Illuminating protein space with a programmable generative model.

Three billion years of evolution has produced a tremendous diversity of protein molecules1, but the full potential of proteins is likely to be much greater. Accessing this potential has been challenging for both computation and experiments because the space of possible protein molecules is much larger than the space of those likely to have functions. Here we introduce Chroma, a generative model for proteins and protein complexes that can directly sample novel protein structures and sequences, and that can be conditioned to steer the generative process towards desired properties and functions. To enable this, we introduce a diffusion process that respects the conformational statistics of polymer ensembles, an efficient neural architecture for molecular systems that enables long-range reasoning with sub-quadratic scaling, layers for efficiently synthesizing three-dimensional structures of proteins from predicted inter-residue geometries and a general low-temperature sampling algorithm for diffusion models. Chroma achieves protein design as Bayesian inference under external constraints, which can involve symmetries, substructure, shape, semantics and even natural-language prompts. The experimental characterization of 310 proteins shows that sampling from Chroma results in proteins that are highly expressed, fold and have favourable biophysical properties. The crystal structures of two designed proteins exhibit atomistic agreement with Chroma samples (a backbone root-mean-square deviation of around 1.0 Å). With this unified approach to protein design, we hope to accelerate the programming of protein matter to benefit human health, materials science and synthetic biology.

Stereotactic ablative brachytherapy versus percutaneous microwave ablation for early-stage non-small cell lung cancer: a multicenter retrospective study.

BACKGROUND: To analyze the efficacy of stereotactic ablative brachytherapy (SABT) and percutaneous microwave ablation (MWA) for the treatment of early-stage non-small cell lung cancer (NSCLC). METHODS: Patients with early-stage (T1-T2aN0M0) NSCLC who underwent CT-guided SABT or MWA between October 2014 and March 2017 at four medical centers were retrospectively analyzed. Survival, treatment response, and procedure-related complications were assessed. RESULTS: A total of 83 patients were included in this study. The median follow-up time was 55.2 months (range 7.2-76.8 months). The 1-, 3-, and 5-year overall survival (OS) rates were 96.4%, 82.3%, and 68.4% for the SABT group (n = 28), and 96.4%, 79.7%, and 63.2% for MWA group (n = 55), respectively. The 1-, 3-, and 5-year disease-free survival (DFS) rates were 92.9%, 74.6%, and 54.1% for SABT, and 92.7%, 70.5%, and 50.5% for MWA, respectively. There were no significant differences between SABT and MWA in terms of OS (p = 0.631) or DFS (p = 0.836). The recurrence rate was also similar between the two groups (p = 0.809). No procedure-related deaths occurred. Pneumothorax was the most common adverse event in the two groups, with no significant difference. No radiation pneumonia was found in the SABT group. CONCLUSIONS: SABT provided similar efficacy to MWA for the treatment of stage I NSCLC. SABT may be a treatment option for unresectable early-stage NSCLC. However, future prospective randomized studies are required to verify these results.

Chimney Technique and Single-Branched Stent Graft for the Left Subclavian Artery Preservation During Zone 2 Thoracic Endovascular Aortic Repair for Type B Acute Aortic Syndromes.

PURPOSE: The purpose of this study was to evaluate the efficacy and safety of zone 2 thoracic endovascular aortic repair assisted by the chimney technique or single-branched stent graft for the preservation of the left subclavian artery, and summarize our single-center experience with the techniques. MATERIALS AND METHODS: From February 2017 to June 2020, 137 patients who underwent left subclavian artery revascularization during zone 2 thoracic endovascular aortic repair were enrolled. Patients had acute type B aortic dissection and penetrating aortic ulcer associated with intramural hematoma. The chimney technique was performed in 68 patients (group A), and single-branched stent graft was deployed in 69 patients (group B). All procedures were performed during the acute phase. Primary technical success, immediate postoperative endoleak, neurologic complications (stroke or spinal cord ischemia), 30-day mortality, 1-year technical success, all-cause mortality, patency of the left subclavian artery, and reintervention were analyzed. Comparing the occurrence of the Bird-Beak Configuration, defined as a gap between the aortic wall and the sent graft with stent protrusion into the aortic lumen more than 5 mm, was also performed. RESULTS: Primary technique success was achieved in 66 and 67 patients in groups A and B, respectively. The incidence of immediate postoperative endoleak, neurologic complications (stroke or spinal cord ischemia), and 30-day mortality were 5.9%, 1.5%, and 4.4% in group A, and 2.9%, 2.9%, and 2.9% in group B, respectively. During follow-up, the 1-year technical success rate was similar in both groups. All-cause mortality was similar in both groups (3.1% in group A and 4.5% in group B). The patency of the left subclavian artery was not significantly different between the 2 groups with 2 and 3 occlusions in groups A and B, respectively. The rate of reintervention was higher in group B (3.1% vs 1.6%, p=0.536), with a non-significant difference. Bird-Beak Configuration was more prominent in group B with the incidence of 59.42%. CONCLUSIONS: Acting as minimally invasive alternatives, both techniques are feasible for left subclavian artery preservation during zone 2 thoracic endovascular aortic repair for type B acute aortic syndromes with encouraging mid-term outcomes. Long-term follow-up is required to confirm these findings.

Learning pair potentials using differentiable simulations.

Learning pair interactions from experimental or simulation data is of great interest for molecular simulations. We propose a general stochastic method for learning pair interactions from data using differentiable simulations (DiffSim). DiffSim defines a loss function based on structural observables, such as the radial distribution function, through molecular dynamics (MD) simulations. The interaction potentials are then learned directly by stochastic gradient descent, using backpropagation to calculate the gradient of the structural loss metric with respect to the interaction potential through the MD simulation. This gradient-based method is flexible and can be configured to simulate and optimize multiple systems simultaneously. For example, it is possible to simultaneously learn potentials for different temperatures or for different compositions. We demonstrate the approach by recovering simple pair potentials, such as Lennard-Jones systems, from radial distribution functions. We find that DiffSim can be used to probe a wider functional space of pair potentials compared with traditional methods like iterative Boltzmann inversion. We show that our methods can be used to simultaneously fit potentials for simulations at different compositions and temperatures to improve the transferability of the learned potentials.

Fluoroscopy-guided percutaneous lithotripsy using FREDDY laser for giant gallstones: Preliminary experience.

OBJECTIVES: Percutaneous treatment of symptomatic cholelithiasis with large gallstones remains a challenge. We aimed to evaluate the efficacy and safety of a new method for the removal of giant gallstones with percutaneous lithotripsy using a frequency-doubled double-pulse neodymium: YAG (FREDDY) laser. MATERIALS AND METHODS: This study included 16 patients (7 males, 9 females; mean age, 63.4 ± 14.9 years) with giant gallstones who experienced the recurrence of cholecystitis and were not eligible for operation. The percutaneous transcystic approach was established using an 8-French sheath. A 6-French steerable sheath were inserted through the sheath. FREDDY laser lithotripsy was performed to break the stones into fragments. The stone fragments were extracted through the 6-French sheath or pushed into the duodenum using a balloon catheter. Cholecystography was performed before removing the catheter. Follow-up ultrasound or computed tomography examination were performed. RESULTS: Gallstone clearance was accomplished in 16 (100%) patients at the initial assessment. Eleven patients underwent one session, and five patients underwent two sessions. Residual stones were found in 3 (18.8%) patients during the follow-up period. Peritonitis was found in two (12.5%) patients and hemocholecyst was detected in one (6.3%) patient. No procedure-related deaths occurred. CONCLUSION: Percutaneous lithotripsy using a FREDDY laser may be an effective and safe alternative choice for treating giant gallstones, especially for patients who are not eligible for cholecystectomy.

Locally advanced pancreatic carcinoma with jaundice: the benefit of a sequential treatment with stenting followed by CT-guided 125I seeds implantation.

OBJECTIVES: To evaluate the role of sequential therapy with percutaneous biliary stenting and CT-guided iodine-125 seed implantation for locally advanced pancreatic carcinoma with concomitant obstructive jaundice. METHODS: Between January 2016 and December 2018, 42 patients diagnosed with locally advanced pancreatic carcinoma with concomitant obstructive jaundice were enrolled retrospectively. All patients received biliary stenting via percutaneous transhepatic biliary drainage (PTBD) to alleviate obstructive jaundice. Thereafter, twenty-two patients underwent CT-guided iodine-125 seed implantation (treatment group), and 20 did not (control group). The prescribed dose in the treatment group was 110-130 Gy. The clinical data, duration of biliary stent patency, and overall survival (OS) were evaluated. RESULTS: Overall, the total bilirubin level decreased from 275.89 ± 115.44 to 43.08 ± 43.35 µmol/L (p < 0.001) 1 month after percutaneous biliary stenting. In the treatment group, the postoperative median dose covering 90% of the target volume was 129.71 Gy. Compared with the control group, the treatment group had a long mean duration of biliary stent patency and median OS (11.42 vs. 8.57 months, p < 0.01; 11.67 vs. 9.40 months, p < 0.01, respectively). The overall positive response rates 6 months post-treatment in the treatment and control groups were 72.7% (16/22) and 30% (6/20), respectively. Adverse events of more than grade 3 were not observed during the follow-up. CONCLUSION: Sequential therapy with percutaneous biliary stenting and CT-guided iodine-125 seed implantation is an effective and safe treatment alternative for locally advanced pancreatic carcinoma with concomitant obstructive jaundice, which is worthy of clinical application. KEY POINTS: • Obstructive jaundice was alleviated after biliary stent placement in all patients, and the total bilirubin level decreased. • The overall positive response rates at 6 months post-treatment were higher in the treatment group than in the control group, and adverse events of more than grade 3 were not observed during the follow-up period. • Sequential therapy with percutaneous biliary stenting and CT-guided iodine-125 seed implantation can prolong biliary stent patency and improve survival.

Thoracic Endovascular Aortic Repair for Type B Aortic Dissection Associated with Retrograde Type A Intramural Hematoma.

PURPOSE: To evaluate feasibility and efficacy of thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD) associated with retrograde type A intramural hematoma (IMH). MATERIALS AND METHODS: From April 2013 to January 2017, 15 consecutive patients with TBAD associated with retrograde type A IMH who underwent TEVAR were reviewed retrospectively. There was no cardiac tamponade, aortic regurgitation, involvement of coronary artery, or sign of cerebral ischemia in these patients. Enhanced CT was used in 4 patients to diagnose malperfusion of abdominal visceral arteries or lower extremity artery and underwent emergent TEVAR. For the remaining 11 patients, repeated enhanced CT after initial medical treatment within 24 hours from onset of pain showed expansion of IMH in 8 patients or presence of periaortic hematoma in 3 patients. Delayed TEVAR was scheduled for these cases. RESULTS: Successful deployment of the stent graft was achieved in all patients. There were no severe postoperative complications, such as retrograde type A aortic dissection or aortic rupture. Sudden death occurred in 1 patient 3 months after the procedure. Thrombosis of the false lumen, shrinkage of the diameter of the aorta, and complete absorption of the IMH were observed in the remaining patients at a mean follow-up of 19.8 months ± 6.57. CONCLUSIONS: TEVAR for treatment of TBAD with retrograde type A IMH is feasible and effective. It represents a treatment option for patients with TBAD associated with type A IMH with a proximal entry tear located in the descending aorta.

Computed tomography-guided percutaneous microwave ablation with artificial ascites for problematic hepatocellular tumors.

Background: The aim of this study was to assess the feasibility, safety and efficacy of computed tomography (CT)-guided percutaneous microwave ablation with artificial ascites for problematic hepatocellular tumors.Methods: Forty-eight patients with 61 problematic hepatocellular carcinomas who underwent CT-guided percutaneous microwave ablation with artificial ascites were reviewed retrospectively. Lesions less than 5 mm away from the gastrointestinal system, diaphragm, pericardium or kidney were defined as problematic tumors with the potential risk of thermal damage. Microwave ablation was performed after artificial ascites was established between tumors and the adjacent high-risk organs. The technical effectiveness of microwave ablation, local tumor progression and complications was assessed.Results: Microwave ablation with artificial ascites was successfully performed in all 61 tumors. The technical effectiveness rate was 100% with contrast-enhanced CT performed immediately after the ablation procedure. Local tumor progression occurred in three (6%) of the 48 patients during the follow-up period (mean, 15 months; range, 6-24 months). No major complications related to the procedure occurred.Conclusion: CT-guided percutaneous microwave ablation with artificial ascites is a feasible, safe and effective choice for treating problematic hepatocellular tumors, avoiding potential thermal damage to the adjacent high-risk organs.

Temperature-transferable coarse-graining of ionic liquids with dual graph convolutional neural networks.

Computer simulations can provide mechanistic insight into ionic liquids (ILs) and predict the properties of experimentally unrealized ion combinations. However, ILs suffer from a particularly large disparity in the time scales of atomistic and ensemble motion. Coarse-grained models are therefore used in place of costly all-atom simulations, accessing longer time scales and larger systems. Nevertheless, constructing the many-body potential of mean force that defines the structure and dynamics of a coarse-grained system can be complicated and computationally intensive. Machine learning shows great promise for the linked challenges of dimensionality reduction and learning the potential of mean force. To improve the coarse-graining of ILs, we present a neural network model trained on all-atom classical molecular dynamics simulations. The potential of mean force is expressed as two jointly trained neural network interatomic potentials that learn the coupled short-range and many-body long range molecular interactions. These interatomic potentials treat temperature as an explicit input variable to capture its influence on the potential of mean force. The model reproduces structural quantities with high fidelity, outperforms the temperature-independent baseline at capturing dynamics, generalizes to unseen temperatures, and incurs low simulation cost.

Percutaneous stenting and chemotherapy for unresectable pancreatic cancer: Comparison of irradiation stents vs conventional metal stents.

OBJECTIVES: Percutaneous stenting is a palliative method to relieve obstructive jaundice caused by unresectable pancreatic carcinoma. In this study, we aimed to compare the safety and efficacy of irradiation stents and conventional metal stents. METHODS: A total of 32 patients who received irradiation stents or conventional metal stents to treat obstructive jaundice caused by locally advanced pancreatic cancer were included in this retrospective study. Chemotherapy using gemcitabine was performed after jaundice subsided. Stent patency, technical success, survival, and complications were compared between groups. RESULTS: Seventeen patients were enrolled in the irradiation stent group (ISG), and 15 patients were enrolled in the uncovered stent group (USG). Median and mean stent patency time were 9.8 months (95% CI, 7.682-11.981) and 9.506 months (95% CI, 8.0-11.012) in the ISG, respectively, vs 8.8 months (95% CI, 6.528-11.072) and 7.62 months (95% CI, 5.917-9.323) in the USG, respectively (P = 0.019). Median and mean overall survival were 10.4 months (95% CI, 8.383-12.417) and 9.953 months (95% CI, 8.408-11.498), respectively, in the ISG vs 9.7 months (95% CI, 7.901-11.499) and 8.14 months (95% CI, 6.44-9.84), respectively, in the USG (P = 0.027). CONCLUSIONS: Irradiation stents extend stent patency and overall survival compared with conventional biliary stents for the treatment of pancreatic carcinoma complicated by obstructive jaundice. Irradiation stents combined with chemotherapy may be a better choice for the treatment of obstructive jaundice caused by unresectable pancreatic carcinoma.

Percutaneous transcystic balloon dilation for common bile duct stone removal in high-surgical-risk patients with acute cholecystitis and co-existing choledocholithiasis.

BACKGROUND: Percutaneous procedures to treat common bile duct (CBD) stones typically require access via intrahepatic bile ducts. This study aimed to describe the outcomes of a percutaneous transcystic approach that expelled the CBD stones into the duodenum after percutaneous transcystic balloon dilation of the ampulla (PTCBDA) for high-risk patients who present with acute cholecystitis and CBD stones. METHODS: Patients diagnosed with acute cholecystitis and CBD stones who were deemed too high-risk for surgery or general anesthesia and were treated with PTCBDA and CBD stone removal between March 2010 and November 2015 were included for further analysis. Patients underwent emergency percutaneous transhepatic gallbladder drainage under ultrasound. Staged PTCBDA and CBD stone expulsion were performed. Outcomes evaluated included the success rate, causes of failure, and complications. RESULTS: Eighteen patients met the inclusion criteria. CBD stones were successfully expelled in 16 patients. A second procedure was performed in one patient because of residual stones. The procedure failed in two patients because their stones were large. One patient developed bile peritonitis and underwent percutaneous catheter drainage. DISCUSSION: Percutaneous transcystic anterograde expulsion of CBD stones may be a feasible and effective method for treating high-risk surgical patients with acute cholecystitis and co-existing CBD stones.

Study on the mechanism of Shugan Lidan Xiaoshi granule in preventing acute pancreatitis based on network pharmacology and molecular docking.

Background: Shugan Lidan Xiaoshi granules (SLXG) is a herbal granule formulation developed by extensively modifying multiple traditional Chinese medicine compound prescriptions known for their ability to dissolve stones. It is primarily used for the prevention and treatment of cholelithiasis and possesses significant therapeutic potential in both preventing and treating acute pancreatitis. However, the preventive effects of SLXG on cholelithiasis-related complications, such as acute pancreatitis (AP), have been inadequately researched. Methods: TCMSP database was searched to identify the active components and targets of SLXG's action. The disease gene databases (GeneCards, OMMI, PharmGKB, DrugBank) were used to retrieve the targets associated with AP. A TCM ingredient target network was then constructed by using the intersection of these two datasets. The overlapping targets underwent network analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG)and Protein-Protein Interaction (PPI) analyses. Molecular docking was performed to examine the interaction patterns between the active ingredients and central targets. Results: A "Traditional Chinese Medicine-Component-Target" complex network consisting of 10 traditional Chinese medicines, 114 compounds, and 164 targets was constructed. GO and KEGG analysis showed that SLXG has the potential to regulate the response of oxygen-containing compounds, apoptosis, and inflammatory factors. Nine central genes were identified by the PPI network and subnetwork. IL6 was chosen as the most significant gene for molecular docking. The three active compounds of SLXG: quercetin, luteolin, and paeoniflorin, along with the active site of IL6 have a good binding ability and thus play a preventive role in AP. Conclusion: This study provides evidence of the effective preventive role of SLXG against AP, as indicated by bioinformatics analysis. The preventive effect of SLXG is attributed to its multi-component, multi-target, and multi-pathway mechanisms. This finding provides a solid foundation for future research on the clinical application and mechanism of action of drugs.

[Clinical study of percutaneous transhepatic balloon dilation:a novel procedure for common bile duct stone].

OBJECTIVE: To investigate the safety and efficacy of percutaneous transhepatic balloon dilation for the removal of common bile duct stone. METHODS: Sixty-eight cases with common bile duct stone treated with percutaneous transhepatic balloon dilation in our department from July 2008 to April 2011 were analyzed retrospectively.Record CA19-9, total bilirubin, indirect bilirubin and albumin before the procedure, 1 week and 1 month later. Check if immediate complications occurs, including hemorrhage, perforation, pancreatitis and cholangitis. During the following up for 2 years, stone recurrence, reflux cholangitis and other long-term complications were observed. Analyze the changes of indicators between preoperative and postoperative and the correlation. RESULTS: All of the 68 patients were treated successfully.53 patients underwent one procedure, and 15 patients received twice or more times of procedures. CA19-9, TBIL and IBIL decreased significantly 1 week later and 1 month later compared with those before the procedure, while ALB was opposite.Incidences of biliary tract infection, hemorrhage, and pancreatitis were 4.4% (3/68), 2.9% (2/68) and 1.5% (1/68) respectively.No severe complications occurred, including perforation of gastrointestinal or biliary tract.Incidences of recurrent stone and reflux cholangitis were 14.7% (10/68) and 5.9% (4/68) in two years after the procedure. CONCLUSION: Percutaneous transhepatic balloon dilation is a safe and effective procedure for patients with common bile duct stone. For the cases which could not be handled with endoscopic procedures, it provides a new therapeutic approach.

Bronchial artery chemoembolization with drug-eluting beads versus bronchial artery infusion followed by polyvinyl alcohol particles embolization for advanced squamous cell lung cancer: A retrospective study.

PURPOSE: To analyze the efficacy and safety of bronchial arterial embolization (BACE) with drug-eluting beads (DEB) versus bronchial artery infusion (BAI) followed by polyvinyl alcohol (PVA) particle embolization for the treatment of advanced squamous cell lung cancer after the failure of systemic therapy. METHOD: Thirty-six patients with advanced squamous cell lung cancer who underwent bronchial arterial interventional therapy were included in this retrospective study. The DEB group (n = 20) was treated with nedaplatin and DEB loaded with gemcitabine, and the PVA group (n = 16) BAI with nedaplatin and gemcitabine followed by embolization with PVA particles. The treatment efficacy and complications were analyzed. RESULTS: The technical success rate was 100 %. The two groups were followed up for a median period of 8.9 months. The mean overall survival (OS) in the DEB group was 12.6 months (95 % CI:9.99-15.21), which was significantly longer than 8.14 months (95 % CI:6.07-10.2) in the PVA group (p = 0.007). The median progression-free survival (PFS) in the DEB group was 4.3 months (95 % CI:2.33-6.27), significantly longer than 3.2 months (95 % CI:2.55-3.85) in the PVA group (p = 0.030). The objective response rate (ORR) six months after the procedure was 50 % in the DEB group and 12.5 % in the PVA group. In the univariate and multivariate analyses, DEB-BACE was an independent prognostic factor for survival. Only grade 1 adverse events like fever, chest pain, and cough were seen. CONCLUSIONS: DEB-BACE may be a good choice for patients with advanced lung squamous cell carcinoma, as it could prolong OS and PFS without increasing adverse events.

Characterization of circSEC11A as a novel regulator of Iodine-125 radioactive seed-induced anticancer effects in hepatocellular carcinoma via targeting ZHX2/GADD34 axis.

Iodine-125 (I-125) radioactive seed implantation is used for the local treatment of hepatocellular carcinoma (HCC), but the molecular mechanisms regulating its anticancer effects remain incompletely understood. In this study, we report that hsa_circ_0000647 (circSEC11A) is highly expressed after I-125 treatment in HCC cell lines and tissues and is a key regulator of I-125-induced anticancer effects. CircSEC11A acts as a competing endogenous RNA (ceRNA) to sponge miR-3529-3p, promoting the expression of zinc fingers and homeoboxes 2 (ZHX2) and enhancing I-125-induced anticancer effects. Dual-luciferase reporter assay, RNA pull-down, RNA immunoprecipitation, and fluorescence in situ hybridization were thereafter performed to verify the interaction among the molecules. Anticancer effects were detected using CCK-8, flow cytometry, TUNEL, EdU, transwell, and wound healing assays. Furthermore, ZHX2 transcriptionally inhibits GADD34, a negative regulator of endoplasmic reticulum stress (ERS), to enhance I-125- induced anticancer effects in vivo and in vitro. In conclusion, we characterized circSEC11A as a novel regulator of I-125-induced anticancer effects in HCC via miR-3529-3p/ZHX2/GADD34 axis-mediated ERS. Thus, circSEC11A may act as a potential therapeutic target for I-125 implantation in the clinic.

Irradiation stent with 125 I plus TACE versus sorafenib plus TACE for hepatocellular carcinoma with major portal vein tumor thrombosis: a multicenter randomized trial.

BACKGROUND AND AIM: Treatment strategy for hepatocellular carcinoma (HCC) and Vp4 [main trunk] portal vein tumor thrombosis (PVTT) remains limited due to posttreatment liver failure. We aimed to assess the efficacy of irradiation stent placement with 125 I plus transcatheter arterial chemoembolization (TACE) (ISP-TACE) compared to sorafenib plus TACE (Sora-TACE) in these patients. METHODS: In this multicenter randomized controlled trial, participants with HCC and Vp4 PVTT without extrahepatic metastases were enrolled from November 2018 to July 2021 at 16 medical centers. The primary endpoint was overall survival (OS). The secondary endpoints were hepatic function, time to symptomatic progression, patency of portal vein, disease control rate, and treatment safety. RESULTS: Of 105 randomized participants, 51 were assigned to the ISP-TACE group, and 54 were assigned to the Sora-TACE group. The median OS was 9.9 months versus 6.3 months (95% CI: 0.27-0.82; P =0.01). Incidence of acute hepatic decompensation was 16% (8 of 51) versus 33% (18 of 54) ( P =0.036). The time to symptomatic progression was 6.6 months versus 4.2 months (95% CI: 0.38-0.93; P =0.037). The median stent patency was 7.2 months (interquartile range, 4.7-9.3) in the ISP-TACE group. The disease control rate was 86% (44 of 51) versus 67% (36 of 54) ( P =0.018). Incidences of adverse events at least grade 3 were comparable between the safety populations of the two groups: 16 of 49 (33%) versus 18 of 50 (36%) ( P =0.73). CONCLUSION: Irradiation stent placement plus TACE showed superior results compared with sorafenib plus TACE in prolonging OS in patients with HCC and Vp4 PVTT.

Drug-eluting bead transarterial chemoembolization with medium-sized versus small-sized CalliSpheres microspheres in unresectable primary liver cancer.

PURPOSE: The optimal microparticle size for drug-eluting beads transarterial chemoembolization (DEB-TACE) remains unknown. This retrospective cohort study analyzed the efficacy and safety of CalliSpheres microsphere embolization in the treatment of unresectable hepatocellular carcinoma (HCC) to determine the influence of particle size on the results. PATIENTS AND METHODS: Forty-two patients with unresectable HCC were enrolled in this retrospective study from January 2018 to January 2020. Patients received DEB-TACE with CalliSpheres of 100-300 µm (small-size, n = 15) or 300-500 µm (medium-size, n = 27). The tumor response was evaluated via enhanced CT or MRI at 1 month, 3 months, and 6 months after treatment, based on the Modified Response Evaluation Criteria in Solid Tumors. Adverse events after DEB-TACE were recorded. RESULTS: Complete response, partial response, stable disease, and progressive disease were recorded in 20%, 20%, 33.3%, 26.7%, respectively, of patients in the small-size group and 3.7%, 25.9%, 44.4%, 25.9% of patients in the medium-size group, respectively. No significant difference was found between the two groups (p = 0.516). Major adverse events, including grade three liver toxicity (n = 4) and liver abscess (n = 3), occurred significantly more in the small-size group, while none were reported in the medium size group (p < 0.05). CONCLUSION: DEB-TACE with medium-size (300-500 µm) CalliSpheres microspheres had similar efficacy and a better safety profile than DEB-TACE with small-size (100-300 µm) CalliSpheres, indicating that medium-size microspheres may be a better choice for unresectable primary liver cancer.

Endovascular Repair for Acute Type B Aortic Dissection With Unfavorable Proximal Landing Zone.

BACKGROUND: The study aimed to compare the safety and effectiveness between fenestrated technique with or without chimney stent and single-branched stent graft for isolated left subclavian artery revascularization during endovascular repair of acute type B aortic dissection with unfavorable proximal landing zone. METHODS: From January 2016 to December 2019, 65 acute type B aortic dissection patients with unfavorable proximal landing zone were treated with either the fenestrated technique (n = 34, group A) or single-branched stent graft (n = 31, group B). Type I endoleak, retrograde type A dissection, stroke, left subclavian artery patency, 30-day mortality, and aortic remodeling were systematically recorded and retrospectively analyzed. RESULTS: Technical success rates for groups A and group B were 94.12% and 100%, respectively. Left subclavian artery primary patency was achieved for all enrolled patients. The incidence of type I endoleak, retrograde type A dissection, stroke, and 30-day mortality was 5.9%, 5.9%, 2.9%, and 2.9% in group A, respectively, but none were encountered in group B. Left subclavian artery occlusion was observed in 3 patients in group A and 2 patients in group B during a mean follow-up of 16.18 ± 2.08 months and 15.19 ± 2.68 months, respectively. After the procedure, significant aortic remodeling was detected in both groups during follow-up. CONCLUSIONS: Both techniques are feasible and safe for isolated left subclavian artery revascularization during endovascular repair for acute type B aortic dissection. Apart from the associated perioperative risks of complications and mortality for the fenestrated technique, both procedures contributed to favorable aortic remodeling.

The role of bile acid subtypes in the diagnosis of cholangiocarcinoma.

OBJECTIVES: To find the potential biomarkers of cholangiocarcinoma, form a biomarker package, evaluate its efficiency, and validate it. METHODS: R software was used to analyze the differential expression of mRNAs between cholangiocarcinoma and adjacent nontumorous tissues, obtained from The Cancer Genome Atlas (TCGA), and enrich the KEGG pathway. Metabo-Profile Inc. performed the comprehensive bile acid profiling and quantitation. The training set concluded 20 cholangiocarcinoma and 20 nontumorous volunteers. Receiver operating characteristic (ROC) curve and accompanying area under the curve (AUC) was calculated. The top four bile acids formed a new biomarker package. The validation set included 15 cholangiocarcinoma and 15 nontumorous, and the sensitivity and specificity of the new biomarker package were tested. RESULTS: Gene expression of 36 cholangiocarcinoma and nine adjacent nontumorous tissues was obtained in January 2020. Totally 9887 differential genes were eligible (logFC ≥ 1 or ≤ -1, P < 0.05, and adjust P < 0.01). GO analysis showed that 20 KEGG pathways were enriched, including primary bile acid biosynthesis and bile secretion. Comprehensive bile acid profiling and quantitation showed 15 differential bile acid types, and the ROC-AUC was between 0.953 and 0.750. HDCA, isoLCA, bCDCA, and DCA were selected to form a biomarker package. The Logit (p = cholangiocarcinoma) = 7.898 - 3.70*(1isoLCA) - 0.444*(bCDCA) + 0.415*(HDCA) + 0.041*DCA. Its ROC-AUC was 0.944. In the validation set, the sensitivity was 0.933 and the specificity was 0.867. CONCLUSION: Bile acid types package was efficient to distinguish nontumorous population and cholangiocarcinoma. The difference might be associated to the downregulation of primary bile acid biosynthesis and bile secretion pathway of cholangiocarcinoma.

CT-guided iodine-125 brachytherapy as salvage therapy for recurrent mediastinal lymph node metastasis.

BACKGROUND: The treatment of recurrent mediastinal lymph node metastasis (MLNMs) is challenging. We conducted this study to evaluate the effectiveness and safety of computed tomography (CT)-guided percutaneous iodine-125 brachytherapy for MLNMs. METHODS: We retrospectively analyzed 33 patients with recurrent MLNMs treated with CT-guided interstitial implantation of iodine-125 seeds. Regular contrast-enhanced CT was conducted to evaluate the tumor response. Follow-up survival, quality of life, and adverse events were analyzed. RESULTS: The number of implanted seeds was 16-85 (median, 40). The matched peripheral dose was 110-160 Gy. The patients were followed up for 5-24 months (median, 14 months). At the last follow-up or death, complete response to therapy was achieved in 11 patients (33.3%) and partial response in 18 patients (54.5%). The median survival time of this cohort was 15.2 months (95% confidence interval [CI], 9.9-20.5 months); the estimated one- and two-year survival rates were 68.6% and 31.1%, respectively. The Karnofsky performance score increased significantly after the procedure (p = 0.007). Pneumothorax with pulmonary compression of 30% to 40% occurred in five (15.2%) patients and was cured after drainage. No severe complications occurred. CONCLUSIONS: CT-guided iodine-125 brachytherapy provided a safe and effective choice for recurrent mediastinal lymph node metastasis with significant local therapeutic effects and minor complications, especially for patients who were not eligible for surgical resection and had failed to benefit from systemic therapy.