Successful Percutaneous Ultrasonic Lithotripsy of Gallstones.

Background: Acute calculous cholecystitis is the obstruction of the cystic duct by a gallstone that leads to inflammation of the gallbladder necessitating cholecystectomy. Case Series: We present the cases of 2 patients with acute calculous cholecystitis who were deemed ineligible candidates for cholecystectomy because of their complicating medical histories. Both patients initially underwent cholecystostomy and drain placement with interventional radiology for management of acute calculous cholecystitis. Their large gallstones remained refractory to attempts at removal by electrohydraulic lithotripsy via the cholecystostomy access. The patients' gallstones were successfully removed via percutaneous ultrasonic lithotripsy during a collaborative procedure with interventional radiology and urology. Conclusion: An interdisciplinary approach using percutaneous cholecystolithotomy with rigid ultrasonic lithotripsy is an effective method for removing challenging gallstones in patients for whom traditional approaches fail.

Impact of General Anesthesia on the Right Atrial Pressure During Transjugular Intrahepatic Portosystemic Shunt Creation: A Propensity Score Match Analysis.

PURPOSE: To evaluate the effect of general anesthesia on right atrial (RA) pressure measurements during transjugular intrahepatic portosystemic shunt (TIPS) placement using propensity score match analysis. MATERIALS: A single-institution database was used to identify 664 patients who underwent TIPS creation under either conscious sedation (CS) or general anesthesia (GA) between 2009 and 2018. A propensity-matched cohort was created using logistic regression of sedation method on demographics, liver disease status, and indications. Paired analyses were performed using mixed models for RA pressure and Cox proportional hazards model with robust standard errors for mortality. RESULTS: Of the 664 patients, 270 patients were matched based on similar characteristics (135 for GA and 135 for CS). Indications for TIPS creation included intractable ascites (n = 170, 63%), hepatic hydrothorax (n = 30, 11%), variceal bleeding (n = 43, 16%), and other (n = 27, 10%). Pre-TIPS RA pressure was greater in the matched GA group as compared to CS group by a mean of 4.2 mmHg (p < 0.0001). Similarly, post-TIPS RA pressure was greater in the matched GA group as compared to CS group by a mean of 3.3 mmHg (p < 0.0001). Pre- and post-procedure RA pressure was found to have no association with post-procedure mortality (0.8891, HR 1.077; p 0.917, HR 0.997; respectively). CONCLUSIONS: Utilization of GA during TIPS creation raises the intra-procedural RA pressure compared to CS. However, this elevated intra-procedural RA pressure does not appear to be predictive of mortality post-TIPS creation.

High-Force Application by a Nanoscale DNA Force Spectrometer.

The ability to apply and measure high forces (>10 pN) on the nanometer scale is critical to the development of nanomedicine, molecular robotics, and the understanding of biological processes such as chromatin condensation, membrane deformation, and viral packaging. Established force spectroscopy techniques including optical traps, magnetic tweezers, and atomic force microscopy rely on micron-sized or larger handles to apply forces, limiting their applications within constrained geometries including cellular environments and nanofluidic devices. A promising alternative to these approaches is DNA-based molecular calipers. However, this approach is currently limited to forces on the scale of a few piconewtons. To study the force application capabilities of DNA devices, we implemented DNA origami nanocalipers with tunable mechanical properties in a geometry that allows application of force to rupture a DNA duplex. We integrated static and dynamic single-molecule characterization methods and statistical mechanical modeling to quantify the device properties including force output and dynamic range. We found that the thermally driven dynamics of the device are capable of applying forces of at least 20 piconewtons with a nanometer-scale dynamic range. These characteristics could eventually be used to study other biomolecular processes such as protein unfolding or to control high-affinity interactions in nanomechanical devices or molecular robots.

North American Practice-Based Recommendations for Transjugular Intrahepatic Portosystemic Shunts in Portal Hypertension.

Complications of portal hypertension, including ascites, gastrointestinal bleeding, hepatic hydrothorax, and hepatic encephalopathy, are associated with significant morbidity and mortality. Despite few high-quality randomized controlled trials to guide therapeutic decisions, transjugular intrahepatic portosystemic shunt (TIPS) creation has emerged as a crucial therapeutic option to treat complications of portal hypertension. In North America, the decision to perform TIPS involves gastroenterologists, hepatologists, and interventional radiologists, but TIPS creation is performed by interventional radiologists. This is in contrast to other parts of the world where TIPS creation is performed primarily by hepatologists. Thus, the successful use of TIPS in North America is dependent on a multidisciplinary approach and technical expertise, so as to optimize outcomes. Recently, new procedural techniques, TIPS stent technology, and indications for TIPS have emerged. As a result, practices and outcomes vary greatly across institutions and significant knowledge gaps exist. In this consensus statement, the Advancing Liver Therapeutic Approaches group critically reviews the application of TIPS in the management of portal hypertension. Advancing Liver Therapeutic Approaches convened a multidisciplinary group of North American experts from hepatology, interventional radiology, transplant surgery, nephrology, cardiology, pulmonology, and hematology to critically review existing literature and develop practice-based recommendations for the use of TIPS in patients with any cause of portal hypertension in terms of candidate selection, procedural best practices and, post-TIPS management; and to develop areas of consensus for TIPS indications and the prevention of complications. Finally, future research directions are identified related to TIPS for the management of portal hypertension.

A nanoscale DNA force spectrometer capable of applying tension and compression on biomolecules.

Single molecule force spectroscopy is a powerful approach to probe the structure, conformational changes, and kinetic properties of biological and synthetic macromolecules. However, common approaches to apply forces to biomolecules require expensive and cumbersome equipment and relatively large probes such as beads or cantilevers, which limits their use for many environments and makes integrating with other methods challenging. Furthermore, existing methods have key limitations such as an inability to apply compressive forces on single molecules. We report a nanoscale DNA force spectrometer (nDFS), which is based on a DNA origami hinge with tunable mechanical and dynamic properties. The angular free energy landscape of the nDFS can be engineered across a wide range through substitution of less than 5% of the strand components. We further incorporate a removable strut that enables reversible toggling of the nDFS between open and closed states to allow for actuated application of tensile and compressive forces. We demonstrate the ability to apply compressive forces by inducing a large bend in a 249bp DNA molecule, and tensile forces by inducing DNA unwrapping of a nucleosome sample. These results establish a versatile tool for force spectroscopy and robust methods for designing nanoscale mechanical devices with tunable force application.

Final Two-Year Outcomes for the Sentry Bioconvertible Inferior Vena Cava Filter in Patients Requiring Temporary Protection from Pulmonary Embolism.

PURPOSE: To report final 2-year outcomes with the Sentry bioconvertible inferior vena cava (IVC) filter in patients requiring temporary protection against pulmonary embolism (PE). MATERIALS AND METHODS: In a prospective multicenter trial, the Sentry filter was implanted in 129 patients with documented deep vein thrombosis (DVT) and/or PE (67.5%) or who were at temporary risk of developing DVT/PE (32.6%). Patients were monitored and bioconversion status ascertained by radiography, computed tomography (CT), and CT venography through 2 years. RESULTS: The composite primary 6-month endpoint of clinical success was achieved in 97.4% (111/114) of patients. The rate of new symptomatic PE was 0% (n = 126) through 1 year and 2.4% (n = 85) through the second year of follow-up, with 2 new nonfatal cases at 581 and 624 days that were adjudicated as not related to the procedure or device. Two patients (1.6%) developed symptomatic caval thrombosis during the first month and underwent successful interventions without recurrence. No other filter-related symptomatic complications occurred through 2 years. There was no filter tilting, migration, embolization, fracture, or caval perforation and no filter-related deaths through 2 years. Filter bioconversion was successful for 95.7% (110/115) of patients at 6 months, 96.4% (106/110) of patients at 12 months, and 96.5% (82/85) of patients at 24 months. Through 24 months of follow-up, there was no evidence of late-stage IVC obstruction or thrombosis after filter bioconversion or of thrombogenicity associated with retracted filter arms. CONCLUSIONS: The Sentry IVC filter provided safe and effective protection against PE, with a high rate of intended bioconversion and a low rate of device-related complications, through 2 years of follow-up.

Quantitative Modeling of Nucleosome Unwrapping from Both Ends.

In eukaryotic cells, DNA is packaged into chromatin where nucleosomes are the basic packaging unit. Important cellular processes including gene expression, DNA replication, and DNA repair require nucleosomal DNA to be unwrapped so that functional proteins can access their target sites, which otherwise are sterically occluded. A key question in this process is what the unwrapped conformations individual nucleosomes adopt within chromatin are. Here, we develop a concurrent nucleosome unwrapping model to address this question. We hypothesize that for a given end-to-end distance of the nucleosomal DNA, the nucleosomal DNA stochastically unwraps from the histone core from both ends independently and that this combination of unwrapping from both sides results in a significant increase in the average distance between the DNA extending from both sides of the nucleosomes. We test our model on recently published experiments using a DNA origami nanocaliper that quantifies nucleosome unwrapping and achieve good agreement between experiment and model prediction. We then investigate the DNA origami caliper distribution when attached to a hexasome (a nucleosome lacking an H2A/H2B dimer). A significant shift in the caliper angle distribution caused by the asymmetric structural features of the hexasome seen experimentally is consistent with the model. Our modeling approach may be more broadly useful to the interpretation of other studies of nucleosome dynamics, chromatin dynamics, and regulatory processes involving nucleosome unwrapping, as well as more generally to optimization of future DNA origami designs to probe mechanical properties of biomolecules.

Percutaneous Cholecystolithotomy Using Cholecystoscopy.

The morbidity and mortality of cholecystectomy can increase to 10% in high surgical risk patients. The technique for percutaneous cholecystolithotomy consists of 3 steps: (1) percutaneous cholecystostomy, (2) tract dilation and cholecystolithotomy, and (3) tract evaluation and catheter removal. Cholecystoscopy is critical in guiding the lithotripsy probe for fragmentation of large stones and is useful for locating small stone fragments not seen in cholangiography. Cholecystoscopy is also useful for assessing ambiguous lesions and in distinguishing between stone vs debris or mass. Technical success rate of percutaneous cholecystolithotomy using cholecystoscopy ranges from 93% to 100%. Procedure related complication rate has been reported as 4%-15%. The most common complication is bile leak during the procedure or after catheter removal. Although recurrence rate of gallstones has been reported up to 40%, the symptom recurrence rate is much lower. Therefore, percutaneous cholecystolithotomy using cholecystoscopy can be an alternative to cholecystectomy in high surgical risk patients with symptomatic gallstones.

Propensity-matched comparison of transjugular intrahepatic portosystemic shunt placement techniques: Intracardiac echocardiography (ICE) versus fluoroscopic guidance.

PURPOSE: To compare procedure characteristics and outcomes when TIPS is performed under intracardiac echocardiography guidance (iTIPS) compared to conventional fluoroscopic guidance (cTIPS). MATERIALS AND METHODS: A retrospective propensity-matched study of 30 iTIPS and 30 cTIPS procedures from January 2014 to March 2017 at a single US high volume academic medical center was performed. iTIPS and cTIPS cases were propensity score matched using predictive variables: age, race, gender, etiology of liver disease, indication for TIPS, MELD score, and portal vein patency. Procedure characteristics and post- procedure outcomes were compared between propensity-matched groups including: total procedure time, technical success, radiation dose, contrast volume, complication rate, 30- day mortality, and revision rate within 3 months. RESULTS: Radiation dose (875.3 vs 457.4 mGY, p = 0.039) and contrast volume (141 vs 103 mL, p = 0.005) were significantly decreased in the iTIPS versus the cTIPS group. There was no significant difference in procedure time (81.5 cTIPS vs 84 min iTIPS) or rate of TIPS revisions within 3 months. Average operator experience in the iTIPs group was 4.2 years and cTIPS group 11.0 years (p = 0.0004). All procedures were technically successful with no mortalities within 30 days. CONCLUSION: iTIPS resulted in significantly reduced radiation dose and contrast volume. However, there was no difference in total procedure time or overall outcomes despite greater operator experience in the cTIPS group.

Cryoablation of low-flow vascular malformations.

PURPOSE: We aimed to evaluate the safety and effectiveness of cryoablation in the treatment of low-flow malformations, specifically venous malformation (VM) and fibroadipose vascular anomaly (FAVA). METHODS: We conducted a retrospective review of 11 consecutive patients with low-flow malformations (14 lesions; 9 VM, 5 FAVA), median lesion volume 10.8 cm3, (range, 1.8-55.6 cm3) with a median age of 19 years (range, 10-50 years) who underwent cryoablation to achieve symptomatic control. Average follow-up was at a median of 207 days postprocedure (range, 120-886 days). Indications for treatment included focal pain and swelling. Technical success was achieved if the cryoablation ice ball covered the region of the malformation that corresponded to the patient's symptoms. Clinical success was considered complete if all symptoms resolved and partial if some symptoms persisted but did not necessitate further treatment. RESULTS: The technical success rate was 100%. At 1-month follow-up, 13 of 14 lesions (93%) had a complete response and one (7%) had a partial response. At 6-month follow-up 12 of 13 (92%) had a complete response and 1 (8%) had a partial response. A total of 6 patients underwent primary cryoablation. Out of 9 VM cases, 7 had prior sclerotherapy and 2 had primary cryoablation. Out of the 5 FAVA cases, 1 had prior sclerotherapy and the remaining 4 cases underwent primary cryoablation. There were 3 minor complications following cryoablation including 2 cases of skin blisters and 1 case of transient numbness. These complications resolved with conservative management. CONCLUSION: Cryoablation is safe and effective in the treatment of low-flow vascular malformations, either after sclerotherapy or as primary treatment.

One-Year Analysis of the Prospective Multicenter SENTRY Clinical Trial: Safety and Effectiveness of the Novate Sentry Bioconvertible Inferior Vena Cava Filter.

PURPOSE: To prospectively assess the Sentry bioconvertible inferior vena cava (IVC) filter in patients requiring temporary protection against pulmonary embolism (PE). MATERIALS AND METHODS: At 23 sites, 129 patients with documented deep vein thrombosis (DVT) or PE, or at temporary risk of developing DVT or PE, unable to use anticoagulation were enrolled. The primary end point was clinical success, including successful filter deployment, freedom from new symptomatic PE through 60 days before filter bioconversion, and 6-month freedom from filter-related complications. Patients were monitored by means of radiography, computerized tomography (CT), and CT venography to assess filtering configuration through 60 days, filter bioconversion, and incidence of PE and filter-related complications through 12 months. RESULTS: Clinical success was achieved in 111 of 114 evaluable patients (97.4%, 95% confidence interval [CI] 92.5%-99.1%). The rate of freedom from new symptomatic PE through 60 days was 100% (n = 129, 95% CI 97.1%-100.0%), and there were no cases of PE through 12 months for either therapeutic or prophylactic indications. Two patients (1.6%) developed symptomatic caval thrombosis during the first month; neither experienced recurrence after successful interventions. There was no filter tilting, migration, embolization, fracture, or caval perforation by the filter, and no filter-related death through 12 months. Filter bioconversion was successful for 95.7% (110/115) at 6 months and for 96.4% (106/110) at 12 months. CONCLUSIONS: The Sentry IVC filter provided safe and effective protection against PE, with a high rate of intended bioconversion and a low rate of device-related complications, through 12 months of imaging-intense follow-up.

Liver-dominant Breast Cancer Metastasis: A Comparative Outcomes Study of Chemoembolization Versus Radioembolization.

AIM: To compare toxicity, response, and survival outcomes of patients with hepatic metastases from breast cancer who underwent transarterial chemoembolization (TACE) or radioembolization (TARE). MATERIALS AND METHODS: A retrospective review was carried out of all patients who underwent TACE or TARE for liver-dominant breast cancer metastases between January 2006 and March 2016 at an academic medical center in the United States. RESULTS: Seventeen patients in the TACE group and 30 patients in the TARE group received 32 TACE and 49 TARE treatments, respectively. Median follow-up was 9 months. Both groups had similar background variables. More all-grade adverse events were seen in the TACE group (71% vs. 44%; p=0.02). Median overall survival in the TACE group was 4.6 months compared to 12.9 months in the TARE group (p=0.2349). Treatment type was not an independent prognostic factor. CONCLUSION: TARE is better tolerated than TACE for the treatment of liver-dominant breast cancer metastasis. There was a trend towards improved survival with TARE; however, it did not approach statistical significance. Larger studies are needed to validate these findings.

Modified Balloon-Occluded Retrograde Transvenous Obliteration (BRTO) Techniques for the Treatment of Gastric Varices: Vascular Plug-Assisted Retrograde Transvenous Obliteration (PARTO)/Coil-Assisted Retrograde Transvenous Obliteration (CARTO)/Balloon-Occluded Antegrade Transvenous Obliteration (BATO).

Gastric varices in the setting of portal hypertension occur less frequently than esophageal varices but occur at lower portal pressures and are associated with more massive bleeding events and higher mortality rate. Balloon-occluded retrograde transvenous obliteration (BRTO) of gastric varices has been well documented as an effective therapy for portal hypertensive gastric varices. However, BRTO requires lengthy, higher-level post-procedural monitoring and can have complications related to balloon rupture and adverse effects of sclerosing agents. Several modified BRTO techniques have been developed including vascular plug-assisted retrograde transvenous obliteration, coil-assisted retrograde transvenous obliteration, and balloon-occluded antegrade transvenous obliteration. This article provides an overview of various modified BRTO techniques.

Covalent Modifications of Histone H3K9 Promote Binding of CHD3.

Chromatin remodeling is required for genome function and is facilitated by ATP-dependent complexes, such as nucleosome remodeling and deacetylase (NuRD). Among its core components is the chromodomain helicase DNA binding protein 3 (CHD3) whose functional significance is not well established. Here, we show that CHD3 co-localizes with the other NuRD subunits, including HDAC1, near the H3K9ac-enriched promoters of the NuRD target genes. The tandem PHD fingers of CHD3 bind histone H3 tails and posttranslational modifications that increase hydrophobicity of H3K9-methylation or acetylation (H3K9me3 or H3K9ac)-enhance this interaction. Binding of CHD3 PHDs promotes H3K9Cme3-nucleosome unwrapping in vitro and perturbs the pericentric heterochromatin structure in vivo. Methylation or acetylation of H3K9 uniquely alleviates the intra-nucleosomal interaction of histone H3 tails, increasing H3K9 accessibility. Collectively, our data suggest that the targeting of covalently modified H3K9 by CHD3 might be essential in diverse functions of NuRD.

Long-term outcome of upper extremity arteriovenous fistula using pSLOT: single-center longitudinal follow-up using a protocol-based approach.

INTRODUCTION: Functional arteriovenous fistula (AVF) is the best vascular access for end-stage renal disease patients. AVF maturation is variable and many require additional interventions to achieve functionality. Long-term benefits of such interventions are unclear. Using a protocol for AVF planning, creation, maturation evaluation and performing interventions based on objective findings along with maintaining a database on follow-up is necessary to evaluate this question.The aim of this study is to evaluate the long-term outcome of newly constructed AVFs using a protocol-based approach in a tertiary care academic center. METHODS: This is an observational study. Long-term outcomes of consecutive AVFs placed over a 5-year period using a protocol for creation, maturation evaluation and interventions based on objective findings were analyzed using a prospectively maintained clinical database. RESULTS: Functioning AVFs were achieved in 86.5% (n = 296) of 342 patients. Primary and secondary patency of 372 AVF procedures at 12, 24 and 60 months were 42.8%, 31.6% and 20.8%; and 81.8%, 77.6% and 71.7%, respectively. Functional patency at 12, 24 and 60 months were 95.1%, 88.7%, and 85.2%, respectively. Long-term function was similar for AVFs maturing with ≤4 interventions and without interventions. AVFs maturing with 2-4 interventions needed significantly more interventions to maintain long-term functional patency (p = 0.003). CONCLUSIONS: Piggyback straight-line on-lay technique (pSLOT) improves early outcome providing opportunity to identify other problems contributing to non-maturation. A large number of AVFs needing planned interventions to mature provide good long-term function. Establishing process of care guidelines for creation and follow-up has a potential to improve AVF outcome.

Hemobilia Due to Cystic Artery Pseudoaneurysm: A Rare Late Complication of Laparoscopic Cholecystectomy.

We discuss a patient with late presentation of hemobilia following cholecystectomy, which is unusual because pseudoaneurysm caused by vascular injury during surgery typically presents soon after surgery. Endoscopic retrograde cholangiopancreatography revealed a large blood clot arising from the biliary orifice with subsequent computed tomography angiography diagnosing a large pseudoaneurysm in the region of the cystic artery adjacent to the cholecystectomy clips. Embolization was performed via direct percutaneous puncture of the pseudoaneurysm.

Laparoscopic Nephrectomy: Initial Case Report.

A tumor-bearing right kidney was completely excised from an 85-year-old woman using a laparoscopic approach. A newly devised method for intra-abdominal organ entrapment and a recently developed laparoscopic tissue morcellator made it possible to deliver the 190 gm. kidney through an 11 mm. incision.