The aim of this study was to synthesize a quinoline-based MRI contrast agent, Gd-DOTA-FAPI04, and assess its capacity for targeting fibroblast activation protein (FAP)-positive tumors in vivo. Gd-DOTA-FAPI04 was synthesized by attaching a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) complex of gadolinium(III) to FAP inhibitor FAPI04. The longitudinal relaxation time (T1) of the contrast agent was measured using a Siemens Prisma 3.0T MR system, and the CCK-8 assay was performed to evaluate its potential cytotoxicity. Male nude mice bearing tumors grown from FAP-expressing fibrosarcoma cells were divided into experimental (n = 4) and control (n = 4) groups, and T1-weighted image enhancement was measured at different times (0, 10, 30, 60, 90, and 120 min) postinjection of Gd-DOTA-FAPI04. The control group received an additional preinjection of excess FAPI04. FAP expression in tumor tissue was investigated by using immunohistochemistry with an anti-FAP antibody. The longitudinal relaxivities of gadodiamide and Gd-DOTA-FAPI04 were measured to be 3.734 mM-1 s-1 and 5.323 mM-1 s-1, respectively. The CCK-8 assay demonstrated that Gd-DOTA-FAPI04 has minimal toxicity to cultured human fibrosarcoma cells. In vivo MRI showed that peak accumulation of Gd-DOTA-FAPI04 in FAP-expressing tumors occurred 1 h postinjection and could be blocked by preinjection of excess FAPI04. Immunohistochemical analysis of harvested tumor tissue supported the above findings. Gd-DOTA-FAPI04 is a promising contrast agent for in vivo imaging of FAP.

Portal cavernoma thrombosis is a complication of portal cavernoma. We describe the case of a 74-year-old patient who presented to the emergency department with abdominal pain. The computed tomography scan showed a mass from the head of the pancreas to the hepatic hilum not enhanced after injection of iodinated contrast. There was no dilatation of the bile ducts. Abdominal magnetic resonance ruled out a tumour and confirmed a portal cavernoma thrombosis. In 50 % of cases the etiology of the portal cavernoma is unknown. It is often asymptomatic. It may be discovered in case of complications of portal hypertension. In rare cases the portal cavernoma can compress the bile ducts. To our knowledge, portal cavernoma thrombosis has only been described in one article. It is important to search for a thrombophilic disorder when such a complication is found. We share this case report in order to raise awareness in the medical community about this rare complication.
La thrombose de cavernome portal est une complication du cavernome porte. Nous décrivons le cas d’un patient de 74 ans qui s’est présenté aux urgences pour des douleurs abdominales. La tomodensitométrie montrait un syndrome de masse de la tête du pancréas jusqu’au hile hépatique non rehaussé après injection de produit de contraste iodé. Il n’y avait pas de dilatation des voies biliaires. Une imagerie par résonance magnétique abdominale a permis d’infirmer l’hypothèse d’une masse tumorale et d’affirmer une thrombose du cavernome porte. Dans 50 % des cas, l’étiologie du cavernome portal est inconnue. Il est souvent asymptomatique. Il peut être découvert en cas de complications à la suite d’une hypertension portale. Dans de rares cas, le cavernome portal peut comprimer les voies biliaires. À notre connaissance, la thrombose de cavernome portal n’a été décrite que dans un seul article. Il est important de rechercher un désordre thrombophilique quand une telle complication est retrouvée. Nous partageons ce cas clinique afin de sensibiliser la communauté médicale à cette rare complication.

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BACKGROUND: Immune thrombocytopenia (ITP) is a prevalent autoimmune bleeding disorder, with the primary objective of treatment being the prevention of bleeding. Clinical investigations have indicated that individuals with ITP face an elevated risk of thrombosis, and the occurrence of thromboembolic events in ITP patients can be attributed to a multitude of factors. However, establishing a definitive causal relationship between ITP and thrombosis remains challenging.
METHODS: A two-sample Mendelian randomization (MR) study utilizing summary data from FinnGen consortium and UK Biobank was undertaken to investigate the causal association between ITP and thrombosis. The primary analysis employed the inverse-variance weighted (IVW) method, while supplementary analyses were conducted using the MR-Egger, weighted median, and MR-PRESSO approaches.
RESULTS: Based on IVW method, there was a statistically significant but small positive correlation between ITP and thrombosis. Specifically, ITP patients exhibited a suggestive positive correlation with myocardial infarction and deep-vein thrombosis. However, our investigation did not identify any causal relationship between ITP and cerebral infarction, arterial embolism, other arterial embolisms, pulmonary embolism, thrombophlebitis, or portal vein thrombosis. Sensitivity analyses further confirmed the accuracy and robustness of these findings.
CONCLUSIONS: This study presents empirical support for the causal relationship between ITP and thrombosis. It is important to note that a diminished platelet count does not serve as a preventive measure against thrombus formation. Consequently, when managing a newly diagnosed ITP patient, clinicians need to be aware that there is a slight elevation in the risk of thrombosis during treatment.

BACKGROUND: Negative emotions and insomnia (NEI) can lead to inflammation, which is a characteristic of sepsis. However, the interaction among NEI and sepsis has not yet been proven. Therefore, Mendelian mediation was used to explore this relationship in this study.
METHODS: The genetic correlation NEI and sepsis was assessed by via linkage disequilibrium scores (LDSC). A two-sample Mendelian randomization (MR) study design was performed to examine the causal association between NEI and sepsis using the inverse variance weighted (IVW) method. The reliability of the results was estimated by weighted median and MR-Egger methods, but heterogeneity was evaluated via Radial and Cochran\'s Q tests. Biases in gene polymorphisms were checked by MR-Egger regression and MR-PRESSO. Mendelian mediation analyses were applied to quantify the intermediary effect and proportional contribution.
RESULTS: A genetic link between sepsis and depression was determined via LDSC analysis. The relationship between depression and sepsis was revealed through MR analysis [odds ratio (OR) = 1.21, 95 % confidence interval (CI) = 1.08-1.36, p = 1.07 × 10-3)]. The results were not influenced by heterogeneity or pleiotropy biases. Chitinase 3 Like 1 (CHI3L1) was a mediator with a mediation effect size of 0.12. The ratio of the intermediated effect to total effect was 10.31 %.
CONCLUSIONS: CHI3L1 is a key factor which mediates the interaction between NEI and sepsis.

Mitral regurgitation (MR) is a broadly diffuse valvular heart disease (VHD) with a significant impact on the healthcare system and patient prognosis. Transcatheter mitral valve interventions (TMVI) are now well-established techniques included in the therapeutic armamentarium for managing patients with mitral regurgitation, either primary or functional MR. Even if the guidelines give indications regarding the correct management of this VHD, the wide heterogeneity of patients\' clinical backgrounds and valvular and heart anatomies make each patient a unique case, in which the appropriate device\'s selection requires a multimodal imaging evaluation and a multidisciplinary discussion. Proper pre-procedural evaluation plays a pivotal role in judging the feasibility of TMVI, while a cooperative work between imagers and interventionalist is also crucial for procedural success. This manuscript aims to provide an exhaustive overview of the main parameters that need to be evaluated for appropriate device selection, pre-procedural planning, intra-procedural guidance and post-operative assessment in the setting of TMVI. In addition, it tries to give some insights about future perspectives for structural cardiovascular imaging.

The UK Biobank (UKB) has the largest adult brain imaging dataset, which encompasses over 40,000 participants. A significant number of Mendelian randomization (MR) studies based on UKB neuroimaging data have been published to validate potential causal relationships identified in observational studies. Relevant articles published before December 2023 were identified following the PRISMA protocol. Included studies (n = 34) revealed that there were causal relationships between various lifestyles, diseases, biomarkers, and brain image-derived phenotypes (BIDPs). In terms of lifestyle habits and environmental factors, there were causal relationships between alcohol consumption, tea intake, coffee consumption, smoking, educational attainment, and certain BIDPs. Additionally, some BIDPs could serve as mediators between leisure/physical inactivity and major depressive disorder. Regarding diseases, BIDPs have been found to have causal relationships not only with Alzheimer\'s disease, stroke, psychiatric disorders, and migraine, but also with cardiovascular diseases, diabetes, poor oral health, osteoporosis, and ankle sprain. In addition, there were causal relationships between certain biological markers and BIDPs, such as blood pressure, LDL-C, IL-6, telomere length, and more.

UNASSIGNED: The relationship between gut microbiota and hematologic malignancies has attracted considerable attention. As research progresses, it has become increasingly clear that the composition of gut microbiota may influence the onset and progression of hematologic malignancies. However, our understanding of this association remains limited.
UNASSIGNED: In our study, we classified gut microbiota into five groups based on information at the phylum, class, order, family, and genus levels. Subsequently, we obtained data related to common hematologic malignancies from the IEU Open GWAS project. We then employed a bidirectional Mendelian Randomization (MR) approach to determine whether there is a causal relationship between gut microbiota and hematologic malignancies. Additionally, we conducted bidirectional MR analyses to ascertain the directionality of this causal relationship.
UNASSIGNED: Through forward and reverse MR analyses, we found the risk of lymphoid leukemia was significantly associated with the abundance of phylum Cyanobacteria, order Methanobacteriales, class Methanobacteria, family Peptococcaceae, family Methanobacteriaceae, and genera Lachnospiraceae UCG010, Methanobrevibacter, Eubacterium brachy group, and Butyrivibrio. The risk of myeloid leukemia was significantly associated with the abundance of phylum Actinobacteria, phylum Firmicutes, order Bifidobacteriales, order Clostridiales, class Actinobacteria, class Gammaproteobacteria, class Clostridia, family Bifidobacteriaceae, and genera Fusicatenibacter, Eubacterium hallii group, Blautia, Collinsella, Ruminococcus gauvreauii group, and Bifidobacterium. The risk of Hodgkin lymphoma was significantly associated with the abundance of family Clostridiales vadinBB60 group, genus Peptococcus, and genus Ruminococcaceae UCG010. The risk of malignant plasma cell tumor was significantly associated with the abundance of genera Romboutsia and Eubacterium rectale group. The risk of diffuse large B-cell lymphoma was significantly associated with the abundance of genera Erysipelatoclostridium and Eubacterium coprostanoligenes group. The risk of mature T/NK cell lymphomas was significantly associated with the abundance of phylum Verrucomicrobia, genus Ruminococcaceae UCG013, genus Lachnoclostridium, and genus Eubacterium rectale group. Lastly, the risk of myeloproliferative neoplasms was significantly associated with the abundance of genus Coprococcus 3 and Eubacterium hallii group.
UNASSIGNED: Our study provided new evidence for the causal relationship between gut microbiota and hematologic malignancies, offering novel insights and approaches for the prevention and treatment of these tumors.

UNASSIGNED: The prevalence of pulmonary tuberculosis (PTB) as an infectious disease continues to contribute significantly to global mortality. According to recent studies, the gut microbiota of PTB patients and healthy controls (HCs) show significant disparities. However, the causal relationship between them has yet to be elucidated.
UNASSIGNED: We conducted a study using Mendelian Randomization (MR) to explore the potential causal link between gut microbiota and pulmonary tuberculosis (PTB). The summary statistics of the gut microbiota were acquired from the MiBioGen consortium, while data on PTB were sourced from pheweb.jp. A range of statistical methodologies were employed to evaluate causality, encompassing inverse variance weighting (IVW), MR-Egger, weighted median (WM), weighted model, and simple model. We utilized instrumental variables (IVs) that have a direct causal relationship with PTB to annotate SNPs, aiming to discover the genes harboring these genetic variants and uncover potential associations between host genes and the microbiome in patients with PTB.
UNASSIGNED: Among the 196 bacterial traits in the gut microbiome, we have identified a total of three microbiomes that exhibit a significant association with PTB. The occurrence of Dorea (P = 0.0458, FDR-adjusted P = 0.0458) and Parasutterella (P = 0.0056, FDR-adjusted P = 0.0168) was linked to an elevated risk of PTB, while the presence of Lachnoclostridium (P = 0.0347, FDR-adjusted P = 0.0520) demonstrated a protective effect against PTB. Our reverse Two-Sample Mendelian Randomization (TSMR) analysis did not yield any evidence supporting the hypothesis of reverse causality from PTB to alterations in the intestinal flora.
UNASSIGNED: We have established a connection between the gut microbiota and PTB through gene prediction analysis, supporting the use of gut microecological therapy in managing PTB and paving the way for further understanding of how gut microbiota contributes to PTB\'s development.

This case report explores the complexities involved in the diagnosis and management of asymptomatic mitral regurgitation (MR) in a 64-year-old male presenting with an incidental systolic murmur. Torrential MR with flail mitral valve (MV) segments was identified through comprehensive imaging and clinical evaluation, including echocardiography and catheterization. The discussion highlights the nuances of surgical timing, emphasizing the importance of tailored approaches based on left ventricular (LV) function and dilation. This report sheds light on the evolving landscape of managing asymptomatic MR, underscoring the need for balancing surveillance with proactive intervention to optimize patient outcomes.