consistent with a diagnosis of PSVD. The patient did not have any identifiable associated conditions and was not taking any medications known to pose a risk. Therefore, treatment was focused solely on managing the complications of portal hypertension. Outpatient follow-up included the eradication of esophageal varices. Treatment with oral iron supplements led to the normalization of hemoglobin levels, which remained stable for months after the discontinuation of therapy, and liver function tests continued to be normal.

• MeSH
• Antihypertensive Agents therapeutic use   MeSH
• Anemia, Hypochromic diagnosis   drug therapy   MeSH
• Hepatic Veno-Occlusive Disease * diagnosis   therapy   MeSH
• Carvedilol therapeutic use   MeSH
• Humans MeSH
• Hypertension, Portal * diagnosis   drug therapy   MeSH
• Aged MeSH
• Splenomegaly MeSH
• Iron therapeutic use   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Publication type
• Case Reports MeSH

Fibrosis contributes to tissue repair, but excessive fibrosis disrupts organ function. Alagille syndrome (ALGS, caused by mutations in JAGGED1) results in liver disease and characteristic fibrosis. Here, we show that Jag1Ndr/Ndr mice, a model for ALGS, recapitulate ALGS-like fibrosis. Single-cell RNA-seq and multi-color flow cytometry of the liver revealed immature hepatocytes and paradoxically low intrahepatic T cell infiltration despite cholestasis in Jag1Ndr/Ndr mice. Thymic and splenic regulatory T cells (Tregs) were enriched and Jag1Ndr/Ndr lymphocyte immune and fibrotic capacity was tested with adoptive transfer into Rag1-/- mice, challenged with dextran sulfate sodium (DSS) or bile duct ligation (BDL). Transplanted Jag1Ndr/Ndr lymphocytes were less inflammatory with fewer activated T cells than Jag1+/+ lymphocytes in response to DSS. Cholestasis induced by BDL in Rag1-/- mice with Jag1Ndr/Ndr lymphocytes resulted in periportal Treg accumulation and three-fold less periportal fibrosis than in Rag1-/- mice with Jag1+/+ lymphocytes. Finally, the Jag1Ndr/Ndr hepatocyte expression profile and Treg overrepresentation were corroborated in patients' liver samples. Jag1-dependent hepatic and immune defects thus interact to determine the fibrotic process in ALGS.

• MeSH
• Alagille Syndrome pathology   genetics   MeSH
• Cell Differentiation * MeSH
• Hepatocytes * metabolism   pathology   MeSH
• Liver Cirrhosis * pathology   genetics   MeSH
• Humans MeSH
• Disease Models, Animal MeSH
• Mice, Inbred C57BL MeSH
• Mice, Knockout MeSH
• Mice MeSH
• Jagged-1 Protein * metabolism   genetics   MeSH
• T-Lymphocytes, Regulatory immunology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH