Citations

BACKGROUND COVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined. METHODS This secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low posttransfusion antibody levels was established by 2 methods: (i) analyzing virus neutralization–equivalent anti–Spike receptor-binding domain immunoglobulin G (anti-S-RBD IgG) responses in donors or (ii) receiver operating characteristic (ROC) curve analysis. RESULTS SARS-CoV-2 anti–S-RBD IgG antibody was volume diluted 21.3-fold into posttransfusion seronegative recipients from matched donor units. Virus-specific antibody delivered was approximately 1.2 mg. The high-antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP-recipient analysis for antibody thresholds correlated to reduced hospitalizations found a statistical significant association between early transfusion and high antibodies versus all other CCP recipients (or control plasma), with antibody cutoffs established by both methods-donor-based virus neutralization cutoffs in posttransfusion recipients (0/85 [0%] versus 15/276 [5.6%]; P = 0.03) or ROC-based cutoff (0/94 [0%] versus 15/267 [5.4%]; P = 0.01). CONCLUSION In unvaccinated, seronegative CCP recipients, early transfusion of plasma units in the upper 30% of study donors’ antibody levels reduced outpatient hospitalizations. High antibody level plasma units, given early, should be reserved for therapeutic use. TRIAL REGISTRATION ClinicalTrials.gov NCT04373460. FUNDING Department of Defense (W911QY2090012); Defense Health Agency; Bloomberg Philanthropies; the State of Maryland; NIH (3R01AI152078-01S1, U24TR001609-S3, 1K23HL151826NIH); the Mental Wellness Foundation; the Moriah Fund; Octapharma; the Healthnetwork Foundation; the Shear Family Foundation; the NorthShore Research Institute; and the Rice Foundation.

Prescribed opioids are a mainstay pain treatment after traumatic injury, but a subgroup of patients may be at risk for continued opioid use. We evaluated the predictive utility of a traditional screening tool, the Opioid Risk Tool (ORT), and two other measures: average in-hospital milligram morphine equivalents (MME) per day and an assessment of opioid demand in predicting pain outcomes. Assessments of pain-related outcomes (pain intensity, interference, injury-related stress, and need for additional pain treatment) were administered at 2 weeks and 12 months post-discharge in a sample of 34 patients hospitalized for traumatic injury. Bayesian linear models were used to evaluate changes in responses over time as a function of predictors. High-risk ORT, higher MME per day, and greater opioid demand predicted less change in outcomes over time. This report provides first evidence that malleable factors of opioid and opioid demand have utility in predicting pain outcomes following traumatic injury.

Purpose To use Google trends to explore differences in public interest among types of anterior cruciate ligament (ACL) autografts, specifically quadriceps tendon, patellar tendon, and hamstring tendon autografts, between 2008 and 2019. Methods Data were obtained by querying Google Trends for key terms and phrases for online search data ranging from January 2008 to December 2019. Relative search volumes were created based on searches related to ACL reconstruction with comparative analysis generated for search terms related to quadriceps ACL, patellar tendon ACL, and hamstring ACL autografts. Statistical analysis included linear regression analysis, comparison of quarterly search volume trends over time, and comparison of cumulative annual search volumes for 2008 versus 2019. Results Linear models for respective search terms were statistically significant for the quadriceps ( P < .001) and patellar ( P = .007) tendon autograft groups but not the hamstring group ( P = .129). The quadriceps autograft group demonstrated a 12‐year search volume trend change of 0.56, which was significantly greater than the hamstring (0.07; P < .001) and patellar tendon (0.168; P < .001) groups. There was no significant difference in the trend change between hamstring and patellar tendon groups ( P = .20). Percent change in cumulative relative annual search volumes between 2008 and 2019 was 112% for the quadriceps tendon group, 12.9% for the hamstring group, and 18.6% for the patellar tendon group. Conclusions This study indicates a consistently increasing public interest in quadriceps tendon autograft for ACL reconstruction. The quadriceps autograft group demonstrated a significantly greater 12‐year online search volume, greater linear correlation, and larger percent change between 2008 and 2019 compared with patellar tendon or hamstring autograft groups. Clinical Relevance Awareness of patient perceptions has value in informing shared decision‐making, aligning patient expectations, and guiding areas of future research. Each of these has an impact on patient care. Being aware of patient interest and expectations is particularly important in areas with controversial or emerging research.

Purpose To assess outcomes of arthroscopic posterior capsular release among athletes for loss of terminal extension following anterior cruciate ligament (ACL) reconstruction. Methods A retrospective review of prospectively collected data was performed for patients undergoing arthroscopic posterior capsular release for knee extension loss following ACL reconstruction between January 2014 and December 2019. Procedure indications included extension loss greater than 10° at least 3 months after ACL reconstruction that was refractory to physical therapy. Patients were included if they were involved in either high school or college athletics, had complete outcomes of interest, and had at least 2 years of follow‐up. Prospectively collected outcomes included preoperative and postoperative measurement of knee extension, International Knee Documentation Committee score, Lysholm score, return to sport data, and complications. Results Eighteen athletes with minimum 2 years of follow‐up who underwent posterior capsular release following ACL reconstruction performed by a single surgeon were included in the analysis. Patients underwent surgery at an average of 16 weeks after ACL reconstruction. Knee extension improved an average of 13.8° at 2 years’ follow‐up (prerelease mean extension deficit 15.1°, postrelease mean extension deficit 1.3°, P < .005). Improvements in the International Knee Documentation Committee score averaged 21.7 at 6 months and 35.0 at 24 months, both of which were statistically significant ( P < .001). Similarly, differences in Lysholm included a significant improvement of 23.0 and 34.2 at 6 months and 2 years, respectively ( P < .001). In total, 77.8% returned to sport at an average of 9.8 months from their primary ACL surgery and 6.5 months following posterior capsular release surgery. No infections or neurovascular complications were observed. One patient required secondary release to achieve adequate extension. Conclusions For athletes with persistent knee extension loss after ACL reconstruction, knee extension was significantly improved at 2 years following arthroscopic posterior capsular release. Substantial improvements in patient‐reported outcomes also were seen. In addition, subjects demonstrated a high rate of return to sport and return to preinjury performance levels. Level of Evidence Level IV, therapeutic case series.

Background and Purpose The vestibular ganglion, or Scarpa’s ganglion, is a cluster of afferent vestibular neurons within the internal auditory canal (IAC). There is minimal literature describing enhancement of this region on magnetic resonance imaging (MRI) and its correlation to clinical symptoms. Here, we sought to find the prevalence of enhancement at Scarpa’s ganglion, and determine whether such enhancement correlates with demographics or clinical symptoms. Materials and Methods A retrospective review was performed of consecutive patients with an MRI of the IAC between 3/1/2021 and 5/20/2021. Two neuroradiologists independently reviewed for T1 and FLAIR enhancement of the Scarpa’s ganglion on post-contrast fat-saturated T1 and post-contrast FLAIR images. Discrepancies were agreed upon by consensus. Clinical variables (hearing loss, vestibular symptoms, tinnitus, and MRI indication) were gathered from a retrospective chart review. Results Eighty-nine patients were included (51 female); the mean age was 58 (range 19–85). The most common MRI indication was hearing loss ( n = 53). FLAIR enhancement was present on the right in 7 patients, on the left in 7 patients, and bilaterally in 6 patients. No enhancement was seen on post-contrast T1 images. There was no statistically significant correlation between consensus FLAIR on at least one side and age ( p = .74), gender ( p = .29), hearing loss ( p = .32), hearing loss side ( p = .39), type of hearing loss ( p = .87), vestibular symptoms ( p = .71), or tinnitus ( p = .81). Conclusions Enhancement is present in the minority of patients on post-contrast FLAIR images. If seen, it should be considered an uncommon but not unexpected finding with no clinical significance.

Objectives A small number of cochlear implant (CI) users experience facial nerve stimulation (FNS), which can manifest as facial twitching. In some patients, this can be resolved by adjusting the electrical stimulation parameters. However, for others, facial stimulation can significantly impair CI outcomes or even prevent its use. The exact mechanisms underlying FNS are unclear and may vary among patients. Design Transimpedance measurements were used to assess lateral and longitudinal spread of current within 15 cochlea of nucleus CI recipients with FNS (13 unilateral recipients and 1 bilateral recipient). We compared the transimpedance measurements with programming parameters from clinical visits and pre- and postoperative temporal bone computed tomography (CT) scans to identify factors that may contribute to FNS in each CI ear. Results In nine ears, transimpedance curves showed inflection, which suggests a localized current sink within the cochlea. This indicates a low-impedance pathway through which current exits the cochlea and stimulates the labyrinthine segment of the facial nerve canal. Electrodes near this current sink were disabled or underfit to minimize facial stimulation. In the other seven ears, current flow peaked toward the basal end of the cochlea, suggesting that current exits through the round window or other structures near the basal end of the cochlea, stimulating the tympanic segment of the facial nerve. Conclusions Objective transimpedance measurements can be used to elucidate the mechanisms of FNS and to develop strategies for optimizing electrical stimulation parameters and speech coding to minimize or eliminate FNS in a small subset of CI users.

Abstract Biceps tenodesis has been proven to be an effective treatment for biceps tendon and superior labral pathology. Many techniques including both open and arthroscopic approaches have been reported. Open techniques afford management of the entire proximal biceps tendon but are limited by wound healing issues, increased bleeding, and increased surgical time. Arthroscopic tenodesis offers benefits in terms of surgical efficiency, cosmesis, and bleeding risk. However, standard arthroscopic tenodesis only addresses intra‐articular biceps pathology. In this report we describe an all‐arthroscopic biceps tenodesis technique at the suprapectoral region of the humerus using knotless suture anchor fixation. Technique Video video See video under supplementary data.

AbstractBackgroundApproximately 10‐25% of amnestic early‐onset dementia are negative for amyloid (Early‐onset non‐Alzheimer’s Disease, EOnonAD). EOnonAD is a heterogenous group with various etiologies. In order to better understand the traits of EOnonAD, we clustered amnestic EOnonAD individuals according to cognitive patterns.MethodCognitive data of 62 EOnonAD individuals from the Longitudinal Early‐onset AD study (LEADS) were Z‐normalized to 91 intact individuals after adjusting for age, sex, and education. This led to domain‐averaged composite Z‐scores for memory, language, speed/attention, visuospatial, and executive function. Cluster analysis using the Ward method on the residuals for the five composites was performed. We used Scree plot using the pseudo T‐squared to determine the optimal number of clusters. We compared demographics, imaging biomarkers (amyloid and tau PET SUVR, hippocampal volume), plasma (pTau231, Aß40, Aß42, glial fibrillary acidic protein, and neurofilament light chain (NfL)), and cerebrospinal fluid (CSF) biomarkers (Aß42/40, NfL, Neurogranin, Visinin‐like protein, YKL‐40, and Synaptosome Associated Protein 25) across the clusters after adjusting for age, sex, and education. We compared gray matter density of each EOnonAD cluster to controls (n = 84) using voxel‐wise multiple linear regressions in SPM12, adjusting for age, sex, education, and intracranial volume.ResultScree plot using the pseudo‐T‐squared suggested three clusters. Cluster 1 (38/62, 61.3%) was characterized by having the mildest cognitive impairment in all domains. Cluster 2 (19/62, 30.6%) was characterized by more severe memory and language impairment. Cluster 3 (5/62, 8.1%) was characterized by more severe impairment in speed/attention, visuospatial, and executive function (Table 1). Cluster 3 showed significantly higher NfL for both plasma (Cluster 1 vs 3, p<0.001; Cluster 2 vs 3, p < 0.004) and CSF (Cluster 1 vs 3, p = 0.001). Other biomarkers did not show significant difference (Table 1). Only Cluster 3 showed significant atrophy in the bilateral fronto‐parietal areas at p<0.01, uncorrected (Figure 1).ConclusionWe identified heterogeneity in cognitive patterns among amnestic EOnonAD individuals. Cluster 1 had mildest cognitive impairment; Cluster 2 had predominant impairment in memory and language; and Cluster 3 had predominant impairment in speed/attention, visuospatial, and executive function, with significant fronto‐parietal atrophy and high NfL indicating active neurodegeneration.

BACKGROUND: Quantitative susceptibility mapping (QSM) and dynamic contrast-enhanced quantitative perfusion (DCEQP) magnetic resonance imaging sequences assessing iron deposition and vascular permeability were previously correlated with new hemorrhage in cerebral cavernous malformations. We assessed their prospective changes in a multisite trial-readiness project. METHODS: Patients with cavernous malformation and symptomatic hemorrhage (SH) in the prior year, without prior or planned lesion resection or irradiation were enrolled. Mean QSM and DCEQP of the SH lesion were acquired at baseline and at 1- and 2-year follow-ups. Sensitivity and specificity of biomarker changes were analyzed in relation to predefined criteria for recurrent SH or asymptomatic change. Sample size calculations for hypothesized therapeutic effects were conducted. RESULTS: We logged 143 QSM and 130 DCEQP paired annual assessments. Annual QSM change was greater in cases with SH than in cases without SH ( P =0.019). Annual QSM increase by ≥6% occurred in 7 of 7 cases (100%) with recurrent SH and in 7 of 10 cases (70%) with asymptomatic change during the same epoch and 3.82× more frequently than clinical events. DCEQP change had lower sensitivity for SH and asymptomatic change than QSM change and greater variance. A trial with the smallest sample size would detect a 30% difference in QSM annual change during 2 years of follow-up in 34 or 42 subjects (1 and 2 tailed, respectively); power, 0.8, α=0.05. CONCLUSIONS: Assessment of QSM change is feasible and sensitive to recurrent bleeding in cavernous malformations. Evaluation of an intervention on QSM percent change may be used as a time-averaged difference between 2 arms using a repeated measures analysis. DCEQP change is associated with lesser sensitivity and higher variability than QSM. These results are the basis of an application for certification by the US Food and Drug Administration of QSM as a biomarker of drug effect on bleeding in cavernous malformations. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03652181.