Zhang, Nan

Introduction: Recent studies report similar outcomes with antiplatelet drugs and intravenous thrombolysis (IVT) in patients with minor nondisabling ischemic stroke. These patients still meet emergent triage criteria and can increase the burden on stroke systems through prehospital stroke activation. Prehospital large vessel occlusion (LVO) scales can improve triage of LVO patients but have not been evaluated as tools to predict IVT administration. We sought to determine if common LVO scales can predict IVT use in a large academic telestroke practice. Methods: This retrospective study included all video telestroke consults performed in a large academic telestroke network from 2019-2020. Patients were excluded if they were on anticoagulation, presented beyond 4.5 hours from last known well, or family declined IVT due to goals of care. We recorded presenting NIHSS and IVT recommendations. NIHSS was used to calculate 7 LVO scales (RACE, G-FAST, FAST-ED, VAN, PASS, 3I-SS, and C-STAT). Scale performance was assessed by calculating area under curve (AUC) and compared to NIHSS total score using the DeLong test. Youden cutpoint was established for each scale and subsequently used to calculate sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy. Results: A total of 513 patients were included; 205/513 (40%) were recommended IVT. Median (IQR) NIHSS was 1 (0-3) in non-IVT patients and 6 (4-11) in IVT patients. The RACE and G-FAST scales were noninferior to the NIHSS in predicting IVT recommendation (Table 1). Conclusion: The RACE and G-FAST scales may be useful triage tools to identify patients needing emergent stroke evaluation for consideration of IVT.

Background: The authors examined whether ultrasound sensitivity, specificity, and accuracy in identifying intact repairs or flexor tendon gapping after zone 2 repair are affected by the number of suture strands crossing the repair or gap or imaging modality (static versus dynamic). Methods: A total of 144 fresh-frozen cadaveric digits (thumbs excluded) were randomized to either an intact repair (0-mm gap) or simulated failed repair (4-mm gap), as well as to either a two- or eight-strand locked-cruciate repair of a zone 2 flexor digitorum profundus tendon laceration using 4-0 Fiberwire. Examinations were performed by a blinded musculoskeletal ultrasonographer in static and dynamic modes using an 18-MHz transducer. Gaps were remeasured after scanning, and the final gap width recorded. McNemar exact test was used to determine whether there were differences in sensitivity, specificity, and accuracy affected by modality (static versus dynamic), and chi-square test was used to compare sensitivity, specificity, and accuracy between number of strands (two versus eight) crossing the intact repair or repair gap (≥4 mm). Results: Sensitivity, specificity, and accuracy improved with increased number of suture strands crossing the repair or gap (eight versus two), irrespective of modality (static versus dynamic), and dynamic compared with static scanning modes, irrespective of number of suture strands crossing the repair or gap site. Conclusions: The most sensitive and accurate means of assessing flexor tendon repair integrity and gapping were seen using the dynamic scanning mode. Increased number of suture strands did not negatively affect sensitivity, specificity, or accuracy, regardless of scanning mode (dynamic or static).

Introduction: Prehospital telestroke is increasingly utilized in mobile stroke units and telemedicine-enabled ambulances for acute ischemic stroke (AIS). While the NIHSS remains the standard for telestroke assessment, simpler scales have been validated to help paramedics recognize large vessel occlusion (LVO) strokes but have not been evaluated in a traditional telestroke network. We aimed to determine the accuracy of common LVO scales in a large academic telestroke practice. Methods: This retrospective study included all telestroke consults performed in a large academic telestroke network from 2019 to 2020. Patients were excluded if no NIHSS or vessel imaging was performed. We recorded presenting NIHSS, site of vessel occlusion, and discharge diagnosis. LVO was defined as an acute occlusion of the internal carotid artery and/or M1 middle cerebral artery. The NIHSS was used to calculate 7 LVO scales (RACE, C-STAT, FAST-ED, 3I-SS, PASS, VAN, and G-FAST). Diagnostic performance was assessed by calculating sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy using the established thresholds of each scale. These results were compared to NIHSS at thresholds of 6, 8, and 10. Area under curve (AUC) was calculated using c-statistics by treating scales as continuous variables. Results: A total of 625 patients were included, 373/625 (59.7%) of which were diagnosed with AIS at discharge. LVO was identified in 78/625 (12.5%) patients. VAN was the most sensitive prehospital stroke scale (83.3%), whereas 3I-SS ≥ 4 was the most specific (95.2%). Both the RACE and FAST-ED scales demonstrated superior accuracy and AUC compared to the NIHSS (Table 1). Conclusions: To our knowledge, this is the first study assessing LVO scale accuracy in a large telestroke network. As use of prehospital telestroke grows, this study highlights several scales that may allow for faster prehospital triage decisions without sacrificing accuracy.

Introduction: Telestroke facilitates emergent assessment of patients with suspected acute ischemic stroke (AIS) to identify candidates for acute interventions. The diagnostic accuracy of the telestroke consultation of a large academic hub and spoke telemedicine network has yet to be investigated. The goal of our study is to determine the diagnostic accuracy of the initial telestroke consultation. Methods: This is an IRB-exempt retrospective study including all patients evaluated for cerebral ischemia via video telestroke consultation in a large academic hub and spoke telemedicine network from 2019 to 2020. Detailed chart review was conducted to identify initial suspected diagnosis and final diagnosis. Cerebral ischemia was defined as AIS and transient ischemic attack (TIA). All other diagnoses were defined as stroke mimics. Data was organized into continuous and categorical variables. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, area under the curve (AUC) and likelihood ratio (LR+) for the initial telestroke consultation diagnosis were calculated while using the final diagnosis as the gold standard diagnosis. Results: A total of 1043 patients met inclusion criteria. Final diagnosis of cerebral ischemia was made in 63.5% of all patients (539/1043 with AIS,123/1043 with TIA). Stroke mimic was diagnosed in 36.5% patients (381/1043). The sensitivity and specificity of telestroke evaluation for diagnosis of cerebral ischemia were 97.1% and 81.4%, respectively. PPV was 90.1%, and NPV was 94.2%. Overall diagnostic accuracy was 91.4% with a LR+ of 5.21 and AUC of 0.89. The most common stroke mimics were metabolic encephalopathy (13.7%, 52/381), migraine (10.8%, 41/381) and seizure (10.5%, 40/381). Conclusions: This study highlights the high diagnostic accuracy of telestroke providers to diagnose cerebral ischemia and stroke mimic in a large academic hub and spoke network. Further research is needed to investigate methods to improve our diagnostic accuracy further, as well as explore the application of tele-neurology in the non-stroke setting.

AbstractIntroductionInfections are known complications of solid‐organ transplant. Treatment for rejection may increase risk of infection. We aimed to study frequency of infection and identify the risk factors for infections in solid organ transplant (SOT) (liver and kidney) recipients treated for rejection.MethodsThis is a retrospective chart review of all liver and kidney transplant recipients treated for rejection at our institution from 2014 to 2020. We collected information on episodes of acute rejection in the first year of transplant and infections within 6 months following rejection treatment.ResultsWe identified 257 transplant patients treated for rejection. One hundred twelve (43.6%) developed infections, with a total of 226 infections. Urinary tracts infections were the most common, 72 (31.9%), followed by cytomegalovirus viremia in 37 (16.4%), bacteremia in 24 (10.6%), and BK virus in 14 (6.2%). Female sex (p = .047), elevated neutrophil count at rejection (p = .002), and increased number of rejection episodes (p = .022) were predictors of infection in kidney and simultaneous liver‐kidney recipients. No specific type of induction or rejection therapy was identified as a risk factor for infection, likely due to the prophylaxis protocols at our institution. Infection post rejection treatment was associated with higher graft loss (p = .021) and mortality (p = .031) in kidney transplant recipients.ConclusionsInfections are common complications after treatment of SOT rejection. Female gender, higher neutrophil at time of rejection, and increased numbers of rejection episodes were predictors of infections after rejection in simultaneous liver‐kidney and kidney transplant patients. Infections were predictors of graft loss at 6 months and mortality at any point in follow‐up in kidney transplant patients. image

Abstract The purpose of this pilot study was to explore the efficacy, safety, and tolerability of vidofludimus calcium (VC) in the treatment of primary sclerosing cholangitis (PSC). This was a single‐arm open‐label pilot study with a cohort of 18 patients with PSC. Study patients received VC for a period of 6 months. The study was undertaken at two sites, Mayo Clinic, Rochester, MN, and Mayo Clinic, Phoenix, AZ. The primary endpoint of the study was improvement of serum alkaline phosphatase (ALP) at the end of the study. Secondary endpoints included assessment of other liver biomarkers (bilirubin, alanine aminotransferase, and aspartate aminotransferase). Of 18 patients enrolled, 11 completed the 6 months of study treatment. Patients who completed treatment versus those who did not were similar other than a significantly higher direct bilirubin at baseline in the group that completed treatment (mean ± SD, 0.4 ± 0.3 versus 0.1 ± 0.1, p = 0.04). By intent to treat analysis, the primary outcome was met in 16.7% (3/18) of patients. By per‐protocol analysis, including only patients who completed treatment, normalization of ALP occurred in 27.7% (3/11) at week 24 (95% confidence interval, 6.0% to 61.0%). VC was well tolerated with no drug‐related serious adverse events. Conclusion: This proof of concept study provides support for further exploration of VC in patients with PSC.

Abstract Background: Earlier cancer detection could identify tumors when they are more treatable and thus may improve clinical outcomes. A blood-based multicancer early detection test using circulating tumor cell-free DNA (cfDNA) offers the potential to address this unmet need. Our previous discovery work identified whole-genome bisulfite sequencing as outperforming whole-genome and targeted sequencing approaches for multicancer detection across stages. We thus developed a targeted methylation (TM) assay for multicancer detection and tissue-of-origin (TOO) localization. Methods: Participants were from the Circulating Cell-free Genome Atlas (CCGA; NCT02889978) and STRIVE (NCT03085888) studies, both prospective, multicenter, observational studies with longitudinal follow-up. cfDNA samples spanning >20 cancer types of all stages were divided into a cross-validated training set and an independent validation set; there were 3,583 evaluable samples in training (1,530 cancer; 2,053 noncancer) and 1,803 in validation (678 cancer; 1,125 noncancer). Performance in a prespecified set of 12 high-signal cancers was also reported (anus, bladder, colon/rectum, esophagus, head and neck, liver/bile-duct, lung, lymphoma, ovary, pancreas, plasma cell neoplasm, stomach). This multicancer early detection test evaluated cfDNA for the presence of cancer and localization of TOO; the TM classifier was trained to target >99% specificity. Precision was defined as the fraction of correct calls. Results: Participants with and without cancer were similar in age. Specificity across all cancer types in the training and validation sets was 99.8% (95% CI, 99.2-99.9%) and 99.3% (98.3-99.8%), respectively, which reflects a consistent (P=0.292) false positive rate of <1%. Across all cancer types, aggregate sensitivity was also consistent between the training and validation sets (55% [53-58%] and 55% [51-59], respectively; P=0.897). In the validation set, aggregate sensitivity in the prespecified group was 76% (73-78%); detection was 39% (27–52%) in stage I (n=62), 69% (56–80%) in stage II (n=62), 83% (75–90%) in stage III (n=102), and 92% (86–96%) in stage IV (n=130). Overall, the classifier assigned a TOO across >20 cancer types in 96% of samples (344/359); of these, the TOO was correct in 93% (321/344) of cases, which was consistent with training set analyses. Conclusions: This multicancer early detection test detected cancer signal across >20 cancer types with a single, fixed, low false positive rate and highly accurate TOO localization. Importantly, results in the independent validation set were consistent with the training set, demonstrating the robustness of machine learning classifier training, and confirms that data were not overfitted. These data support the feasibility of a single blood-based test that can detect multiple cancers, supporting further clinical development in preparation for the return of results. Citation Format: Anne-Renee Hartman, Geoffrey Oxnard, Eric Klein, Michael Seiden, Earl Hubbell, Oliver Venn, Arash Jamshidi, Nan Zhang, John Beausang, Samuel Gross, Kathryn Kurtzman, Eric Fung, Brian Allen, Alexander Fields, Hai Liu, Mikkael Sekeres, Donald Richards, Peter Yu, Alexander Aravanis, Minetta Liu. Multicancer detection of early-stage cancers with simultaneous tissue localization using a plasma cfDNA-based targeted methylation assay [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr IA02.

283 Background: Cancers of the esophagus, stomach, pancreas, gallbladder, liver, bile duct, colon and rectum will account for 17% of incident cancer diagnoses and 26% of cancer-related deaths in the US in 2019. We developed a methylation-based cfDNA early multi-cancer detection test that also can predict the tissue of origin (TOO) of these and other cancers types; performance of this test for gastrointestinal (GI) tract cancers is reported here. Methods: The Circulating Cell-free Genome Atlas (CCGA; NCT02889978) study is a prospective, multi-center, observational, case-control study with longitudinal follow-up, enrolling individuals with cancer ( > 20 cancers, all stages, newly diagnosed) and without cancer. Plasma cfDNA was subjected to a cross-validated targeted methylation (TM) sequencing assay. Methylation fragments were combined across targeted genomic regions and assigned a probability of cancer and a predicted TOO. GI cancer classes were upper GI (esophagus/stomach, n = 67), pancreas/gallbladder/extrahepatic bile duct (n = 95), liver/intrahepatic bile duct (n = 29), and colon/rectum (n = 121). Results: Detection across all GI cancers was 82% (95% CI 77-86) at a > 99% pre-set specificity. Overall predicted TOO accuracy was 92% (88-95) among the samples for which TOO was predicted (6/255 had indeterminate predicted TOO). The table shows performance by GI cancer type. Conclusions: Simultaneous detection at high specificity ( > 99%) of multiple cancer types, including GI cancers across stages at high sensitivity (82%), was shown using TM analysis of cfDNA. Accurate (92%) localization of cancers to specific regions of the GI tract was also achieved. Detection of multiple GI cancers from a single noninvasive blood test could be a practical method for detecting GI and other cancers, and may facilitate diagnostic work-ups. Clinical trial information: NCT02889978. [Table: see text]