OBJECTIVE: Although the incidence of isolated gastric varices type 1 (IGV1) bleeding is low, the condition is highly dangerous and associated with high mortality, making its treatment challenging. We aimed to compare the safety and efficacy of endoscopic clipping combined with cyanoacrylate injection (EC-CYA) vs. transjugular intrahepatic portosystemic shunt (TIPS) in treating IGV1.
METHODS: In a single-center, randomized controlled trial, patients with IGV1 bleeding were randomly assigned to the EC-CYA group or TIPS group. The primary end-points were gastric variceal rebleeding rates and technical success. Secondary end-points included cumulative nonbleeding rates, mortality, and complications.
RESULTS: A total of 156 patients between January 2019 and April 2023 were selected and randomly assigned to the EC-CYA group (n = 76) and TIPS group (n = 80). The technical success rate was 100% for both groups. The rebleeding rates were 14.5% in the EC-CYA group and 8.8% in the TIPS group, showing no significant difference (P = 0.263). Kaplan-Meier analysis revealed that the cumulative nonbleeding rates at 6, 12, 24, and 36 months for the two groups lacked statistical significance (P = 0.344). Similarly, cumulative survival rates at 12, 24, and 36 months for the two groups were not statistically significant (P = 0.916). The bleeding rates from other causes were 13.2% and 6.3% for the respective groups, showing no significant difference (P = 0.144). No instances of ectopic embolism were observed in either group. The incidence of hepatic encephalopathy (HE) in the TIPS group was statistically higher than that in the EC-CYA group (P = 0.001).
CONCLUSIONS: Both groups are effective in controlling IGV1 bleeding. Notably, EC-CYA did not result in ectopic embolism, and the incidence of HE was lower than that observed with TIPS.

OBJECTIVE: To report antegrade transvenous obliteration, with or without concurrent portosystemic shunt creation, for the treatment of hemorrhagic rectal varices.
METHODS: Eight patients, including five (62.5%) females and three (37.5%) males, with mean age of 55.8 ± 13.8 years (range: 30-70 years), underwent transjugular-approach antegrade transvenous obliteration of rectal varices, with or without portosystemic shunt creation. Demographic data, procedural details, technical success of variceal obliteration, clinical success, adverse events, and follow-up outcomes were retrospectively recorded. Clinical success was defined as resolution of rectal hemorrhage.
RESULTS: Portal venous access was achieved via a transjugular intrahepatic approach in all patients. The inferior mesenteric vein was selected, and foamy sclerosant (1:2:3 mixture by volume of ethiodized oil: sodium tetradecyl sulfate: air) was injected into the rectal varices with antegrade balloon occlusion in seven (87.5%) and without balloon occlusion in one (12.5%). Five of eight (62.5%) patients underwent concomitant transjugular intrahepatic portosystemic shunt (TIPS) creation (mean diameter 8.4 ± 0.9-mm) immediately following transvenous obliteration. Technical success of variceal obliteration was achieved in all patients. There were no immediate post-procedural adverse events. There were no reported occurrences of rectal ischemia, perforation, or stricture following obliteration. Two (40%) of the patients who underwent concomitant TIPS creation developed hepatic encephalopathy within 30 days of the procedure, which was medically managed. Clinical resolution of hemorrhage was achieved in all patients with no recurrent rectal variceal hemorrhage during mean follow-up of 666 ± 396 days (range: 14 - 1,224 days).
CONCLUSIONS: Transvenous obliteration, with or without concurrent TIPS creation, is feasible with promising results for the management of rectal variceal hemorrhage.

Sinusoidal obstruction syndrome (SOS) is a rare but potentially life-threatening complication, usually described in the setting of hematopoietic stem cell transplantation (HSCT). The very severe forms have a high mortality rate (>80%) and need fast recognition and urgent treatment. In this case report, we describe a unique and successful treatment strategy. We present a 27-year-old patient with newly diagnosed CD33+ acute myeloid leukemia (AML). She was treated with induction chemotherapy (7+3 regimen) and gemtuzumab ozogamicin (GO). In the absence of other major risk factors, she developed a very severe SOS with multiple organ failure. She was successfully treated with the urgent insertion of a transjugular intrahepatic portosystemic shunt (TIPS), defibrotide, and high-dose corticosteroids. This case of successful treatment for very severe SOS supports a combination strategy involving the immediate mechanical reduction of portal hypertension through TIPS and drug-mediated inhibition of microvascular thrombosis. Furthermore, this case shows the need for an improved prevention strategy, including the identification of additional risk factors and biomarkers.

BACKGROUND: During pseudoglandular stage of the human lung development the primitive bronchial buds are initially conformed by simple tubules lined by endoderm-derived epithelium surrounded by mesenchyme, which will progressively branch into airways and start to form distal epithelial saculles. For first time alveolar type II (AT2) pneumocytes appears. This study aims to characterize the genes and microRNAs involved in this differentiation process and decipher its role in the starting alveolar differentiation.
METHODS: Gene and microRNA profiling was performed in human embryonic lungs from 7 to 12 post conception weeks (pcw). Protein expression location of candidate genes were analyzed by immunofluorescense in embryonic lung tissue sections. mRNA/miRNA target pairs were identified using computational approaches and their expression was studied in purified epithelial/mesenchymal cell populations and in isolated tips and stalks from the bronchial tree. Additionally, silencing experiments in human embryonic lung mesenchymal cells and in human embryonic tip-derived lung organoids were performed, as well as organoid differentiation studies. AT2 cell markers were studied by qRT-PCR and by immunofluorescence. The TGFB-β phosphorylated pathways was analyzed with membrane protein arrays. Lung explants were cultured in air/liquid interface with/without peptides.
RESULTS: We identified 88 differentially expressed genes, including IGFBP3. Although IGFBP3 mRNA was detected in both epithelial and mesenchymal populations, the protein was restricted to the epithelium, indicating post-transcriptional regulation preventing IGFBP3 protein expression in the mesenchyme. MicroRNA profiling identified miR-34a as an IGFBP3 regulator. miR-34a was up-regulated in mesenchymal cells, and its silencing in human embryonic lung mesenchymal cells increased IGFBP3 levels. Additionally, IGFBP3 expression showed a marked downregulation from 7 to 12 pcw, suggesting its involvement in the differentiation process. The differentiation of human tip-derived lung embryonic organoids showed a drastic reduction in IGFBP3, supported by the scRNAseq data. IGFBP3 silencing in organoids activated an alveolar-like differentiation process characterized by stem cell markers downregulation and upregulation of AT2 markers. This process was mediated by TGFβ signalling inhibition and BMP pathway activation.
CONCLUSIONS: The IGFBP3/miR-34a axis restricts IGFBP3 expression in the embryonic undifferentiated lung epithelium, and the progressive downregulation of IGFBP3 during the pseudoglandular stage is required for alveolar differentiation.

OBJECTIVE: Salvage TIPS is indicated in patients with active endoscopically uncontrollable variceal bleeding. TIPS alone is not effective in management of gastric varices and BRTO requires favourable variceal anatomy. Concomittant placement of a TIPS stent with antegrade variceal embolisation leads to control of gastric variceal bleeding with no significant increase in portal pressure.
METHODS: A single centre retrospective observational study where patients with active uncontrollable gastric variceal bleeding were included in the study. Technical success of the procedure, 5-day rebleed, 6-weeks and 6-months survival as well as other additional outcomes were evaluated.
RESULTS: A total of 18 patients were included in the study. Technical success was 100% and significant non-target embolisation was seen in 0% patients. 6 week and 6 month survival rates were 66.67% with an overall survival of 108.786 days (censored at 180 days). 5 day rebleed rate was 11.1%. A significant difference in CTP score (p = 0.03), MELD Na score (p = 0.022), requirement of intubation (p = 0.038), hemoglobin levels (p = 0.042), hematocrit value (p = 0.018), PRBC infusion required prior to and after the procedure (p = 0.045, 0.044) and presence of refractory shock (p = 0.013) was observed between the survival and the mortality group. Post variceal bleeding hemoglobin levels, MAP and MELD-Na scores were significant predictors of mortality.
CONCLUSIONS: TIPS in adjunct to antegrade transvenous embolisation is a safe and effective modality for management of active uncontrolled gastric variceal bleeding in patients with variceal anatomy unfavourable for performing RTO.

To avoid recurrent variceal bleeding, transjugular intrahepatic portosystemic shunt (TIPS) in conjunction with variceal embolization is considered to be an effective strategy. However, due to changes in conditions and variations in the patient\'s state, individuals undergoing TIPS may face challenges and limitations during procedures. The transjugular technique and combined transsplenic portal venous recanalization (PVR) with TIPS were not effective in this case due to a blocked portal vein and a previous splenectomy. With an abdominal incision, we successfully punctured the mesenteric venous system and navigated the occluded segment of the portal vein through the mesenteric approach. TIPS was then performed under balloon guidance. This study aims to explore the management of risks and complications during surgical operations and propose multiple preoperative surgical techniques to improve the success rate of the procedure.

Colonic varicose veins are very rare and are usually discovered incidentally during colonoscopy or when complications occur, such as lower gastrointestinal (GI) bleeding. The primary cause of colonic varices is usually portal hypertension secondary to liver disease or very rarely due to pancreatic disease (e.g., pancreatic adenocarcinoma). Varicose veins secondary to cirrhosis are often seen in the upper GI tract but rarely in the lower GI tract. Here, we report a 54-year-old woman who presented with colonic varices due to decompensated alcoholic cirrhosis. The main intention of this case report was to raise awareness of the possibility of developing colonic varices from liver cirrhosis and to promptly identify and manage its side effects due to the major complication which is lower GI bleeding.

UNASSIGNED: Inflammatory and thrombotic biomarkers are simple prognostic indicators of adverse clinical outcomes in patients with ischemic stroke (IS). However, isolated assessment of inflammatory or thrombus biomarkers in patients with IS is limited in clinical practice.
UNASSIGNED: This study aimed to evaluate the predictive value of a novel, simplified thrombo-inflammatory prognostic score (TIPS) that combines both inflammatory and thrombus biomarkers in the early phase of IS and to identify high-risk patients at the time of admission. The study population comprised 915 patients with a primary diagnosis of IS in the emergency departments of five grade A tertiary hospitals in China.
UNASSIGNED: Patients were divided into two groups based on the modified Rankin Scale (mRS): <3 and ≥3. TIPS with a value of \"2\" indicates biomarkers for high inflammation and thrombosis, \"1\" represents a biomarker, and \"0\" signals the absence of a biomarker. Multivariate logistic regression analysis was employed to identify the association between TIPS and clinical outcomes. TIPS was an independent predictor of unfavorable functional outcomes and mortality. It had a superior predictive value for clinical outcomes compared to the National Institutes of Health Stroke Scale (NIHSS) (effect ratio, 37.5%), D-dimer (effect ratio, 12.5%), and neutrophil-to-lymphocyte ratio (effect ratio, 25%).
UNASSIGNED: The survival probability of TIPS with a score of 0 is twice as high as that of TIPS with a score of 2. The survival rate for TIPS with a score of 1 is one time higher than that for TIPS with a score of 2. The predictive value of TIPS for unfavorable functional outcomes is represented by an AUC of 0.653. TIPS is associated with an increased risk of death and unfavorable functional outcomes in patients with IS and may be a useful tool for identifying high-risk patients at the time of admission.

Transjugular intrahepatic portosystemic shunt (TIPS) has become essential in the treatment or prevention of portal hypertension-related complications. In the early 1990s, the primary indication was refractory bleeding. It is now proposed for the treatment of ascites for the prevention of bleeding and in patients with vascular diseases of the liver. Thus, there are a growing number of patients being treated with TIPS all over the world. The broadening of indications, the involvement of multiple stakeholders, the need for an accurate selection, the positioning in relation to transplantation and the lack of standardization in pre-therapeutic assessment, in the procedure itself and in the follow-up have led the board of the French Association for the Study of the Liver to establish recommendations.

OBJECTIVE: To assess the safety and effectiveness of percutaneous transsplenic access (PTSA) for portal vein (PV) interventions among patients with PV disease.
METHODS: Adult patients with PV disease were enrolled if they required percutaneous catheterization for PV angioplasty, embolization, thrombectomy, variceal embolization, or transjugular intrahepatic portosystemic shunt (TIPS) placement for a difficult TIPS or recanalization of a chronically occluded PV. The procedures were performed between January 2018 and January 2023. Patients were excluded if they had an active infection, had a chronically occluded splenic vein malignant infiltration of the needle tract, had undergone splenectomy, or were under age 18 years.
RESULTS: Thirty patients (15 women, 15 men) were enrolled. Catheterization of the PV through PTSA succeeded for 29 of 30 patients (96.7%). The main adverse effect recorded was flank pain in 5 of 30 cases (16.7%). No bleeding events from the spleen, splenic vein, or percutaneous access point were recorded. Two cases (6.7%) each of hepatic bleeding and rethrombosis of the PV were reported, and a change in hemoglobin levels (mean [SD], - 0.5 [1.4] g/dL) was documented in 14 cases (46.7%).
CONCLUSIONS: PTSA as an approach to accessing the PV is secure and achievable, with minimal risk of complications. Minimal to no bleeding is possible by using tract closure methods.