Citations

Background Initial studies investigating correlations between stroke etiology and clot composition are conflicting and do not account for clot size as determined by area. Radiological studies have shown that cardioembolic strokes are associated with shorter clot lengths and lower clot burden than non-cardioembolic clots. Objective To report the relationship between stroke etiology, extracted clot area, and histological composition at each procedural pass. Methods As part of the multi-institutional RESTORE Registry, the Martius Scarlett Blue stained histological composition and extracted clot area of 612 per-pass clots retrieved from 441 patients during mechanical thrombectomy procedures were quantified. Correlations with clinical and procedural details were investigated. Results Clot composition varied significantly with procedural passes; clots retrieved in earlier passes had higher red blood cell content (H4=11.644, p=0.020) and larger extracted clot area (H4=10.730, p=0.030). Later passes were associated with significantly higher fibrin (H4=12.935, p=0.012) and platelets/other (H4=15.977, p=0.003) content and smaller extracted clot area. Large artery atherosclerotic (LAA) clots were significantly larger in the extracted clot area and more red blood cell-rich than other etiologies in passes 1–3. Cardioembolic and cryptogenic clots had similar histological composition and extracted clot area across all procedural passes. Conclusion LAA clots are larger and associated with a large red blood cell-rich extracted clot area, suggesting soft thrombus material. Cardioembolic clots are smaller in the extracted clot area, consistent in composition and area across passes, and have higher fibrin and platelets/other content than LAA clots, making them stiffer clots. The per-pass histological composition and extracted clot area of cryptogenic clots are similar to those of cardioembolic clots, suggesting similar formation mechanisms.

AbstractDeath with a functioning graft and death‐censored renal allograft failure remain major problems for which effective preventative protocols are lacking. The retrospective cohort study aimed to determine whether histologic changes on a 5‐year surveillance kidney biopsy predict adverse outcomes after transplantation in recipients who had: both Type 2 diabetes (T2DM) and obesity (BMI ≥ 30 kg/m2) at the time of transplantation (T2DM/Obesity, n = 75); neither (No T2DM/No obesity, n = 78); No T2DM/Obesity (n = 41), and T2DM/No obesity (n = 47). On 5‐year biopsies, moderate‐to‐severe mesangial expansion was more common in the T2DM/Obesity group (Banff mm score ≥2 = 49.3%; Tervaert classification MS ≥ 2b = 26.7%) compared to the other groups (p < .001 for both scores). Risk factors included older age, higher BMI, HbA1C, and triglycerides at 1‐year post‐transplant. Moderate‐to‐severe mesangial expansion correlated with death with function (HR 1.74 (1.01, 2.98), p = .045 Banff and 1.89 (1.01, 3.51) p = .045 Tervaert) and with death‐censored graft loss (HR 3.2 (1.2, 8.8), p = .02 Banff and HR 3.8 (1.3, 11.5), p = .01 Tervaert) over a mean of 11.6 years of recipient follow‐up post‐transplant. These data suggest that mesangial expansion in recipients with T2DM and obesity may reflect systemic vascular injury and might be a novel biomarker to predict adverse outcomes post renal transplant.

mTOR activation has been observed in rhabdomyosarcoma (RMS); however, mTOR complex (mTORC) 1 inhibition has had limited success thus far. mTOR activation alters the metabolic pathways, which is linked to survival and metastasis. These pathways have not been thoroughly analyzed in RMSs. We performed immunohistochemistry on 65 samples to analyze the expression of mTOR complexes (pmTOR, pS6, Rictor), and several metabolic enzymes (phosphofructokinase, lactate dehydrogenase-A, β-F1-ATPase, glucose-6-phosphate dehydrogenase, glutaminase). RICTOR amplification, as a potential mechanism of Rictor overexpression, was analyzed by FISH and digital droplet PCR. In total, 64% of the studied primary samples showed mTOR activity with an mTORC2 dominance (82%). Chemotherapy did not cause any relevant change in mTOR activity. Elevated mTOR activity was associated with a worse prognosis in relapsed cases. RICTOR amplification was not confirmed in any of the cases. Our findings suggest the importance of the Warburg effect and the pentose-phosphate pathway beside a glutamine demand in RMS cells. The expression pattern of the studied mTOR markers can explain the inefficacy of mTORC1 inhibitor therapy. Therefore, we suggest performing a detailed investigation of the mTOR profile before administering mTORC1 inhibitor therapy. Furthermore, our findings highlight that targeting the metabolic plasticity could be an alternative therapeutic approach.

BACKGROUND: The current coronavirus disease 2019 (COVID-19) pandemic led to a significant disruption in the care of pain from chronic and subacute conditions. The impact of this cessation of pain treatment may have unintended consequences of increased pain, reduced function, increased reliance on opioid medications, and potential increased morbidity, due to the systemic impact of untreated disease burden. This may include decreased mobility, reduction in overall health status, and increase of opioid use with the associated risks. METHODS: The article is the study of the American Society of Pain and Neuroscience (ASPN) COVID-19 task force to evaluate the policies set forth by federal, state, and local agencies to reduce or eliminate elective procedures for those patients with pain from spine, nerve, and joint disease. The impact of these decisions, which were needed to reduce the spread of the pandemic, led to a delay in care for many patients. We hence review an emergence plan to reinitiate this pain-related care. The goal is to outline a path to work with federal, state, and local authorities to combat the spread of the pandemic and minimize the deleterious impact of pain and suffering on our chronic pain patients. RESULTS: The article sets forth a strategy for the interventional pain centers to reemerge from the current pandemic and to set a course for future events. CONCLUSIONS: The COVID-19 pandemic represents an overwhelming challenge to interventional pain physicians and their patients. In addition to urgent actions needed for disease mitigation, the ASPN recommends a staged return to pain management professionals’ workflow.

AbstractObjectiveTo conduct a systematic literature review of dorsal root ganglion (DRG) stimulation for pain.DesignGrade the evidence for DRG stimulation.MethodsAn international, interdisciplinary work group conducted a literature search for DRG stimulation. Abstracts were reviewed to select studies for grading. General inclusion criteria were prospective trials (randomized controlled trials and observational studies) that were not part of a larger or previously reported group. Excluded studies were retrospective, too small, or existed only as abstracts. Studies were graded using the modified Interventional Pain Management Techniques–Quality Appraisal of Reliability and Risk of Bias Assessment, the Cochrane Collaborations Risk of Bias assessment, and the US Preventative Services Task Force level-of-evidence criteria.ResultsDRG stimulation has Level II evidence (moderate) based upon one high-quality pivotal randomized controlled trial and two lower-quality studies.ConclusionsModerate-level evidence supports DRG stimulation for treating chronic focal neuropathic pain and complex regional pain syndrome.

AbstractObjectiveTo conduct a systematic literature review of peripheral nerve stimulation (PNS) for pain.DesignGrade the evidence for PNS.MethodsAn international interdisciplinary work group conducted a literature search for PNS. Abstracts were reviewed to select studies for grading. Inclusion/exclusion criteria included prospective randomized controlled trials (RCTs) with meaningful clinical outcomes that were not part of a larger or previously reported group. Excluded studies were retrospective, had less than two months of follow-up, or existed only as abstracts. Full studies were graded by two independent reviewers using the modified Interventional Pain Management Techniques–Quality Appraisal of Reliability and Risk of Bias Assessment, the Cochrane Collaborations Risk of Bias assessment, and the US Preventative Services Task Force level-of-evidence criteria.ResultsPeripheral nerve stimulation was studied in 14 RCTs for a variety of painful conditions (headache, shoulder, pelvic, back, extremity, and trunk pain). Moderate to strong evidence supported the use of PNS to treat pain.ConclusionPeripheral nerve stimulation has moderate/strong evidence. Additional prospective trials could further refine appropriate populations and pain diagnoses.

AbstractObjectiveTo conduct a systematic literature review of spinal cord stimulation (SCS) for pain.DesignGrade the evidence for SCS.MethodsAn international, interdisciplinary work group conducted literature searches, reviewed abstracts, and selected studies for grading. Inclusion/exclusion criteria included randomized controlled trials (RCTs) of patients with intractable pain of greater than one year’s duration. Full studies were graded by two independent reviewers. Excluded studies were retrospective, had small numbers of subjects, or existed only as abstracts. Studies were graded using the modified Interventional Pain Management Techniques–Quality Appraisal of Reliability and Risk of Bias Assessment, the Cochrane Collaborations Risk of Bias assessment, and the US Preventative Services Task Force level-of-evidence criteria.ResultsSCS has Level 1 evidence (strong) for axial back/lumbar radiculopathy or neuralgia (five high-quality RCTs) and complex regional pain syndrome (one high-quality RCT).ConclusionsHigh-level evidence supports SCS for treating chronic pain and complex regional pain syndrome. For patients with failed back surgery syndrome, SCS was more effective than reoperation or medical management. New stimulation waveforms and frequencies may provide a greater likelihood of pain relief compared with conventional SCS for patients with axial back pain, with or without radicular pain.

Abstract Background: Colorectal cancer (CRC) is the second leading cause of cancer death among men and women in the United States, and additional treatment strategies are needed for patients with advanced disease. Prospective therapeutic studies based on tissue-detected genomic targets such as ERBB2 (HER2), BRAF V600E, gene rearrangements/fusions, and microsatellite instability (MSI) have demonstrated clinical benefit for mCRC patients. Although correlative studies and/or retrospective case series utilizing circulating cell-free DNA (cfDNA) next generation sequencing (NGS) have shown that plasma detection of these genomic targets shows promise in mCRC, prospective studies are lacking. We hypothesize that comprehensive genomic profiling of cfDNA will identify actionable targets and improve outcomes for patients with mCRC. Methods: COLOMATE (Colorectal Cancer and Liquid Biopsy Screening Protocol for Molecularly Assigned Therapy; NCT03765736) is a phase II umbrella screening protocol sponsored by the Academic and Community Cancer Research United (ACCRU) consortium. This study utilizes Guardant360™ (Guardant Health, Redwood City, CA) - a blood-based targeted NGS panel - to identify actionable genomic alterations in mCRC patients and to assess the impact of molecularly assigned therapy accordingly under its individual companion studies. Eligible mCRC patients must have progressed on, been intolerant to, or have a contraindication to treatment with a fluoropyrimidine, oxaliplatin, irinotecan, anti-vascular endothelial growth factor (VEGF) monoclonal antibodies (mAbs) and anti-epidermal growth factor receptor (EGFR) mAbs if RAS wild-type. Companion studies are dynamic and currently include those for patients whose tumors are either RAS/BRAF wild-type, HER2 amplified, FGFR altered, RAS mutated, or without any known actionable alteration. Additional companion studies are under active development. The primary objectives of this study are to perform blood-based genomic profiling on patients with treatment refractory mCRC to facilitate accrual to molecularly assigned therapies, and to obtain patient-matched tumor tissue and cell free DNA from peripheral blood to facilitate clinically annotated genomic analyses. Secondary correlative objectives are to explore mechanisms of acquired resistance to molecularly assigned therapy and to explore the correlation between cfDNA mutational burden (allele frequency, copy number) and clinical outcomes such as objective response rate, progression-free survival, and overall survival. Citation Format: Kristen K. Ciombor, Fang-Shu Ou, Andrew Dodge, Tyler Zemla, Christina Wu, Kimmie Ng, Katrina Pedersen, Shumei Kato, Pashtoon M. Kasi, Daniel Ahn, Rebecca Nagy, Richard Lanman, Scott Kopetz, John H. Strickler, Tanios Bekaii-Saab. COLOMATE: Colorectal cancer and liquid biopsy screening protocol for molecularly assigned therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-235.