Progranulin Deficiency Promotes Circuit-Specific Synaptic Pruning by Microglia via Complement Activation.

Microglia maintain homeostasis in the brain, but whether aberrant microglial activation can cause neurodegeneration remains controversial. Here, we use transcriptome profiling to demonstrate that deficiency in frontotemporal dementia (FTD) gene progranulin (Grn) leads to an age-dependent, progressive upregulation of lysosomal and innate immunity genes, increased complement production, and enhanced synaptic pruning in microglia. During aging, Grn(-/-) mice show profound microglia infiltration and preferential elimination of inhibitory synapses in the ventral thalamus, which lead to hyperexcitability in the thalamocortical circuits and obsessive-compulsive disorder (OCD)-like grooming behaviors. Remarkably, deleting C1qa gene significantly reduces synaptic pruning by Grn(-/-) microglia and mitigates neurodegeneration, behavioral phenotypes, and premature mortality in Grn(-/-) mice. Together, our results uncover a previously unrecognized role of progranulin in suppressing aberrant microglia activation during aging. These results represent an important conceptual advance that complement activation and microglia-mediated synaptic pruning are major drivers, rather than consequences, of neurodegeneration caused by progranulin deficiency.

Advances in the treatment of intrahepatic cholangiocarcinoma: An overview of the current and future therapeutic landscape for clinicians.

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver tumor and remains a fatal malignancy in the majority of patients. Approximately 20%-30% of patients are eligible for resection, which is considered the only potentially curative treatment; and, after resection, a median survival of 53 months has been reported when sequenced with adjuvant capecitabine. For the 70%-80% of patients who present with locally unresectable or distant metastatic disease, systemic therapy may delay progression, but survival remains limited to approximately 1 year. For the past decade, doublet chemotherapy with gemcitabine and cisplatin has been considered the most effective first-line regimen, but results from the recent use of triplet regimens and even immunotherapy may shift the paradigm. More effective treatment strategies, including those that combine systemic therapy with locoregional therapies like radioembolization or hepatic artery infusion, have also been developed. Molecular therapies, including those that target fibroblast growth factor receptor and isocitrate dehydrogenase, have recently received US Food and Drug Administration approval for a defined role as second-line treatment for up to 40% of patients harboring these actionable genomic alterations, and whether they should be considered in the first-line setting is under investigation. Furthermore, as the oncology field seeks to expand indications for immunotherapy, recent data demonstrated that combining durvalumab with standard cytotoxic therapy improved survival in patients with ICC. This review focuses on the current and future strategies for ICC treatment, including a summary of the primary literature for each treatment modality and an algorithm that can be used to drive a personalized and multidisciplinary approach for patients with this challenging malignancy.

Neutrophils prime a long-lived effector macrophage phenotype that mediates accelerated helminth expulsion.

We examined the role of innate cells in acquired resistance to the natural murine parasitic nematode, Nippostrongylus brasiliensis. Macrophages obtained from lungs as late as 45 d after N. brasiliensis inoculation were able to transfer accelerated parasite clearance to naive recipients. Primed macrophages adhered to larvae in vitro and triggered increased mortality of parasites. Neutrophil depletion in primed mice abrogated the protective effects of transferred macrophages and inhibited their in vitro binding to larvae. Neutrophils in parasite-infected mice showed a distinct transcriptional profile and promoted alternatively activated M2 macrophage polarization through secretory factors including IL-13. Differentially activated neutrophils in the context of a type 2 immune response therefore prime a long-lived effector macrophage phenotype that directly mediates rapid nematode damage and clearance.

An End-to-End Platform for Digital Pathology Using Hyperspectral Autofluorescence Microscopy and Deep Learning-Based Virtual Histology.

Conventional histopathology involves expensive and labor-intensive processes that often consume tissue samples, rendering them unavailable for other analyses. We present a novel end-to-end workflow for pathology powered by hyperspectral microscopy and deep learning. First, we developed a custom hyperspectral microscope to nondestructively image the autofluorescence of unstained tissue sections. We then trained a deep learning model to use autofluorescence to generate virtual histologic stains, which avoids the cost and variability of chemical staining procedures and conserves tissue samples. We showed that the virtual images reproduce the histologic features present in the real-stained images using a randomized nonalcoholic steatohepatitis (NASH) scoring comparison study, where both real and virtual stains are scored by pathologists (D.T., A.D.B., R.K.P.). The test showed moderate-to-good concordance between pathologists' scoring on corresponding real and virtual stains. Finally, we developed deep learning-based models for automated NASH Clinical Research Network score prediction. We showed that the end-to-end automated pathology platform is comparable with an independent panel of pathologists for NASH Clinical Research Network scoring when evaluated against the expert pathologist consensus scores. This study provides proof of concept for this virtual staining strategy, which could improve cost, efficiency, and reliability in pathology and enable novel approaches to spatial biology research.

Molecular definition of the identity and activation of natural killer cells.

Using whole-genome microarray data sets of the Immunological Genome Project, we demonstrate a closer transcriptional relationship between NK cells and T cells than between any other leukocytes, distinguished by their shared expression of genes encoding molecules with similar signaling functions. Whereas resting NK cells are known to share expression of a few genes with cytotoxic CD8(+) T cells, our transcriptome-wide analysis demonstrates that the commonalities extend to hundreds of genes, many encoding molecules with unknown functions. Resting NK cells demonstrate a 'preprimed' state compared with naive T cells, which allows NK cells to respond more rapidly to viral infection. Collectively, our data provide a global context for known and previously unknown molecular aspects of NK cell identity and function by delineating the genome-wide repertoire of gene expression of NK cells in various states.

Embolization of the Pancreas Using Microspheres: A Proof-of-Safety Study in a Porcine Model.

INTRODUCTION: Particle embolization of the pancreas with the intent of producing tissue ischemia has not been evaluated, but could have valuable application in the oncologic realm. A pig model was used to evaluate safety and impact on pancreatic function. METHODS: Embolization of the dorsal pancreatic artery using 100-300-micron particles was performed on fourteen Yorkshire pigs. Baseline and post-embolization glucose tolerance testing and serum amylase/lipase levels were obtained. Pigs were observed for two weeks to assess for behavioral signs of pain/distress, bowel changes, and changes to intake/output. After two weeks, euthanasia and necropsy with gross and histopathologic assessment of the pancreas was performed. RESULTS: Embolization was technically successful in all pigs. All animals survived the two-week follow up without evidence of pain/distress. There were significant increases in amylase and lipase at 24- and 48-hours (p < 0.001), which normalized by two weeks. There clinically significant change in glucose tolerance testing at 2 weeks. Bowel habits were unchanged without diarrhea. At necropsy, all examined pancreases had fibrosis in the distal body and tail, without gross evidence of ongoing inflammation. On histopathologic evaluation, all pancreases demonstrated fibrosis in the embolized portions without evidence of active inflammation in treated or adjacent pancreatic tissue. CONCLUSION: Particle embolization of the pancreas was feasible and tolerated by all tested pigs with transient amylasemia, lipasemia, and mildly impaired glucose tolerance, but without clinical or histopathologic evidence of acute pancreatitis and no evident impact on pancreatic endocrine or exocrine function.

Correlation of ablation volume with renal function loss after cryoablation in solitary functioning kidneys.

PURPOSE: The purpose of this study was to retrospectively analyze the degree of renal function deterioration after renal cryoablation in patients with a solitary functioning kidney based on ablation volume. MATERIALS AND METHODS: Over a 15-year period, 81 percutaneous cryoablations were performed in solitary functioning kidneys. After exclusion of patients with baseline end-stage renal disease(ESRD) and insufficient follow up, analysis was performed on 65 procedures in 52 patients (40 male, mean age 63.5 years). The post-cryoablation renal function was based on the lowest serum creatinine within 6 months post-procedure. Renal function change was defined as percentage glomerular filtration rate(GFR) change. Volumetric analysis was performed on the target lesion, renal parenchyma, and ablation zone. RESULTS: The median tumor diameter was 2.0cm (range 0.8-4.7cm). The median baseline GFR decreased from 56.4 mL/min/1.73m2 (range 17.5-89.7) to 46.9 (range 16.5-89.7) at median 95 days (p<0.001), equating to an -7.9% median renal function change (range -45.0 to +30.7). All patients had stage 2 or worse chronic kidney disease and baseline function did not correlate with renal function change. The median volume of ablated parenchyma was 19.7mL (range 2.4-87.3mL), equating to 8.1% (range 0.7-37.2%) of total parenchyma. The volume of parenchymal volume ablated correlated significantly with renal function loss, while age, hypertension, and diabetes mellitus did not. No patients developed ESRD within 1 year after cryoablation. CONCLUSION: Cryoablation in solitary functioning kidneys resulted in a modest reduction in renal function, even in patients with chronic kidney disease and ablations up to 20% of renal parenchymal volume.

Multi-omic profiling reveals early immunological indicators for identifying COVID-19 Progressors.

We sought to better understand the immune response during the immediate post-diagnosis phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by identifying molecular associations with longitudinal disease outcomes. Multi-omic analyses identified differences in immune cell composition, cytokine levels, and cell subset-specific transcriptomic and epigenomic signatures between individuals on a more serious disease trajectory (Progressors) as compared to those on a milder course (Non-progressors). Higher levels of multiple cytokines were observed in Progressors, with IL-6 showing the largest difference. Blood monocyte cell subsets were also skewed, showing a comparative decrease in non-classical CD14-CD16+ and intermediate CD14+CD16+ monocytes. In lymphocytes, the CD8+ T effector memory cells displayed a gene expression signature consistent with stronger T cell activation in Progressors. These early stage observations could serve as the basis for the development of prognostic biomarkers of disease risk and interventional strategies to improve the management of severe COVID-19. BACKGROUND: Much of the literature on immune response post-SARS-CoV-2 infection has been in the acute and post-acute phases of infection. TRANSLATIONAL SIGNIFICANCE: We found differences at early time points of infection in approximately 160 participants. We compared multi-omic signatures in immune cells between individuals progressing to needing more significant medical intervention and non-progressors. We observed widespread evidence of a state of increased inflammation associated with progression, supported by a range of epigenomic, transcriptomic, and proteomic signatures. The signatures we identified support other findings at later time points and serve as the basis for prognostic biomarker development or to inform interventional strategies.

Comparing Survival After Resection, Ablation, and Radiation in Small Intrahepatic Cholangiocarcinoma.

BACKGROUND: Hepatectomy is the cornerstone of curative-intent treatment for intrahepatic cholangiocarcinoma (ICC). However, in patients unable to be resected, data comparing efficacy of alternatives including thermal ablation and radiation therapy (RT) remain limited. Herein, we compared survival between resection and other liver-directed therapies for small ICC within a national cancer registry. PATIENTS AND METHODS: Patients with clinical stage I-III ICC < 3 cm diagnosed 2010-2018 who underwent resection, ablation, or RT were identified in the National Cancer Database. Overall survival (OS) was compared using Kaplan-Meier and multivariable Cox proportional hazards methods. RESULTS: Of 545 patients, 297 (54.5%) underwent resection, 114 (20.9%) ablation, and 134 (24.6%) RT. Median OS was similar between resection and ablation [50.5 months, 95% confidence interval (CI) 37.5-73.9; 39.5 months, 95% CI 28.7-58.4, p = 0.14], both exceeding that of RT (20.9 months, 95% CI 14.1-28.3). RT patients had high rates of stage III disease (10.4% RT vs. 1.8% ablation vs. 11.8% resection, p < 0.001), but the lowest rates of chemotherapy utilization (9.0% RT vs. 15.8% ablation vs. 38.7% resection, p < 0.001). In multivariable analysis, resection and ablation were associated with reduced mortality compared with RT [hazard ratio (HR) 0.44, 95% CI 0.33-0.58 and HR 0.53, 95% CI 0.38-0.75, p < 0.001, respectively]. CONCLUSION: Resection and ablation were associated with improved survival in patients with ICC < 3 cm compared with RT. Acknowledging confounders, anatomic constraints of ablation, limitations of available data, and need for prospective study, these results favor ablation in small ICC where resection is not feasible.

Updates on LI-RADS Treatment Response Criteria for Hepatocellular Carcinoma: Focusing on MRI.

As the incidence of hepatocellular carcinoma (HCC) and subsequent treatments with liver-directed therapies rise, the complexity of assessing lesion response has also increased. The Liver Imaging Reporting and Data Systems (LI-RADS) treatment response algorithm (LI-RADS TRA) was created to standardize the assessment of response after locoregional therapy (LRT) on contrast-enhanced CT or MRI. Originally created based on expert opinion, these guidelines are currently undergoing revision based on emerging evidence. While many studies support the use of LR-TRA for evaluation of HCC response after thermal ablation and intra-arterial embolic therapy, data suggest a need for refinements to improve assessment after radiation therapy. In this manuscript, we review expected MR imaging findings after different forms of LRT, clarify how to apply the current LI-RADS TRA by type of LRT, explore emerging literature on LI-RADS TRA, and highlight future updates to the algorithm. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

Intravascular Ultrasound-Guided Transvenous Biopsy of Retroperitoneal Lymph Nodes: Diagnostic Accuracy and Safety Compared with CT-Guided Percutaneous Biopsy.

PURPOSE: To compare the diagnostic accuracy and adverse event rates of intravascular ultrasound (US)-guided transvenous biopsy (TVB) versus those of computed tomography (CT)-guided percutaneous needle biopsy (PNB) for retroperitoneal (RP) lymph nodes. MATERIALS AND METHODS: In this single-institution, retrospective study, 32 intravascular US-guided TVB procedures and a sample of 34 CT-guided PNB procedures for RP lymph nodes where targets were deemed amenable to intravascular US-guided TVB were analyzed. Procedural metrics, including diagnostic accuracy, defined as diagnostic of malignancy or a clinically verifiable benign result, and adverse event rates were compared. RESULTS: The targets of intravascular US-guided TVB were primarily aortocaval (47%, 15/32) or precaval (34%, 11/32), whereas those of CT-guided PNB were primarily right pericaval (44%, 15/34) or retrocaval (44%, 15/34) (P < .001). The targets of intravascular US-guided TVB averaged 2.4 cm in the long axis (range, 1.3-3.7 cm) compared with 2.9 cm (range, 1.4-5.7 cm) for those of CT-guided PNB (P = .02). There was no difference in the average number of needle passes (3.8 for intravascular US-guided TVB vs 3.9 for CT-guided PNB; P = .68). The diagnostic accuracy was 94% (30/32) and the adverse event rate was 3.1% (1/32) for intravascular US-guided TVB, similar to those of CT-guided PNB (accuracy, 91% [31/34]; adverse event rate, 2.9% [1/34]). CONCLUSIONS: Intravascular US-guided TVB had a diagnostic accuracy and adverse event rate similar to CT-guided PNB for RP lymph nodes, indicating that intravascular US-guided TVB may be as safe and effective as conventional biopsy approaches for appropriately selected targets.

Intravascular Ultrasound Guidance for Transjugular Intrahepatic Portosystemic Shunt Creation Reduces Laboratory Markers of Acute Liver Injury.

PURPOSE: To compare the laboratory markers of acute liver injury after transjugular intrahepatic portosystemic shunt (TIPS) creation performed using intravascular ultrasound (IVUS) guidance with those using other techniques. MATERIALS AND METHODS: This single-center, retrospective study examined 293 TIPS procedures performed between 2014 and 2022 (160 men; mean age, 57.4 years; 71.7% with ascites, 158 with IVUS). Laboratory changes on postprocedural day (PPD) 1 were classified based on Common Terminology Criteria for Adverse Events (CTCAE) grades and were compared between IVUS and non-IVUS cases. RESULTS: IVUS cases had a lower baseline Model for End-Stage Liver Disease (MELD) score (12.5 vs 13.7, P = .016), higher pre- (16.8 vs 15.2, P = .009), and post-TIPS (6.6 vs 5.4 mm Hg, P < .001) pressure gradient, smaller stent diameter (9.2 vs 9.9 mm, P < .001), and fewer needle passes (2.4 vs 4.2, P < .001). IVUS predicted a lower PPD 1 CTCAE grade for aspartate transaminase (8.0% vs 22.2% grade ≥ 2, P = .010), alanine transaminase (ALT) (2.2% vs 7.1%, P = .017), and bilirubin (9.4% vs 26.2%, P < .001), findings confirmed using multivariable regression and propensity score analysis. IVUS predicted fewer adverse events (1.3% vs 8.1%, P = .008) and an increased likelihood of PPD 1 discharge (81% vs 59%, P = .004). IVUS was not associated with differences in PPD 30 MELD scores or 30-day survival; however, higher PPD 1 ALT (ß = 1.96, P = .008) and bilirubin levels (ß = 1.38, P = .004) predicted larger PPD 30 MELD score increase. Higher increases in ALT level predicted worse 30-day survival (hazard ratio, 1.93; P = .021). CONCLUSION: IVUS resulted in less laboratory evidence of acute liver injury immediately following TIPS creation.

Tumor size and survival in intrahepatic cholangiocarcinoma treated with surgical resection or ablation.

OBJECTIVES: We performed a retrospective analysis within a national cancer registry on outcomes following resection or ablation for intrahepatic cholangiocarcinoma (iCCA). METHODS: The National Cancer Database was queried for patients with clinical stage I-III iCCA diagnosed during 2010-2018, who underwent resection or ablation. Overall survival (OS) was compared with Kaplan-Meier and multivariable Cox proportional hazards methods. RESULTS: Of 2140 patients, 1877 (87.7%) underwent resection and 263 (12.3%) underwent ablation, with median tumor sizes of 5.5 and 3 cm, respectively. Overall, resection was associated with greater median OS (41.2 months (95% confidence interval [95% CI]: 37.6-46.2) vs. 28 months (95% CI: 15.9-28.6) on univariable analysis (p < 0.0001). There was no significant difference on multivariable analysis (p = 0.42); however, there was a significant interaction between tumor size and management. On subgroup analysis of patients with tumors <3 cm, there was no difference in OS between resection versus ablation. However, ablation was associated with increased mortality for tumors ≥3 cm. CONCLUSION: Although resection is associated with improved OS for tumors ≥3 cm, we observed no difference in survival between management strategies for tumors < 3 cm. Ablation may be an alternative therapeutic strategy for small iCCA, particularly in patients at risk for high surgical morbidity.

Clinical Predictors of a Positive Ct Angiogram Study Used for the Evaluation of Acute Gastrointestinal Hemorrhage.

BACKGROUND: Acute gastrointestinal (GI) bleeding is one of the leading causes of emergency department visits and hospital admissions. CT angiography (CTA) has had an expanding role in the evaluation of acute GI bleeding because it is rapidly performed, widely available, reasonably sensitive and provides precise localization when positive. We attempted to identify patient and clinical characteristics that predict CTA results in order to help guide the utilization of this modality in patients with acute GI bleeding. METHODS: In this retrospective study, we analyzed all CTAs performed for the evaluation of GI bleeding in the Duke University healthcare system between October 2019 and March 2020. We captured patient characteristics including age, sex, vital signs, hemoglobin, platelets, PT/INR, and anticoagulation status. Study indications were grouped by suspected source of bleeding: upper GI bleeding (hematemesis or coffee-ground emesis) vs small bowel bleeding (melena or "dark stools") vs lower GI bleeding (hematochezia or bright red blood per rectum (BRBPR)). Chi-square, Wilcoxon, t test, and multivariate logistic regression were used to describe and assess the relationship between patient characteristics and study outcomes (Table 1). Table 1 Univariate analysis of patient characteristics by CT angiography outcome Patient Characteristics by Positive CT for GI Bleed No (N = 274) Yes (N = 43) Total (N = 317) p value Gender 0.451  Female 138 (50.4%) 19 (44.2%) 157 (49.5%)  Male 136 (49.6%) 24 (55.8%) 160 (50.5%) Age, median (Q1,Q3) 65 (51,75) 70 (62,80) 66 (52, 76) < 0.012 Heart rate, median (Q1,Q3) 86 (74,100) 89 (72,98) 86 (74, 99) 0.782 MAP, mean (SD) 87.32 (15.52) 81.72 (16.53) 86.56 0.033 Shock index, median (Q1,Q3) 0.70 (0.58, 0.85) 0.78 (0.55, 1.00) 0.71 (0.58, 0.85) 0.352 Hemoglobin 0.332  N 273 43 316  Median (Q1, Q3) 8.50 (6.90, 11.00) 7.70 (6.50, 11.30) 8.45 (6.90, 11.00) Baseline hemoglobin 0.202  N 258 39 297  Median (Q1, Q3) 11.20 (9.40, 13.00) 12.00 (9.40, 14.00) 11.20 (9.40, 13.00) Hemoglobin drop from baseline 0.062  N 258 39 297  Median (Q1, Q3) 2.10 (0.60, 3.70) 2.70 (1.20, 4.80) 2.20 (0.70, 3.80) Platelets, median (Q1, Q3) 219.5 (141, 301) 183 (139, 246) 217 (139, 282) 0.102 INR 0.272  N 263 42 305  Median (Q1, Q3) 1.10 (1.00, 1.30) 1.20 (1.00, 1.30) 1.10 (1.00, 1.30) Anticoagulation 0.131  No 155 (56.6%) 19 (44.2%) 174 (54.9%)  Yes 119 (43.4%) 24 (55.8%) 143 (45.1%) Upper GI bleeding 0.401  No 251 (91.6%) 41 (95.3%) 292 (92.1%)  Yes 23 (8.4%) 2 (4.7%) 25 (7.9%) Small Bowel bleeding 0.761  No 216 (78.8%) 33 (76.7%) 249 (78.5%)  Yes 58 (21.2%) 10 (23.3%) 68 (21.5%) Lower GI bleeding 0.091  No 134 (48.9%) 15 (34.9%) 149 (47.0%)  Yes 140 (51.1%) 28 (65.1%) 168 (53.0%) 1Chi-Square 2Wilcoxon 3Equal Variance T-Test RESULTS: A total of 317 patients underwent CTA between October 2019 and March 2020. Forty-three patients (13.6%) had a CTA positive for active bleeding. Multivariable logistic regression showed that after controlling for age, mean arterial pressure (MAP) and indication, only a hemoglobin drop from baseline was significantly associated with a positive CTA. For each 1 g / dL drop in hemoglobin from the patient's baseline, the odds of a positive CT increased by 1.17 (OR 1.17 95% CI 1.00 - 1.36, p = 0.04). Age (OR 1.02 95% CI 0.99 - 1.04, p = 0.06) and hematochezia / BRBPR (OR 2.09 95% CI 0.94-4.64, p = 0.07) approached statistical significance. CONCLUSIONS: In patients who present to the hospital with GI bleeding, CTA can be a helpful triage tool that is most helpful in older patients with suspected lower GI bleeding with a drop in hemoglobin from baseline. Other clinical factors including MAP and the use of anticoagulants were not predictive of a positive CTA.

The SLC36 transporter Pathetic is required for extreme dendrite growth in Drosophila sensory neurons.

Dendrites exhibit enormous diversity in form and can differ in size by several orders of magnitude even in a single animal. However, whether neurons with large dendrite arbors have specialized mechanisms to support their growth demands is unknown. To address this question, we conducted a genetic screen for mutations that differentially affected growth in neurons with different-sized dendrite arbors. From this screen, we identified a mutant that selectively affects dendrite growth in neurons with large dendrite arbors without affecting dendrite growth in neurons with small dendrite arbors or the animal overall. This mutant disrupts a putative amino acid transporter, Pathetic (Path), that localizes to the cell surface and endolysosomal compartments in neurons. Although Path is broadly expressed in neurons and nonneuronal cells, mutation of path impinges on nutrient responses and protein homeostasis specifically in neurons with large dendrite arbors but not in other cells. Altogether, our results demonstrate that specialized molecular mechanisms exist to support growth demands in neurons with large dendrite arbors and define Path as a founding member of this growth program.

Hepatic Artery Infusion Pumps: A Surgical Toolkit for Intraoperative Decision-Making and Management of Hepatic Artery Infusion-Specific Complications.

BACKGROUND: Hepatic artery infusion (HAI) is a liver-directed therapy that delivers high-dose chemotherapy to the liver through the hepatic arterial system for colorectal liver metastases and intrahepatic cholangiocarcinoma. Utilization of HAI is rapidly expanding worldwide. OBJECTIVE AND METHODS: This review describes the conduct of HAI pump implantation, with focus on common technical pitfalls and their associated solutions. Perioperative identification and management of common postoperative complications is also described. RESULTS: HAI therapy is most commonly performed with the surgical implantation of a subcutaneous pump, and placement of its catheter into the hepatic arterial system for inline flow of pump chemotherapy directly to the liver. Intraoperative challenges and abnormal hepatic perfusion can arise due to aberrant anatomy, vascular disease, technical or patient factors. However, solutions to prevent or overcome technical pitfalls are present for the majority of cases. Postoperative HAI-specific complications arise in 22% to 28% of patients in the form of pump pocket (8%-18%), catheter (10%-26%), vascular (5%-10%), or biliary (2%-8%) complications. The majority of patients can be rescued from these complications with early identification and aggressive intervention to continue to deliver safe and effective HAI therapy. CONCLUSIONS: This HAI toolkit provides the HAI team a reference to manage commonly encountered HAI-specific perioperative obstacles and complications. Overcoming these challenges is critical to ensure safe and effective pump implantation and delivery of HAI therapy, and key to successful implementation of new programs and expansion of HAI to patients who may benefit from such a highly specialized treatment strategy.

The influence of substrate size upon pulling and gripping forces in parrots (Psittaciformes: Agapornis roseicollis).

The ability to securely grasp substrates of variable diameter is critical to arboreal animals. Arboreal specialists have emerged across several vertebrate lineages - including mammals, lizards and amphibians - and several attempts have been made to quantify their grasping performance, by measuring either gripping (i.e. forces generated about an object or substrate enclosed within the digits) or pulling (i.e. the ability to resist being removed from a substrate) forces. In this study, we present data on both pulling and gripping performance across a range of substrate diameters (0.5-17.5 mm) within a model parrot species (Agapornis roseicollis). Parrots represent an ancient arboreal lineage, allowing us to compare their abilities with those of arboreal specialists within other tetrapod groups. Data were collected using 3D-printed perches of variable diameter, and forces were registered using either an AMTI low-load force plate (grip force) or a Harvard Apparatus portable strength tester (pull force). Gripping forces peaked at a 5 mm diameter perch, while pulling forces were greatest at a 2.5 mm diameter. All forces strongly diminished above 10 mm size, suggesting grip force is optimized when utilizing small perches, a finding which corresponds to observational studies of preferential perching habits among free-ranging parrots. Relative grasping performance (adjusted for body size) in parrots is roughly equivalent to that of other arboreal specialists from other tetrapod lineages, but low when compared with that of raptorial birds that utilize their feet during aerial prey capture. Further taxonomic sampling is encouraged to contextualize how grasping performance varies in an adaptive evolutionary context.

Coaxial Stent Graft inside a Constraining Stent for Transjugular Intrahepatic Portosystemic Shunt Reduction.

A technique to create a coaxial, self-expanding stent graft inside a constraining, bare-metal, balloon-expandable stent for transjugular intrahepatic portosystemic shunt (TIPS) reduction is described. The key steps are performed on a back table rather than inside the patient, and the resulting construct is deployed using standard unsheathing maneuvers. The construct was used in 4 patients to make 6 TIPS diameter reductions (mean postreduction diameter, 6 mm; range, 0-8 mm), all resulting in increases in the portosystemic pressure gradient (mean increase, 6 mm Hg; range, 1-19 mm Hg). On average, hepatic encephalopathy improved 1 point on the West Haven scale (range, 0-2).

Safety Profile of Particle Embolization for Treatment of Acute Lower Gastrointestinal Bleeding.

PURPOSE: To assess ischemic adverse events following particle embolization when used as a second-line embolic to coil embolization for the treatment of acute lower gastrointestinal bleeding (LGIB). MATERIALS AND METHODS: The single-institution retrospective study examined 154 procedures where embolization was attempted for LGIB. In 122 patients (64 men; mean age, 69.9 years), embolization was successfully performed using microcoils in 73 procedures, particles in 34 procedures, and both microcoils and particles in 27 procedures. Particles were used as second-line only when coil embolization was infeasible or inadequate. Technical success was defined as angiographic cessation of active extravasation after embolization. Clinical success was defined as the absence of recurrent bleeding within 30 days of embolization. RESULTS: Technical success for embolization of LGIB was achieved in 87% of the cases (134/154); clinical success rate was 76.1% (102/134) among the technically successful cases. Clinical success was 82.2% (60/73) for coils alone and 68.9% (42/61) for particles with or without coils. Severe adverse events involving embolization-induced bowel ischemia occurred in 3 of 56 (5.3%) patients who underwent particle embolization with or without coils versus zero of 66 patients when coils alone were used (P = .09). In patients who had colonoscopy or bowel resection within 2 weeks of embolization, ischemic findings attributable to the procedure were found in 3 of the 15 who underwent embolization with coils alone versus 8 of 18 who underwent embolization with particles with or without coils (P = .27). CONCLUSIONS: Particle embolization for the treatment of LGIB as second-line to coil embolization was associated with a 68.9% clinical success rate and a 5.3% rate of ischemia-related adverse events.

Juxtametallic Bipolar Bone Radiofrequency Ablation: Thermal Monitoring in an Ex-Vivo Model with Specimen MRI and Histopathologic Correlation.

PURPOSE: To measure the ablation zone temperature and nontarget tissue temperature during radiofrequency (RF) ablation in bone containing metal instrumentation versus no metal instrumentation (control group). MATERIALS AND METHODS: Ex vivo experiments were performed on 15 swine vertebrae (control, n = 5; titanium screw, n = 5; stainless steel screw, n = 5). Screws and RF ablation probe were inserted identically under fluoroscopy. During RF ablation (3 W, 5 minutes), temperature was measured 10 mm from RF ablation centerpoint and in muscle contacting the screw. Magnetic resonance (MR) imaging, gross pathologic, and histopathologic analyses were performed on 1 specimen from each group. RESULTS: Ablation zone temperatures at 2.5 and 5 minutes increased by 12.2 °C ± 2.6 °C and 21.5 °C ± 2.1 °C (control); 11.0 °C ± 4.1 °C and 20.0 °C ± 2.9 °C (juxta-titanium screw), and 10.0 °C ± 3.4 °C and 17.2 °C ± 3.5 °C (juxta-stainless steel) screw; differences among groups did not reach significance by analysis of variance (P = .87). Mixed-effects linear regression revealed a statistically significant increase in temperature over time in all 3 groups (4.2 °C/min ± 0.4 °C/min, P < .001). Compared with the control, there was no significant difference in the temperature change over time for titanium (-0.3 °C/min ± 0.5 °C/min, P = .53) or steel groups (-0.4 °C/min ± 0.5 °C/min, P = .38). The mean screw temperature at the final time point did not show a statistically significant change compared with baseline in either the titanium group (-1.2 °C ± 2.3 °C, P = .50) or steel group (2.6 °C ± 2.9 °C, P = .11). MR imaging and pathologic analyses revealed homogeneous ablation without sparing of the peri-hardware zones. CONCLUSIONS: Adjacent metallic instrumentation did not affect the rate of or absolute increase in temperature in the ablation zone, did not create peri-metallic ablation inhomogeneities, and did not result in significant nontarget heating of muscle tissue in contact with the metal instrumentation.