OBJECTIVE Because there is not a link between COVID-19 and pediatric hydrocephalus, the COVID-19 pandemic should not have altered the incidence of pediatric hydrocephalus or the rate of CSF diversion procedures or shunt failure. Therefore, hydrocephalus-related surgical volume should have remained constant. The goal of this study was to evaluate the rates of hydrocephalus surgeries in the COVID-19 era compared with the baseline pre-COVID-19 era. METHODS Ten institutions collected information about all hydrocephalus-related surgeries performed between March 2018 and February 2022. The period after March 1, 2020, was considered the COVID-19 era; the period prior to this date was considered the baseline pre-COVID era. Four COVID surge periods were defined using the New York Times COVID-19 database. Total case volumes were compared between the COVID era and baseline, both overall and for each surge period. Sex, race, ethnicity, insurance status, Area Deprivation Index (ADI), and rural-urban commuter area were collected for each surgery. Proportions of patients were then compared overall and for each surge based on these variables. RESULTS Of 8056 procedures, 54% were in male patients (n = 4375), 65% in White patients (n = 5247), 18% in Hispanic patients (n = 1423), and 54% in patients with public insurance (n = 4371). There was no change in the number of surgeries per site per month in the COVID era compared with baseline (16.7 vs 17.9, p = 0.113). However, there was a significant decrease in the first surge period (April 2020; 11.5 vs 17.7, p = 0.034). Male sex (p < 0.0039) and Black race (p < 0.001) were found to be associated with a significantly higher proportion of hydrocephalus procedures during the COVID-19 era. Some surge periods showed different proportions of privately insured patient and ADI levels. However, these relationships were inconsistent between surges. CONCLUSIONS Overall average monthly case numbers were not significantly different between the pre-COVID and COVID eras. There was a significant decrease in hydrocephalus surgery during the first COVID surge. More hydrocephalus surgeries were performed in children of male sex and Black race proportionally during the COVID period overall, but not during individual surges.

The neural basis of speech production involves the rapid transition from abstract planning of speech units such as syllables and phonemes, to the motor execution of speech sounds. Although a distributed network of brain regions has been implicated in speech production overall, it is unclear how the brain transitions from planning to execution for speech production. Leveraging the high spatio-temporal resolution of intracranial recordings, we find evidence for neural mechanisms that operate in space and time across the prefrontal and premotor cortices to facilitate the transition from planning to execution. During this execution, we show evidence for motor sequencing from neural activity that tracks both phonological units as well as the transition between them, suggesting both discrete elements from planning as well as continuous motor transitions. We demonstrate temporally-resolved neural mechanisms for the transition between planning and execution to facilitate speech production. ### Competing Interest Statement The authors have declared no competing interest.

Introduction: The WHO pathologic grade of meningiomas have significant prognostic and management implications, including influencing extent of surgical resection, need for postoperative radiation and frequency of postoperative surveillance imaging. Gold standard for this grading is via a time consuming, effort-intensive process driven by pathologists. We have developed a new technology, “TumorID,” which enables immediate/real-time, intraoperative tissue analysis based on laser-induced endogenous fluorescence spectroscopy ([Fig. 1]). Our aim is to apply machine learning (ML) methods to spectral emission data collected by TumorID to rapidly differentiate Grade 1 vs. Grade 2 meningiomas.

INTRODUCTION: The endoscopic third ventriculostomy (ETV) success score (ETVSS) is a useful decision-making heuristic when considering the probability of surgical success, defined as no repeat CSF diversion surgery needed within six months. Nonetheless, the original dataset published in 2009 was relatively small (n = 618) and logistic regression (LR) model performance modest. METHODS: We queried the MarketScan national database for the years 2005-2020 to identify patients <18 years of age who underwent a first-time ETV and subsequently had at least 6 months of continuous enrollment in the database. We collected data on predictors matching the original ETVSS—age, etiology of hydrocephalus, and history of any previous shunt placement. Next, we used six ML algorithms—LR, support vector classifier, random forest, k-nearest neighbors, XGBoost, and Naive Bayes—to develop predictive models. Finally, we used nested cross-validation to assess models’ comparative performances on unseen data. RESULTS: We identified 1698 patients that met inclusion criteria, and 1139 (67%) had successful ETVs. Performance of all models exceeded that of the original ETVSS, with the LR model still performing best with area under the receiver operating characteristic curve (AUROC) 0.90 (95% confidence interval, 0.86-0.94), sensitivity 0.79 (0.70-0.88), and specificity 0.91 (0.87-0.95) at Youden’s index. The random forest was the second-best ML algorithm following closely behind. This compares favorably to the original ETVSS with AUROC 0.80 (0.76-0.84, p < 0.01), sensitivity 0.65 (0.47-0.85, p < 0.01), and specificity 0.71 (0.65-0.75, p < 0.01). CONCLUSIONS: Our predictions for ETV success outperform the current gold standard. Logistic regression may still be the most interpretable and predictive algorithm; further work is underway to externally validate these models.

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Supplementary Tables1-2 from Selective Inhibition of Matrix Metalloproteinase-14 Blocks Tumor Growth, Invasion, and Angiogenesis

Supplementary Methods and Materials from Selective Inhibition of Matrix Metalloproteinase-14 Blocks Tumor Growth, Invasion, and Angiogenesis

Policies that promote conversion of antibiotics from intravenous to oral route administration are considered “low hanging fruit” for hospital antimicrobial stewardship programs. We developed a simple metric based on digestive days of therapy divided by total days of therapy for targeted agents and a method for hospital comparisons. External comparisons may help identify opportunities for improving prospective implementation.

OBJECTIVE:Posttraumatic epilepsy (PTE) develops in as many as one third of severe traumatic brain injury (TBI) patients, often years after injury. Analysis of early electroencephalographic (EEG) features, by both standardized visual interpretation (viEEG) and quantitative EEG (qEEG) analysis, may aid early identification of patients at high risk for PTE. METHODS:We performed a case-control study using a prospective database of severe TBI patients treated at a single center from 2011 to 2018. We identified patients who survived 2 years postinjury and matched patients with PTE to those without using age and admission Glasgow Coma Scale score. A neuropsychologist recorded outcomes at 1 year using the Expanded Glasgow Outcomes Scale (GOSE). All patients underwent continuous EEG for 3-5 days. A board-certified epileptologist, blinded to outcomes, described viEEG features using standardized descriptions. We extracted 14 qEEG features from an early 5-min epoch, described them using qualitative statistics, then developed two multivariable models to predict long-term risk of PTE (random forest and logistic regression). RESULTS:We identified 27 patients with and 35 without PTE. GOSE scores were similar at 1 year (p = .93). The median time to onset of PTE was 7.2 months posttrauma (interquartile range = 2.2-22.2 months). None of the viEEG features was different between the groups. On qEEG, the PTE cohort had higher spectral power in the delta frequencies, more power variance in the delta and theta frequencies, and higher peak envelope (all p < .01). Using random forest, combining qEEG and clinical features produced an area under the curve of .76. Using logistic regression, increases in the delta:theta power ratio (odds ratio [OR] = 1.3, p < .01) and peak envelope (OR = 1.1, p < .01) predicted risk for PTE. SIGNIFICANCE:In a cohort of severe TBI patients, acute phase EEG features may predict PTE. Predictive models, as applied to this study, may help identify patients at high risk for PTE, assist early clinical management, and guide patient selection for clinical trials.

INTRODUCTION: Up to one-third of severe traumatic brain injury (TBI) patients develop post-traumatic epilepsy (PTE), often years after their injury. Currently, there is no validated predictive model to identify patients at high risk for PTE. METHODS: We retrospectively analyzed a prospective database of severe TBI patients treated at a single level one trauma center from 2012 through 2018. Outcomes were recorded with the Expanded Glasgow Outcomes Scale (GOSE) at 6- and 12-months post-injury. We identified a cohort of patients who survived to two years and did not have an early post-traumatic seizure, defined as a seizure within 7 days of initial injury. From this cohort, we matched patients with PTE to those without using age and Glasgow coma scale score at admission. All patients underwent continuous EEG for 3-5 days upon admission, and a board-certified epileptologist identified 5-minute artifact-free segment for analysis. We extracted qEEG features, described them with qualitative statistics, and developed a logistic regression model using backwards selection. RESULTS: We identified 27 patients with PTE and 23 without who survived two years post-injury. The median time to onset of PTE was 7.2 months post-trauma and GOSE was similar when stratified by PTE at 6- and 12-months (p > 0.73). On qEEG analysis, patients with PTE had higher spectral power in the delta frequencies (p = 0.003), more variance in the delta and theta frequencies (p < 0.04), a higher mean amplitude (p = 0.01), and peak envelope (p = 0.01). On multivariate modeling, delta power (Odds Ratio [OR] 1.8), theta power (OR 0.2), and rhythmic spectrum (1.7) all increased risk of PTE and had an AUC of 0.85 for predicting PTE. CONCLUSIONS: In a cohort of severe TBI patients, quantitative qEEG features in the acute phase after injury identified future risk of PTE.

BACKGROUND:Shedding of Clostridioides difficile spores from infected individuals contaminates the hospital environment and contributes to infection transmission. We assessed whether antibiotic selection affects C. difficile shedding and contamination of the hospital environment. METHODS:In this prospective, unblinded, randomized controlled trial of hospitalized adults with C. difficile infection, patients were randomized 1:1:1 to receive fidaxomicin, oral vancomycin, or metronidazole. The primary outcome was change in environmental contamination rate during treatment. Secondary outcomes included stool shedding, total burden of contamination, and molecular relatedness of stool versus environmental C. difficile isolates. RESULTS:Of 33 patients enrolled, 31 (94%) completed the study. Fidaxomicin (-0.36 log10 colony-forming units [CFUs]/d [95% confidence interval (CI), -.52 to -.19]; P < .01) and vancomycin (-0.17 log10 CFUs/d [-.34 to -.01]; P = .05) were associated with more rapid decline in C. difficile shedding than metronidazole (-0.01 log10 CFUs/d [95% CI, -.10 to .08). Both vancomycin (6.3% [95% CI, 4.7-8.3) and fidaxomicin (13.1% [10.7-15.9]) were associated with lower rates of environmental contamination than metronidazole (21.4% [18.0-25.2]). With specific modeling of within-subject change over time, fidaxomicin (adjusted odds ratio, 0.83 [95% CI, .70-.99]; P = .04) was associated with more rapid decline in environmental contamination than vancomycin or metronidazole. Overall, 207 of 233 environmental C. difficile isolates (88.8%) matched patient stool isolates by ribotyping, without significant difference by treatment. CONCLUSIONS:Fidaxomicin, and to a lesser extent vancomycin, reduces C. difficile shedding and contamination of the hospital environment relative to metronidazole. Treatment choice may play a role in reducing healthcare-associated C. difficile transmission. CLINICAL TRIALS REGISTRATION:NCT02057198.

Abstract Background The impact of formalized, interdisciplinary antimicrobial stewardship program (ASP) rounds in the intensive care unit (ICU) setting has not been well described. Methods We performed a two-arm, cluster-randomized, crossover quality improvement study over 8 months to compare the impact of weekly ICU rounds with an ASP team vs. usual care. The primary outcome was antibiotic use (AU) in days of therapy (DOT) per 1,000 days present during and following ICU exposure. Our cohort consisted of ICU patients in 5 ICUs in Duke University Hospital. The unit of randomization was rounding team, which corresponded to half of the ICU beds in each unit. Each team was randomized to the intervention for 4 months followed by usual care for 4 months (or vice versa). The intervention involved multidisciplinary review of eligible patients to discuss antibiotic optimization. Patients not on antibiotics, followed by infectious diseases, post-transplant, on ECMO, or with a ventricular assist device were excluded from review. Intervention impact was assessed with multivariable negative binomial regression rate ratios (RR). AU was assessed over time before and after the study period to assess global and unit-level trends. Results We had 4,683 ICU-exposed patients. Intervention effect was not significant for the primary outcome (table). The intervention order was not significant in the model. Eligible patients were lower in the cardiothoracic ICU (CTICU) compared with other units (table); the intervention led to a significant decrease in AU when the CTICU was removed (RR = 0.93 [0.89–0.98], P = 0.0025). Intervention impact was differential among ICUs, with the greatest effect in surgical and least in CTICU (table). nit-level AU decreased in all ICUs, driven by 4 of the 5 ICUs (table, figure). Conclusion The effect of ASP rounds on AU was mixed for different types of ICUs. The direct effect on AU (intervention vs. control) was small because the analysis addressed the whole ICU population and thus was subject to biases from exposures after an ICU stay, ineligible patients, and lack of blinding. However, we observed an overall decline in AU during the study period, which we believe represents indirect effects of increased ASP activity and awareness. Additional ASP resources to round more than weekly may result in greater effect. Disclosures All Authors: No reported Disclosures.

Background Abdominal aortic aneurysm (AAA) is an important cause of mortality in older adults. The kinin B2 receptor agonist, bradykinin, has been implicated in AAA pathogenesis through promoting inflammation. Bradykinin is generated from high‐ and low‐molecular‐weight kininogen by the serine protease kallikrein‐1. The aims of this study were first to examine the effect of neutralizing kallikrein‐1 on AAA development in a mouse model and second to test how blocking kallikrein‐1 affected cyclooxygenase‐2 and prostaglandin E 2 in human AAA explants. Methods and Results Neutralization of kallikrein‐1 in apolipoprotein E‐deficient ( ApoE −/− ) mice via administration of a blocking antibody inhibited suprarenal aorta expansion in response to angiotensin (Ang) II infusion. Kallikrein‐1 neutralization decreased suprarenal aorta concentrations of bradykinin and prostaglandin E 2 and reduced cyclooxygenase‐2 activity. Kallikrein‐1 neutralization also decreased protein kinase B and extracellular signal‐regulated kinase 1/2 phosphorylation and reduced levels of active matrix metalloproteinase 2 and matrix metalloproteinase 9. Kallikrein‐1 blocking antibody reduced levels of cyclooxygenase‐2 and secretion of prostaglandin E 2 and active matrix metalloproteinase 2 and matrix metalloproteinase 9 from human AAA explants and vascular smooth muscle cells exposed to activated neutrophils. Conclusions These findings suggest that kallikrein‐1 neutralization could be a treatment target for AAA.

Ehrlichioses and anaplasmosis have undergone dramatic increases in incidence, and the geographic ranges of their occurrence and vectors have also expanded. There is marked underreporting of these diseases owing to deficient physician awareness and knowledge of the illnesses as well as limited access to appropriate diagnostic tests. Human monocytic ehrlichiosis and anaplasmosis are life threatening diseases with estimated case fatality rates of 2.7 and 0.3%, respectively. However, knowledge of their full range of signs and symptoms is incomplete, and the incidence of subclinical infections is unknown. Currently available laboratory diagnostic methods are poorly utilized, and with the exception of nucleic acid amplification tests are not useful for diagnosis during the acute stage of illness when timely treatment is needed. The Ehrlichiosis and Anaplasmosis Subcommittee of the Tick-Borne Disease Working Group recommended active clinical surveillance to determine the true incidence, full clinical spectrum, and risk factors for severe illness, as well as standardized surveillance of ticks for these pathogens, and enhanced education of primary medical caregivers and the public regarding these diseases. The subcommittee identified the needs to develop sensitive, specific acute stage diagnostic tests for local clinical laboratories and point-of-care testing, to develop approaches for utilizing electronic medical records, data mining, and artificial intelligence for assisting early diagnosis and treatment, and to develop adjunctive therapies for severe disease.

We performed a cross-sectional survey of infection preventionists in 60 US community hospitals between April 22 and May 8, 2020. Several differences in hospital preparedness for SARS-CoV-2 emerged with respect to personal protective equipment conservation strategies, protocols related to testing, universal masking, and restarting elective procedures.

We examined the microbial burden on hospital room environmental sites after standard (quaternary ammonium [Quat]) or enhanced disinfection (quat/ultraviolet light [UV-C], bleach, or bleach/UV-C). An enhanced terminal room disinfection reduced the microbial burden of epidemiologically important pathogens on high-touch surfaces in patient rooms, especially sites around the bed, better than standard room disinfection.

Background. Individual hospitals may lack expertise, data resources, and educational tools to support antimicrobial stewardship programs (ASP). Methods. We established a collaborative, consultative network focused on hospital ASP implementation. Services included on-site expert consultation, shared database for routine feedback and benchmarking, and educational programs. We performed a retrospective, longitudinal analysis of antimicrobial use (AU) in 17 hospitals that participated for at least 36 months during 2013-2018. ASP practice was assessed using structured interviews. Segmented regression estimated change in facility-wide AU after a 1-year assessment, planning, and intervention initiation period. Year 1 AU trend (1-12 months) and AU trend following the first year (13-42 months) were compared using relative rates (RR). Monthly AU rates were measured in days of therapy (DOT) per 1000 patient days for overall AU, specific agents, and agent groups. Results. Analyzed data included over 2.5 million DOT and almost 3 million patient-days. Participating hospitals increased ASPfocused activities over time. Network-wide overall AU trends were flat during the first 12 months after network entry but decreased thereafter (RR month 42 vs month 13, 0.95, 95% confidence interval [CI]:.91-.99). Large variation was seen in hospital-specific AU. Fluoroquinolone use was stable during year 1 and then dropped significantly. Other agent groups demonstrated a nonsignificant downward trajectory after year 1. Conclusions. Network hospitals increased ASP activities and demonstrated decline in AU over a 42-month period. A collaborative, consultative network is a unique model in which hospitals can access ASP implementation expertise to support long-term program growth.

Abstract Background The SARS-CoV-2 pandemic has placed a tremendous strain on the U.S. healthcare system leading to personal protective equipment (PPE) and resource shortages. Hospitals have developed contingency and crisis capacity strategies to optimize the use of resources, but, to date, community hospital preparedness has not been described. Methods We performed a cross-sectional survey of infection preventionists in 60 community hospitals within the Duke Infection Control Outreach Network between April 22 and May 7, 2020 using Qualtrics. The survey included 13 questions related to resource availability, crisis capacity strategies and approaches to testing. Results We received 50 responses during the study period with a response rate of 83%. Community hospitals reported varying degrees of PPE shortages (Table 1); 80% of community hospitals were implementing strategies to extend and reuse N95 respirators, Powered Air-Purifying Respirators, face shields and face masks. Over 70% of facilities reported reprocessing N95 respirators (Figure 1). Almost all facilities reported universal masking at time of this survey with 90% performing daily employee screening at point of entry. Additionally, 8% of facilities restarted elective procedures at the time of this survey, but only 54% of facilities reported that they were performing preoperative testing for SARS-CoV-2. Thirty-seven percent of facilities performed one SARS-CoV-2 test before discharging an asymptomatic patient to skilled nursing facility, while 43% of facilities performed 2 tests. Table 1- Supply of Personal Protective Equipment and other resources in 50 community hospitals in southeastern United States Figure 1: Different methods of reprocessing N95 respirators by 50 community hospitals in southeastern United States Conclusion Our findings reveal differences in resource availability, crisis capacity strategies and testing approaches used by community hospitals in preparation for the SARS-COV-2 pandemic. Lack of harmonization in approaches may be in part due to differences in state guidelines and decentralized federal approach to SARS-CoV-2 preparedness. Disclosures All Authors: No reported disclosures