Citations

Introduction: Suction catheters and stent retrievers are based on the classical paradigm of “en bloc” removal of emboli by generation of tensile forces by vacuum or device withdrawal. However, in this process emboli elongate and fracture leading to fragmentation. Fragments can migrate downstream or remain impacted in the arterial wall resulting in a residual occlusion. Hypothesis: Clot ingestion is biomechanically superior to “en bloc” removal and leads to higher recanalization rates with less complications. Methods: To test this hypothesis, we present a hybrid test bed consisting of pressurized human brains which was developed and validated for large vessel occlusion (LVO) and revascularization. We fabricated 3 types of representative embolus analogs (EAs) (elastic, fragment-prone and stiff) and recreated 105 LVO in twenty-four fresh human brains with the vasculature connected to an hydraulic system to mimic physiological flow and pressures. Recanalization was attempted in 61 LVO cases by Direct Aspiration (DA) using an 068 catheter and in 44 LVO cases combining Stent Retriever with Aspiration (SR+A). Rates of successful recanalization (SR, Grade 2b or higher) and complete recanalization (CR, Grade 2c or higher) were measured. Up to 4 attempts were done before declaring a failure (Grade 2a or lower). Results: DA resulted in 90% of SR, 79% of CR, 61% of first pass SR and 49% of first pass CR. SR+A resulted in 34% of SR, 34% of CR, 23% of first pass SR and 14% of first pass CR. Elastic EA were associated with 88% of SR, 85% of CR, 61% of first pass SR and 52% of first pass CR. Stiff EAs were associated with 64% of SR, 64% of CR, 36% of first pass SR and 36% of first pass CR. Fragment-prone EAs were associated with 64% of SR, 40% of CR, 38% of first pass SR and 21% of first pass CR. Conclusion: Clot ingestion is biomechanically superior to “en bloc” removal and leads to the highest rates of SR, CR and first pass recanalization. DA achieves higher recanalization rates than SR+A. Elastic clots are associated with the highest rates or recanalization, followed by stiff clots and finally by fragment-prone clots.

Pre–liver transplantation (LT) renal dysfunction is associated with poor post‐LT survival. We studied whether early allograft dysfunction (EAD) modifies this association. Data on 2,856 primary LT recipients who received a transplant between 1998 and 2018 were retrospectively reviewed. Patients who died within the first post‐LT week or received multiorgan transplants and previous LT recipients were excluded. EAD was defined as (1) total bilirubin ≥ 10 mg/dL on postoperative day (POD) 7, (2) international normalized ratio ≥1.6 on POD 7, and/or (3) alanine aminotransferase or aspartate aminotransferase ≥2000 IU/mL in the first postoperative week. Pre‐LT renal dysfunction was defined as serum creatinine >1.5 mg/dL or on renal replacement therapy at LT. Patients were divided into 4 groups according to pre‐LT renal dysfunction and post‐LT EAD development. Recipients who had both pre‐LT renal dysfunction and post‐LT EAD had the worst unadjusted 1‐year, 3‐year, and 5‐year post‐LT patient and graft survival, whereas patients who had neither renal dysfunction nor EAD had the best survival (P < 0.001). After adjusting for multiple factors, the risk of death was significantly higher only in those with both pre‐LT renal dysfunction and post‐LT EAD (adjusted hazard ratio [aHR], 2.19; 95% confidence interval [CI], 1.58‐3.03; P < 0.001), whereas those with renal dysfunction and no EAD had a comparable risk of death to those with normal kidney function at LT (aHR, 1.12; 95% CI, 0.86‐1.45; P = 0.41). Results remained unchanged when pre‐LT renal dysfunction was redefined using different glomerular filtration rate cutoffs. Pre‐LT renal dysfunction negatively impacts post‐LT survival only in patients who develop EAD. Livers at higher risk of post‐LT EAD should be used with caution in recipients with pre‐LT renal dysfunction.

Abstract Lifestyle interventions are pivotal for successful management of type 2 diabetes (T2D), however, the proportion of people with T2D adhering to physical activity advice has not been thoroughly studied. The purpose of this systematic review was to summarise the evidence on adherence to exercise or physical activity components in lifestyle interventions in those with T2D. We searched MEDLINE EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and Scopus on 12 November 2019. Eligible studies enrolled adults with T2D and reported the proportion of adherence to lifestyle interventions as a primary or secondary outcome. We included 11 studies (nine randomised controlled trials (RCTs) enrolling 1717 patients and two nonrandomised studies enrolling 62 patients). Only one of the studies had low risk of bias. The proportion of participants adhering to physical activity varied from 32% to 100% with a median of 58%. Adherence was higher in interventions using supervised training and lowest in interventions using remote coaching and the adherence rate in observational studies was higher compared to RCTs (92% vs. 55%; p < 0.01). Study duration, risk of bias, or participants' sex, were not associated with adherence to physical activity. The proportion of those with T2D adhering to physical activity interventions for T2D varies widely and most of the included studies had a high risk of bias. These findings have important implications for planning and power analysis of future trials and when counselling patients about lifestyle interventions including physical activity or exercise components.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non–Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines regarding targeted therapies, immunotherapies, and their respective biomarkers.

Abstract Ultrasound localization microscopy (ULM) has been proposed to image microvasculature beyond the ultrasound diffraction limit. Although ULM can attain microvascular images with a sub-diffraction resolution, long data acquisition time and processing time are the critical limitations. Deep learning-based ULM (deep-ULM) has been proposed to mitigate these limitations. However, microbubble (MB) localization used in deep-ULMs is currently based on spatial information without the use of temporal information. The highly spatiotemporally coherent MB signals provide a strong feature that can be used to differentiate MB signals from background artifacts. In this study, a deep neural network was employed and trained with spatiotemporal ultrasound datasets to better identify the MB signals by leveraging both the spatial and temporal information of the MB signals. Training, validation and testing datasets were acquired from MB suspension to mimic the realistic intensity-varying and moving MB signals. The performance of the proposed network was first demonstrated in the chicken embryo chorioallantoic membrane dataset with an optical microscopic image as the reference standard. Substantial improvement in spatial resolution was shown for the reconstructed super-resolved images compared with power Doppler images. The full-width-half-maximum (FWHM) of a microvessel was improved from 133 μ m to 35 μ m, which is smaller than the ultrasound wavelength (73 μ m). The proposed method was further tested in an in vivo human liver data. Results showed the reconstructed super-resolved images could resolve a microvessel of nearly 170 μ m (FWHM). Adjacent microvessels with a distance of 670 μ m, which cannot be resolved with power Doppler imaging, can be well-separated with the proposed method. Improved contrast ratios using the proposed method were shown compared with that of the conventional deep-ULM method. Additionally, the processing time to reconstruct a high-resolution ultrasound frame with an image size of 1024 × 512 pixels was around 16 ms, comparable to state-of-the-art deep-ULMs.

ObjectivePatients with meniscal tears reporting meniscal symptoms such as catching or locking have traditionally undergone arthroscopy. The present study was undertaken to investigate whether patients with meniscal tears who report meniscal symptoms have greater improvement with arthroscopic partial meniscectomy (APM) than physical therapy (PT).MethodsWe used data from the Meniscal Tear in Osteoarthritis Research (MeTeOR) trial, which randomized participants with knee osteoarthritis (OA) and meniscal tear to APM or PT. The frequency of each meniscal symptom (clicking, catching, popping, intermittent locking, giving way, swelling) was measured at baseline and 6 months. We used linear regression models to determine whether the difference in improvement in Knee Injury and Osteoarthritis Outcome Score (KOOS) pain score at 6 months between patients treated with APM versus PT was modified by the presence of each meniscal symptom. We also determined the percentage of participants with resolution of meniscal symptoms by treatment group.ResultsWe included 287 participants. The presence (versus absence) of any of the meniscal symptoms did not modify the improvement in KOOS pain score between APM versus PT by >0.5 SD (all P interaction >0.05). APM led to greater resolution of intermittent locking and clicking than PT (locking 70% versus 46%, clicking 41% versus 25%). No difference in resolution of the other meniscal symptoms was observed.ConclusionMeniscal symptoms were not associated with improved pain relief. Although symptoms of clicking and intermittent locking had a greater reduction in the APM group, the presence of meniscal symptoms in isolation should not inform clinical decisions surrounding APM versus PT in patients with meniscal tear and knee OA.

Abstract Polyphenon E (Poly E) is a green tea polyphenol preparation whose most active component is epigallocatechin gallate (EGCG). We studied the cancer preventive efficacy and safety of Poly E in subjects with rectal aberrant crypt foci (ACF), which represent putative precursors of colorectal cancers. Eligible subjects had prior colorectal advanced adenomas or cancers, and had ≥5 rectal ACF at a preregistration chromoendoscopy. Subjects (N = 39) were randomized to 6 months of oral Poly E (780 mg EGCG) daily or placebo. Baseline characteristics were similar by treatment arm (all P &gt;0.41); 32 of 39 (82%) subjects completed 6 months of treatment. The primary endpoint was percent reduction in rectal ACF at chromoendoscopy comparing before and after treatment. Among 32 subjects (15 Poly E, 17 placebo), percent change in rectal ACF number (baseline vs. 6 months) did not differ significantly between study arms (3.7% difference of means; P = 0.28); total ACF burden was also similar (−2.3% difference of means; P = 0.83). Adenoma recurrence rates at 6 months were similar by arm (P &gt; 0.35). Total drug received did not differ significantly by study arm; 31 (79%) subjects received ≥70% of prescribed Poly E. Poly E was well tolerated and adverse events (AE) did not differ significantly by arm. One subject on placebo had two grade 3 AEs; one subject had grade 2 hepatic transaminase elevations attributed to treatment. In conclusion, Poly E for 6 months did not significantly reduce rectal ACF number relative to placebo. Poly E was well tolerated and without significant toxicity at the dose studied. Prevention Relevance: We report a chemoprevention trial of polyphenon E in subjects at high risk of colorectal cancer. The results show that polyphenon E was well tolerated, but did not significantly reduce the number of rectal aberrant crypt foci, a surrogate endpoint biomarker of colorectal cancer.

Abstract Background Accurate microbiologic diagnosis is important for appropriate management of infectious diseases. Sequencing-based molecular diagnostics are increasingly used for precision diagnosis of infections. However, their clinical utility is unclear. Methods We conducted a retrospective analysis of specimens that underwent 16S ribosomal RNA (rRNA) gene polymerase chain reaction (PCR) followed by Sanger sequencing at our institution from April 2017 through March 2019. Results A total of 566 specimens obtained from 460 patients were studied. Patients were considered clinically infected or noninfected based on final diagnosis and management. In 17% of patients, 16S rRNA PCR/sequencing was positive and in 5% of patients, this test led to an impact on clinical care. In comparison, bacterial cultures were positive in 21% of patients. Specimens with a positive Gram stain had 12 times greater odds of having a positive molecular result than those with a negative Gram stain (95% confidence interval for odds ratio, 5.2–31.4). Overall, PCR positivity was higher in cardiovascular specimens (37%) obtained from clinically infected patients, with bacterial cultures being more likely to be positive for musculoskeletal specimens (P &lt; .001). 16S rRNA PCR/sequencing identified a probable pathogen in 10% culture-negative specimens. Conclusion 16S rRNA PCR/sequencing can play a role in the diagnostic evaluation of patients with culture-negative infections, especially those with cardiovascular infections.

Abstract Background: We aimed to analyse clinical characteristics and find potential factors predicting poor prognosis in patients with coronavirus disease 2019 (COVID-19). Methods: We analyzed the demographic and clinical data of COVID-19 patients and detected SARS-CoV-2 RNA in urine sediments collected from 53 COVID-19 patients enrolled in Renmin Hospital of Wuhan University from January 31, 2020 to February 18, 2020 with qRT-PCR analysis, and then classified those patients based on clinical conditions (severe or non-severe syndrome) and urinary SARS-CoV-2 RNA (URNA- or URNA+). Results: We found that COVID-19 patients with severe syndrome (severe patients) showed significantly higher positive rate (11 of 23, 47.8%) of urinary SARS-CoV-2 RNA than non-severe patients (4 of 30, 13.3%, p = 0.006). URNA+ patients or severe URNA+ subgroup exhibited higher prevalence of inflammation and immune discord, cardiovascular diseases, liver damage and renal disfunction, and higher risk of death than URNA- patients. To understand the potential mechanisms underlying the viral urine shedding, we performed renal histopathological analysis on postmortems of patients with COVID-19 and found that severe renal vascular endothelium lesion characterized by increase of the expression of thrombomodulin and von Willebrand factor, markers to assess the endothelium dysfunction. We proposed a theoretical and mathematic model to depict the potential factors determining the urine shedding of SARS-CoV-2. Conclusions: This study indicated that urinary SARS-CoV-2 RNA detected in urine specimens can be used to predict the progression and prognosis of COVID-19 severity.