Citations

Background Previous studies comparing a direct aspiration first pass technique (ADAPT) and stent retrievers have inconsistent methodologies and data reporting, limiting the ability to accurately assimilate data from different studies that would inform treatment of acute ischemic stroke (AIS) treatment. Objective To conduct a systematic review to discuss and compare the findings of all relevant meta-analysis studies comparing the efficacy of the ADAPT and stent retriever techniques. Methods The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), where meta-analyses comparing the efficacy of the ADAPT technique and stent retrievers in the treatment of AIS were included. We extracted all relevant data from the included studies and assessed the quality of the included meta-analyses using the Assessment of Multiple Systematic Review (AMSTAR-2). Results Seven relevant studies met our inclusion criteria and were suitable for the qualitative synthesis. All included studies obtained data from randomized controlled trials (RCTs) and observational investigations (including levels II, III, and IV). At the same time, none of them used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) for quality assessment. In accordance with AMSTAR-2, two studies were rated ‘high’, while the other five were rated ‘moderate’. Conclusions Present evidence is insufficient to clarify the superiority of one modality over the other. Further RCTs on this comparison must be conducted prior to designing further meta-analyses or making conclusive interpretations. Procedure duration and cost should be taken into consideration for any future studies.

AbstractThis second Guideline for Reasonable and Appropriate Care in the Emergency Department (GRACE‐2) from the Society for Academic Emergency Medicine is on the topic “low‐risk, recurrent abdominal pain in the emergency department.” The multidisciplinary guideline panel applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the certainty of evidence and strength of recommendations regarding four priority questions for adult emergency department patients with low‐risk, recurrent, undifferentiated abdominal pain. The intended population includes adults with multiple similar presentations of abdominal signs and symptoms recurring over a period of months or years. The panel reached the following recommendations: (1) if a prior negative computed tomography of the abdomen and pelvis (CTAP) has been performed within 12 months, there is insufficient evidence to accurately identify populations in whom repeat CTAP imaging can be safely avoided or routinely recommended; (2) if CTAP with IV contrast is negative, we suggest against ultrasound unless there is concern for pelvic or biliary pathology; (3) we suggest that screening for depression and/or anxiety may be performed during the ED evaluation; and (4) we suggest an opioid‐minimizing strategy for pain control.EXECUTIVE SUMMARYThe GRACE‐2 writing group developed clinically relevant questions to address the care of adult patients with low‐risk, recurrent, previously undifferentiated abdominal pain in the emergency department (ED). Four patient‐intervention‐comparison‐outcome‐time (PICOT) questions were developed by consensus of the writing group, who performed a systematic review of the literature and then synthesized direct and indirect evidence to formulate recommendations, following GRADE methodology. The writing group found that despite the commonality and relevance of these questions in emergency care, the quantity and quality of evidence were very limited, and even fundamental definitions of the population and outcomes of interest are lacking. Future research opportunities include developing precise and clinically relevant definitions of low‐risk, recurrent, undifferentiated abdominal pain and determining the scope of the existing populations in terms of annual national ED visits for this complaint, costs of care, and patient and provider preferences.

Abstract Rationale Cardiovascular instability/collapse is a common peri-intubation event in patients who are critically ill. Objectives To identify potentially modifiable variables associated with peri-intubation cardiovascular instability/collapse (i.e., systolic arterial pressure <65 mm Hg [once] or <90 mm Hg for >30 minutes; new/increased vasopressor requirement; fluid bolus >15 ml/kg, or cardiac arrest). Methods INTUBE (International Observational Study to Understand the Impact and Best Practices of Airway Management In Critically Ill Patients) was a multicenter prospective cohort study of patients who were critically ill and undergoing tracheal intubation in a convenience sample of 197 sites from 29 countries across five continents from October 1, 2018, to July 31, 2019. Measurements and Main Results A total of 2,760 patients were included in this analysis. Peri-intubation cardiovascular instability/collapse occurred in 1,199 out of 2,760 patients (43.4%). Variables associated with this event were older age (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.02–1.03), higher heart rate (OR, 1.008; 95% CI, 1.004–1.012), lower systolic blood pressure (OR, 0.98; 95% CI, 0.98–0.99), lower oxygen saturation as measured by pulse oximetry/Fi O2 before induction (OR, 0.998; 95% CI, 0.997–0.999), and the use of propofol as an induction agent (OR, 1.28; 95% CI, 1.05–1.57). Patients with peri-intubation cardiovascular instability/collapse were at a higher risk of ICU mortality with an adjusted OR of 2.47 (95% CI, 1.72–3.55), P < 0.001. The inverse probability of treatment weighting method identified the use of propofol as the only factor independently associated with cardiovascular instability/collapse (OR, 1.23; 95% CI, 1.02–1.49). When administered before induction, vasopressors (OR, 1.33; 95% CI, 0.84–2.11) or fluid boluses (OR, 1.17; 95% CI, 0.96–1.44) did not reduce the incidence of cardiovascular instability/collapse. Conclusions Peri-intubation cardiovascular instability/collapse was associated with an increased risk of both ICU and 28-day mortality. The use of propofol for induction was identified as a modifiable intervention significantly associated with cardiovascular instability/collapse. Clinical trial registered with clinicaltrials.gov (NCT03616054).

ABSTRACT Background Renal artery stenosis (RAS) is an important cause of chronic kidney disease and secondary hypertension. In animal models, renal ischemia leads to downregulation of growth factor expression and loss of intrarenal microcirculation. However, little is known about the sequelae of large-vessel occlusive disease on the microcirculation within human kidneys. Method This study included five patients who underwent nephrectomy due to renovascular occlusion and seven nonstenotic discarded donor kidneys (four deceased donors). Micro-computed tomography was performed to assess microvascular spatial densities and tortuosity, an index of microvascular immaturity. Renal protein expression, gene expression and histology were studied in vitro using immunoblotting, polymerase chain reaction and staining. Results RAS demonstrated a loss of medium-sized vessels (0.2–0.3 mm) compared with donor kidneys (P = 0.037) and increased microvascular tortuosity. RAS kidneys had greater protein expression of angiopoietin-1, hypoxia-inducible factor-1α and thrombospondin-1 but lower protein expression of vascular endothelial growth factor (VEGF) than donor kidneys. Renal fibrosis, loss of peritubular capillaries (PTCs) and pericyte detachment were greater in RAS, yet they had more newly formed PTCs than donor kidneys. Therefore, our study quantified significant microvascular remodeling in the poststenotic human kidney. RAS induced renal microvascular loss, vascular remodeling and fibrosis. Despite downregulated VEGF, stenotic kidneys upregulated compensatory angiogenic pathways related to angiopoietin-1. Conclusions These observations underscore the nature of human RAS as a microvascular disease distal to main vessel stenosis and support therapeutic strategies directly targeting the poststenotic kidney microcirculation in patients with RAS.

Abstract Outcomes for marginal zone lymphoma (MZL) and follicular lymphoma (FL) remain suboptimal, owing to the limited number of approved agents and the incurable nature of the diseases. BGB-3111-AU-003 was a phase 1/2, open-label, multicenter, single-agent study of the selective Bruton’s tyrosine kinase inhibitor zanubrutinib in 385 patients with B-cell malignancies. Here, we present safety and efficacy outcomes for the 53 enrolled patients with relapsed/refractory MZL (n = 20) and relapsed/refractory FL (n = 33), all of whom were enrolled during the part 2 dose expansion, and therefore received zanubrutinib at the recommended phase 2 dose. Treatment with zanubrutinib was generally well tolerated, with most adverse events being ≤ grade 2. Atrial fibrillation/flutter was not reported. Two patients required dose reduction, and 4 patients discontinued treatment because of adverse events. Response was assessed by an independent review committee for MZL and the investigators for FL, per Lugano 2014 classification for non-Hodgkin lymphoma. In patients with MZL, the overall response rate (ORR) was 80%, and the complete response (CR) rate was 20%. With median follow-up of 33.8 months, median progression-free survival (PFS) was not reached. In patients with FL, the ORR was 36.4%, and the CR rate was 18.2%. After a median follow-up of 33.9 months, median PFS was 10.4 months. In conclusion, the results of this study suggest a favorable benefit–risk profile and support zanubrutinib as a potentially meaningful addition to available therapies for patients with relapsed/refractory MZL and FL. This trial was registered at www.clinicaltrials.gov as #NCT02343120.

Human genetic studies support an inverse causal relationship between leukocyte telomere length (LTL) and coronary artery disease (CAD), but directionally mixed effects for LTL and diverse malignancies. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by expansion of hematopoietic cells bearing leukemogenic mutations, predisposes both hematologic malignancy and CAD. TERT (which encodes telomerase reverse transcriptase) is the most significantly associated germline locus for CHIP in genome-wide association studies. Here, we investigated the relationship between CHIP, LTL, and CAD in the Trans-Omics for Precision Medicine (TOPMed) program ( n = 63,302) and UK Biobank ( n = 47,080). Bidirectional Mendelian randomization studies were consistent with longer genetically imputed LTL increasing propensity to develop CHIP, but CHIP then, in turn, hastens to shorten measured LTL (mLTL). We also demonstrated evidence of modest mediation between CHIP and CAD by mLTL. Our data promote an understanding of potential causal relationships across CHIP and LTL toward prevention of CAD.

Précis: Our results suggest gonioscopy-assisted transluminal trabeculotomy (GATT) as an effective and safe option for the surgical management of open-angle glaucoma (OAG). Older age was the only risk factor for failure in our analysis. Purpose: To report 12-month clinical outcomes, safety profile and success predictors of GATT in patients with OAG. Patients and Methods: A retrospective study of patients (18 y old and above) with medically uncontrolled OAG who underwent GATT as a solo procedure or combined with phacoemulsification (PHACO-GATT) between January 2018 and January 2020. Success at 12 months (primary outcome) was defined as intraocular pressure (IOP) <15 mm Hg, with an IOP reduction of at least 20%, OR a reduction of at least 2 glaucoma medications, compared with baseline. Secondary outcomes were success predictors and safety parameters. Results: A total of 73 eyes (GATT=38; PHACO-GATT=35) from 58 patients with a mean age of 54.8±11.6 years were included. Overall, after 12 months of follow-up, the mean IOP was reduced from 24.9±8.5 to 12.1±2.1 mm Hg (P<0.001). The mean number of glaucoma medications was reduced from 3.5±0.7 to 1.2±1.2 (P<0.001). The success rate was 87% at 12 months, with no significant differences between GATT (85%) and PHACO-GATT (91%) eyes (P=0.330). Age was the only factor significantly associated with surgical success (hazard ratio=1.35; P=0.012; after adjusting for preoperative IOP and number of glaucoma medications). Patients older than 60 years had a significant greater chance of failure (hazard ratio=10.96; P=0.026) compared with those younger than 60 years. The most common postoperative complication was transient hyphema (39%; median duration, 5 d). No sight-threatening adverse event was documented. Conclusions: GATT was effective and safe at lowering IOP with or without cataract extraction in OAG. Patients 60 years or older had a higher risk of failure compared with those younger in age.