Publications by authors named "Jennifer Kim"

241 Publications

Hospital Revisits for Post-Ischemic Stroke Epilepsy after Acute Stroke Interventions.

J Stroke Cerebrovasc Dis 2021 Oct 20;31(1):106155. Epub 2021 Oct 20.

Division of Neurocritical Care and Emergency Neurology, Department of Neurology, Yale University School of Medicine, 15 York St., LLCI Room 1004B, P.O. Box 208018, New Haven, CT 06520, USA. Electronic address:

Objectives: Improvements in acute stroke care have led to an increase in ischemic stroke survivors, who are at risk for development of post-ischemic stroke epilepsy (PISE). The impact of therapies such as thrombectomy and thrombolysis on risk of hospital revisits for PISE is unclear. We utilized administrative data to investigate the association between stroke treatment and PISE-related visits.

Materials And Methods: Using claims data from California, New York, and Florida, we performed a retrospective analysis of adult survivors of acute ischemic strokes. Patients with history of epilepsy, trauma, infections, or tumors were excluded. Included patients were followed for a primary outcome of revisits for seizures or epilepsy. Cox proportional hazards regression was used to identify covariates associated with PISE.

Results: In 595,545 included patients (median age 74 [IQR 21], 52% female), the 6-year cumulative rate of PISE-related revisit was 2.20% (95% CI 2.16-2.24). In multivariable models adjusting for demographics, comorbidities, and indicators of stroke severity, IV-tPA (HR 1.42, 95% CI 1.31-1.54, p<0.001) but not MT (HR 1.62, 95% CI 0.90-1.50, p=0.2) was associated with PISE-related revisit. Patients who underwent decompressive craniectomy experienced a 2-fold increase in odds for returning with PISE (HR 2.35, 95% CI 1.69-3.26, p<0.001). In-hospital seizures (HR 4.06, 95% CI 3.76-4.39, p<0.001) also elevated risk for PISE.

Significance: We demonstrate that ischemic stroke survivors who received IV-tPA, underwent decompressive craniectomy, or experienced acute seizures were at increased risk PISE-related revisit. Close attention should be paid to these patients with increased potential for long-term development of and re-hospitalization for PISE.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.106155DOI Listing
October 2021

A Quantitative Evaluation of Functional Recovery after Traumatic Lower Extremity Salvage.

J Surg Res 2021 Oct 10;270:85-91. Epub 2021 Oct 10.

Division of Plastic and Reconstructive Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, California. Electronic address:

Introduction: Soft tissue reconstruction is a routine component of lower extremity trauma care and focus is increasingly being directed towards understanding functional outcomes. This study aims to quantify functional recovery and identify variables associated with functional outcomes of patients who undergo traumatic limb salvage.

Methods: A retrospective review was performed of patients with lower extremity traumatic injuries requiring vascularized soft tissue reconstruction at a Level 1 trauma center between July 2007-December 2015. Postoperatively, patients were administered the 36-Item Short Form Health Survey Version 2 (SF-36v2) and the Lower Extremity Functional Scale (LEFS) questionnaires by telephone. Demographics, perioperative variables, and postoperative outcomes were analyzed by univariate and bivariate analysis.

Results: Forty-two patients with 42 flaps and a mean of 12.7 months follow up were included in the study. Limb salvage was successful in 38 patients (90.5%). Patients ≥ 40 years old had significantly worse SF-36v2 scores in physical functioning (P ≤0.01) and mental health (P ≤0.05) than their younger counterparts. Patients who had pre-existing hypertension demonstrated significantly lower physical functioning (P ≤0.01). Role limitation due to emotional health was significantly lower in patients who were female (P ≤0.01) or required revision surgery (P ≤0.01). The mean LEFS score was 37.7 ± 18.5.

Conclusions: Patients exhibited poor functional outcomes following major limb trauma with attempted limb salvage based on two validated patient reported outcomes measures (PROMs). Patient characteristics should be considered in evaluating candidates for reconstruction to optimize outcomes and to effectively counsel patients on their functional prognosis.
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http://dx.doi.org/10.1016/j.jss.2021.08.030DOI Listing
October 2021

Ocular Involvement in the Histiocytoses: A Literature Review with an Illustrative Case Series.

Ocul Immunol Inflamm 2021 Oct 12:1-15. Epub 2021 Oct 12.

Faculty of Biology, Medicine & Health, University of Manchester, Manchester, UK.

: To describe and illustrate recent reclassification and clinical descriptions of the histiocytoses, diagnosis and management, and effects on the eye and adnexae Literature review with an illustrative case series of seven patients with histiocytosis and ophthalmic involvement from a single tertiary centre. Skin lesions with signs including eyelid mass, orbital bone destruction, bizarre keratic precipitates, limbal or iris mass, haemorrhagic anterior uveitis, subretinal lesions of uncertain etiology, ischaemic retinopathy, optic neuropathy, and apparent steroid-resistant inflammations should be comprehensively investigated. Ophthalmic involvement in histiocytosis is rare. Clinical manifestations vary from limited single-organ disease to lethal systemic infiltration or malignancy. Radiology may identify lesions for biopsy. Histology with appropriate markers is essential. Oncology advice may be required.
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http://dx.doi.org/10.1080/09273948.2021.1936566DOI Listing
October 2021

Predictive model for a Rb-82 generator bolus times as a function of generator lifetime.

J Nucl Med Technol 2021 Sep 28. Epub 2021 Sep 28.

City of Hope, United States.

Rb cardiac PET is largely used to study myocardial perfusion with function, and to calculate myocardial blood flow (MBF) and coronary flow reserve (CFR) or myocardial flow reserve (MFR). Although the dosing activity of Rb is determined by the patient weight, the infusion volume and activity concentration varies with the age of the Rb generator. We sought to predict the needed bolus volume of Rb to help evaluate the accuracy of MBF findings. Data was collected from de-identified tickets of an Rb generator, including the instantaneous eluted activity flow rate. The times to reach 4 activity levels of 20, 30, 40, and 45 mCi (740, 1110, 1480, and 1665 MBq respectively) were also calculated. The activity flow rate for the largest bolus was fitted to determine the functional form. The time to reach each bolus level was fitted as a function of the generator age and 95% confidence limits were created. The activity flow rate was fitted with a growth-saturation model, allowing a calculation of bolus volume. The amplitude of the fit was observed to also be influenced by the time since last elution, and possibly other clinical factors. Elution times to reach the 4 activity levels were plotted vs. generator age. The linearized data was fitted and 95% confidence limits were created symmetrically around the fit. The 95% CL band allowed a prediction of elution time to achieve each bolus size for future generators, as a function only of generator age. A predictive model was created for elution times from this brand of Rb generator as a function of generator age. The value of this model is in determining if the necessary amount of activity can be extracted from a generator before reaching one of the backup infusion settings, such as volume limits per administration, given a generator age. Some sites may also wish to control the bolus duration for better MBF calculations, since predicting the time for the injection to complete may determine if MBF and CFR calculations are meaningful.
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http://dx.doi.org/10.2967/jnmt.120.256917DOI Listing
September 2021

The coronal plane maximum diameter of deep intracerebral hemorrhage predicts functional outcome more accurately than hematoma volume.

Int J Stroke 2021 Oct 13:17474930211050749. Epub 2021 Oct 13.

Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA.

Background: Among prognostic imaging variables, the hematoma volume on admission computed tomography (CT) has long been considered the strongest predictor of outcome and mortality in intracerebral hemorrhage.

Aims: To examine whether different features of hematoma shape are associated with functional outcome in deep intracerebral hemorrhage.

Methods: We analyzed 790 patients from the ATACH-2 trial, and 14 shape features were quantified. We calculated Spearman's Rho to assess the correlation between shape features and three-month modified Rankin scale (mRS) score, and the area under the receiver operating characteristic curve (AUC) to quantify the association between shape features and poor outcome defined as mRS>2 as well as mRS > 3.

Results: Among 14 shape features, the maximum intracerebral hemorrhage diameter in the coronal plane was the strongest predictor of functional outcome, with a maximum coronal diameter >∼3.5 cm indicating higher three-month mRS scores. The maximum coronal diameter versus hematoma volume yielded a Rho of 0.40 versus 0.35 ( = 0.006), an AUC of 0.71 versus 0.68 ( = 0.004), and an AUC of 0.71 versus 0.69 ( = 0.029). In multiple regression analysis adjusted for known outcome predictors, the maximum coronal diameter was independently associated with three-month mRS (p < 0.001).

Conclusions: A coronal-plane maximum diameter measurement offers greater prognostic value in deep intracerebral hemorrhage than hematoma volume. This simple shape metric may expedite assessment of admission head CTs, offer a potential biomarker for hematoma size eligibility criteria in clinical trials, and may substitute volume in prognostic intracerebral hemorrhage scoring systems.
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http://dx.doi.org/10.1177/17474930211050749DOI Listing
October 2021

Review of the Current Trends in Clinical Trials Involving Induced Pluripotent Stem Cells.

Stem Cell Rev Rep 2021 Sep 16. Epub 2021 Sep 16.

CiSTEM Laboratory, Catholic iPSC Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea.

In 2006, the induced pluripotent stem cell (iPSC) was presented to the world, paving the way for the development of a magnitude of novel therapeutic alternatives, addressing a diverse range of diseases. However, despite the immense cell therapy potential, relatively few clinical trials evaluating iPSC-technology have actually translated into interventional, clinically applied treatment regimens. Herein, our aim was to determine trends in globally conducted clinical trials involving iPSCs. Data were derived both from well-known registries recording clinical trials from across the globe, and databases from individual countries. Comparisons were firstly drawn between observational and interventional studies before the latter was further analyzed in terms of therapeutic and nontherapeutic trials. Our main observations included global distribution, purpose, target size, and types of disorder relevant to evaluated trials. In terms of nontherapeutic trials, the USA conducted the majority, a large average number of participants-187-was included in the trials, and studies on circulatory system disorders comprised a slightly higher proportion of total studies. Conversely, Japan was the frontrunner in terms of conducting therapeutic trials, and the average number of participants was much lower, at roughly 29. Disorders of the circulatory, as well as nervous and visual systems, were all studied in equal measure. This review highlights the impact that iPSC-based cell therapies can have, should development thereof gain more traction. We lastly considered a few companies that are actively utilizing iPSCs in the development of therapies for various diseases, for whom the global trends in clinical trials could become increasingly important.
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http://dx.doi.org/10.1007/s12015-021-10262-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445612PMC
September 2021

The Utility of Quantitative EEG in Detecting Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage.

J Clin Neurophysiol 2021 Sep 8. Epub 2021 Sep 8.

Department of Neurology, Yale University, New Haven, Connecticut, U.S.A.; and Department of Neurology, Massachussetts General Hospital, Boston, Massachussetts, U.S.A.

Summary: In this review, we discuss the utility of quantitative EEG parameters for the detection of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage in the context of the complex pathophysiology of DCI and the limitations of current diagnostic methods. Because of the multifactorial pathophysiology of DCI, methodologies solely assessing blood vessel narrowing (vasospasm) are insufficient to detect all DCI. Quantitative EEG has facilitated the exploration of EEG as a diagnostic modality of DCI. Multiple quantitative EEG parameters such as alpha power, relative alpha variability, and alpha/delta ratio show reliable detection of DCI in multiple studies. Recent studies on epileptiform abnormalities suggest that their potential for the detection of DCI. Quantitative EEG is a promising, continuous, noninvasive, monitoring modality of DCI implementable in daily practice. Future work should validate these parameters in larger populations, facilitated by the development of automated detection algorithms and multimodal data integration.
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http://dx.doi.org/10.1097/WNP.0000000000000754DOI Listing
September 2021

Focused Management of Patients With Severe Acute Brain Injury and ARDS.

Chest 2021 Sep 25. Epub 2021 Sep 25.

Department of Neurology, Yale University, New Haven, CT.

Considering the COVID-19 pandemic where concomitant occurrence of ARDS and severe acute brain injury (sABI) has increasingly coemerged, we synthesize existing data regarding the simultaneous management of both conditions. Our aim is to provide readers with fundamental principles and concepts for the management of sABI and ARDS, and highlight challenges and conflicts encountered while managing concurrent disease. Up to 40% of patients with sABI can develop ARDS. Although there are trials and guidelines to support the mainstays of treatment for ARDS and sABI independently, guidance on concomitant management is limited. Treatment strategies aimed at managing severe ARDS may at times conflict with the management of sABI. In this narrative review, we discuss the physiological basis and risks involved during simultaneous management of ARDS and sABI, summarize evidence for treatment decisions, and demonstrate these principles using hypothetical case scenarios. Use of invasive or noninvasive monitoring to assess brain and lung physiology may facilitate goal-directed treatment strategies with the potential to improve outcome. Understanding the pathophysiology and key treatment concepts for comanagement of these conditions is critical to optimizing care in this high-acuity patient population.
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http://dx.doi.org/10.1016/j.chest.2021.08.066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423666PMC
September 2021

Portable, bedside, low-field magnetic resonance imaging for evaluation of intracerebral hemorrhage.

Nat Commun 2021 08 25;12(1):5119. Epub 2021 Aug 25.

Department of Radiology, Yale University School of Medicine, New Haven, CT, USA.

Radiological examination of the brain is a critical determinant of stroke care pathways. Accessible neuroimaging is essential to detect the presence of intracerebral hemorrhage (ICH). Conventional magnetic resonance imaging (MRI) operates at high magnetic field strength (1.5-3 T), which requires an access-controlled environment, rendering MRI often inaccessible. We demonstrate the use of a low-field MRI (0.064 T) for ICH evaluation. Patients were imaged using conventional neuroimaging (non-contrast computerized tomography (CT) or 1.5/3 T MRI) and portable MRI (pMRI) at Yale New Haven Hospital from July 2018 to November 2020. Two board-certified neuroradiologists evaluated a total of 144 pMRI examinations (56 ICH, 48 acute ischemic stroke, 40 healthy controls) and one ICH imaging core lab researcher reviewed the cases of disagreement. Raters correctly detected ICH in 45 of 56 cases (80.4% sensitivity, 95%CI: [0.68-0.90]). Blood-negative cases were correctly identified in 85 of 88 cases (96.6% specificity, 95%CI: [0.90-0.99]). Manually segmented hematoma volumes and ABC/2 estimated volumes on pMRI correlate with conventional imaging volumes (ICC = 0.955, p = 1.69e-30 and ICC = 0.875, p = 1.66e-8, respectively). Hematoma volumes measured on pMRI correlate with NIH stroke scale (NIHSS) and clinical outcome (mRS) at discharge for manual and ABC/2 volumes. Low-field pMRI may be useful in bringing advanced MRI technology to resource-limited settings.
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http://dx.doi.org/10.1038/s41467-021-25441-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387402PMC
August 2021

Evaluation of A Fourth-Year Student Pharmacist Research Process in A Community Teaching Health System.

Am J Pharm Educ 2021 Jul 22:8440. Epub 2021 Jul 22.

University of North Carolina, Eshelman School of Pharmacy, Chapel Hill, North Carolina.

Doctor of pharmacy programs are encouraged to incorporate research training in their curricula, but literature is lacking describing health system student research support. The purpose of this study is to evaluate a process supporting fourth-year student pharmacist research in a health system affiliated with a school of pharmacy. In 2017, clinical non-tenure track faculty transitioned from facilitating a fourth-year research elective to implementing a new student research process which matches students to research preceptors at the beginning of the academic year and provides training and resources throughout the year. This institutional review board approved pre-post study evaluated student pharmacist research participation, dissemination, and position placement at the time of graduation, comparing 3 years before to 3 years after new process implementation. Thirty-three fourth-year students assigned to the health system graduated during 2015-2017, and 31 graduated 2018-2020. The percent of students who completed research projects increased significantly (48.5% vs 87.1%, =.0013), the number of projects increased significantly (18 vs 35, =.0047), presentations increased significantly (29 vs 63, =.0001), and publications increased numerically (9 vs 16, =.0699). Notably, the percent of research students who pursued postgraduate training increased (68.8% vs 96.3%), as well as the rate of placement into training programs (81.8% vs 92.3%); for non-research students, the percent who pursued training also increased (17.6% vs 75%), but the rate of placement remained the same (66.7%). The new fourth-year pharmacy student research process supported increased research productivity.
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http://dx.doi.org/10.5688/ajpe8440DOI Listing
July 2021

A model of metabolic supply-demand mismatch leading to secondary brain injury.

J Neurophysiol 2021 Aug 7;126(2):653-667. Epub 2021 Jul 7.

Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

Secondary brain injury (SBI) is defined as new or worsening injury to the brain after an initial neurologic insult, such as hemorrhage, trauma, ischemic stroke, or infection. It is a common and potentially preventable complication following many types of primary brain injury (PBI). However, mechanistic details about how PBI leads to additional brain injury and evolves into SBI are poorly characterized. In this work, we propose a mechanistic model for the metabolic supply demand mismatch hypothesis (MSDMH) of SBI. Our model, based on the Hodgkin-Huxley model, supplemented with additional dynamics for extracellular potassium, oxygen concentration, and excitotoxity, provides a high-level unified explanation for why patients with acute brain injury frequently develop SBI. We investigate how decreased oxygen, increased extracellular potassium, excitotoxicity, and seizures can induce SBI and suggest three underlying paths for how events following PBI may lead to SBI. The proposed model also helps explain several important empirical observations, including the common association of acute brain injury with seizures, the association of seizures with tissue hypoxia and so on. In contrast to current practices which assume that ischemia plays the predominant role in SBI, our model suggests that metabolic crisis involved in SBI can also be nonischemic. Our findings offer a more comprehensive understanding of the complex interrelationship among potassium, oxygen, excitotoxicity, seizures, and SBI. We present a novel mechanistic model for the metabolic supply demand mismatch hypothesis (MSDMH), which attempts to explain why patients with acute brain injury frequently develop seizure activity and secondary brain injury (SBI). Specifically, we investigate how decreased oxygen, increased extracellular potassium, excitotoxicity, seizures, all common sequalae of primary brain injury (PBI), can induce SBI and suggest three underlying paths for how events following PBI may lead to SBI.
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http://dx.doi.org/10.1152/jn.00674.2020DOI Listing
August 2021

Reinnervation with Selective Nerve Grafting from Multiple Donor Nerves.

Facial Plast Surg Clin North Am 2021 Aug;29(3):389-396

University Michigan Health Systems, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA. Electronic address:

Nerve substitution is an important tool in facial reanimation. The goal is to reinnervate the distal facial nerve and musculature using an alternative cranial nerve in order to achieve facial movement, symmetry, and tone. Multiple donor nerves have been used for nerve transfer procedures, the most common being hypoglossal, masseteric, and cross-facial nerve graft. Each donor nerve has its advantages and disadvantages. Multiinnervation uses the use of multiple donor nerves in order to leverage the benefits while balancing the pitfalls of each nerve. The nerve transfer depends on the type of nerve injury, time since injury, and patient factors.
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http://dx.doi.org/10.1016/j.fsc.2021.03.003DOI Listing
August 2021

The determinants of caregiver use and its costs for elderly inpatients in Korea: a study applying Andersen's behavioral model of health care utilization and replacement cost method.

BMC Health Serv Res 2021 Jul 1;21(1):631. Epub 2021 Jul 1.

Department of Preventive Medicine, College of Medicine, The Catholic University of Korea, 222-Banpo-daero, Seocho-gu, 06591, Seoul, Korea.

Objectives: The average annual healthcare expenditure among elderly patients in Korea is increasing rapidly in indirect healthcare sectors, requiring an understanding of factors related to the use of both formal and informal caregivers. This study analyzed the characteristics of caregiver use and caregiving costs among elderly patients hospitalized due to acute illness or exacerbation of chronic diseases.

Methods: A total of 819 study participants were selected from the 2017 Korea Health Panel Study Data. Replacement costing methods were applied to estimate the hours of informal caregiver assistance received by elderly inpatients. Elderly inpatients' predisposing, enabling, and need factors were studied to identify the relationship between caregiver uses, based on Andersen's behavior model. A two-part model was applied to analyze the factors related to care receipt and to estimate the incremental costs of care.

Results: Elderly inpatients who used tertiary hospitals (OR: 2.77, p-value < 0.00) and received financial support (OR: 2.68, p-value < 0.00) were more likely to receive support from a caregiver. However, elderly inpatients living alone were lesser to do so (OR: 0.49, p-value < 0.00). Elderly inpatients with Medicaid insurance (β:0.54, p-value = 0.02) or financial aid (β: 0.64, p-value < 0.00) had a statistically positive association with spending more on caregiving costs. Additionally, financial support receivers had incremental costs of $627 in caregiving costs than nonreceivers.

Conclusions: This study presented significant socioenvironmental characteristics of formal and informal caregiver use and the related expenditures. Healthcare management plans that encompass multiple social levels should be implemented to ease the caregiver burden.

Trial Registration: Retrospectively registered.
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http://dx.doi.org/10.1186/s12913-021-06677-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252285PMC
July 2021

Admission computed tomography radiomic signatures outperform hematoma volume in predicting baseline clinical severity and functional outcome in the ATACH-2 trial intracerebral hemorrhage population.

Eur J Neurol 2021 09 18;28(9):2989-3000. Epub 2021 Jul 18.

Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA.

Background And Purpose: Radiomics provides a framework for automated extraction of high-dimensional feature sets from medical images. We aimed to determine radiomics signature correlates of admission clinical severity and medium-term outcome from intracerebral hemorrhage (ICH) lesions on baseline head computed tomography (CT).

Methods: We used the ATACH-2 (Antihypertensive Treatment of Acute Cerebral Hemorrhage II) trial dataset. Patients included in this analysis (n = 895) were randomly allocated to discovery (n = 448) and independent validation (n = 447) cohorts. We extracted 1130 radiomics features from hematoma lesions on baseline noncontrast head CT scans and generated radiomics signatures associated with admission Glasgow Coma Scale (GCS), admission National Institutes of Health Stroke Scale (NIHSS), and 3-month modified Rankin Scale (mRS) scores. Spearman's correlation between radiomics signatures and corresponding target variables was compared with hematoma volume.

Results: In the discovery cohort, radiomics signatures, compared to ICH volume, had a significantly stronger association with admission GCS (0.47 vs. 0.44, p = 0.008), admission NIHSS (0.69 vs. 0.57, p < 0.001), and 3-month mRS scores (0.44 vs. 0.32, p < 0.001). Similarly, in independent validation, radiomics signatures, compared to ICH volume, had a significantly stronger association with admission GCS (0.43 vs. 0.41, p = 0.02), NIHSS (0.64 vs. 0.56, p < 0.001), and 3-month mRS scores (0.43 vs. 0.33, p < 0.001). In multiple regression analysis adjusted for known predictors of ICH outcome, the radiomics signature was an independent predictor of 3-month mRS in both cohorts.

Conclusions: Limited by the enrollment criteria of the ATACH-2 trial, we showed that radiomics features quantifying hematoma texture, density, and shape on baseline CT can provide imaging correlates for clinical presentation and 3-month outcome. These findings couldtrigger a paradigm shift where imaging biomarkers may improve current modelsfor prognostication, risk-stratification, and treatment triage of ICH patients.
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http://dx.doi.org/10.1111/ene.15000DOI Listing
September 2021

Continuous Glucose Monitoring for Underserved and Minority Patients with Type 2 Diabetes in an Interprofessional Internal Medicine Clinic.

Innov Pharm 2020 3;11(4). Epub 2020 Dec 3.

University of North Carolina Eshelman School of Pharmacy, Chapel Hill, NC.

Objective: Evaluate the impact of interprofessional continuous glucose monitoring (CGM) on glycemic control in underserved and minority patients with type 2 diabetes mellitus (T2DM).

Methods: The IRB-approved, retrospective quasi-experimental study was conducted between August 2018 and August 2019 at an internal medicine residency clinic. Adult patients with diagnosed T2DM, an indication for CGM (hyperglycemia, hypoglycemia, and/or glycemic variability), and at least 10 consecutive days of CGM data were included. Patients who were pregnant and/or missed one or more clinic appointments were excluded. Patients were followed weekly over a 14-day period during which data from the CGM sensor were downloaded and interpreted by the interprofessional team. Interventions with shared decision-making were made at each visit.

Results: Fifty-five patients were included, with a mean age of 61+11.2 years, 86% were of non-white race, and 56% were female. Average blood glucose levels decreased from 208.39 mg/dL at week 1 to 190.74 mg/dL at week 2, a 17.65 mg/dLreduction (p = 0.0281). Time within target range (70-180 mg/dL) increased by 6.16% (p = 0.0038), while time above range (>180 mg/dL) decreased by 5.5% (p = 0.0168). Average number of hypoglycemic events (readings <70 mg/dL) did not change significantly from week 1 to week 2 (2.94 vs. 3.64, p > 0.05). Of the 66 interventions made after week 1, 33% were made by the pharmacy team, 56% were made by the attending or resident physicians, and 11% were made by the dietician. Of 59 interventions made after week 2, 32% were made by the pharmacy team, 49% were made by the attending or resident physicians, and 19% were made by the dietician.

Conclusions: The interprofessional collaborative CGM service was associated with improvements in glucose control based on increased time within target range and reduced hyperglycemia, without increasing the risk of hypoglycemia or medication burden.
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http://dx.doi.org/10.24926/iip.v11i4.3501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127115PMC
December 2020

Management of thumb carpometacarpal joint dislocations: A systematic review.

J Orthop 2021 May-Jun;25:59-63. Epub 2021 Apr 1.

Department of Orthopaedic Surgery, Detroit Medical Center, Detroit, MI, 48201, USA.

Although rare, thumb Carpometacarpal (CMC) joint dislocations can have significant complications which impact hand function. Optimal management is crucial in restoring pinch and grasp strength, but no agreement exists regarding treatment due to a paucity of literature on this subject. Systematic review was conducted involving non-operative and operative management of the CMC joint. 15 articles with a total of 60 thumbs were evaluated from published literature. 12/60 thumbs with isolated CMC joint dislocations were treated with closed reduction, with 4 cases needing additional ligament repair due to joint instability post-reduction. 51/60 of the isolated CMC joint dislocations had ligament reconstruction, with flexor carpi radialis tendon autograft (29/51) as the most popular option. 60/60 patients regained full function and stability of the CMC joint with significant pain relief. Although good surgical outcomes have been achieved, long term clinical outcome reporting is needed to develop a standardized approach to treatment.
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http://dx.doi.org/10.1016/j.jor.2021.03.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065249PMC
April 2021

Steady-state kinetic analysis of halogenase-supporting flavin reductases BorF and AbeF reveals different kinetic mechanisms.

Arch Biochem Biophys 2021 06 20;704:108874. Epub 2021 Apr 20.

Department of Chemistry and Biochemistry, College of Natural Sciences and Mathematics, The University of Toledo Toledo, OH, 43606, USA. Electronic address:

The short-chain flavin reductases BorF and AbeF reduce FAD to FADH, which is then used by flavin-dependent halogenases (BorH and AbeH respectively) to regioselectively chlorinate tryptophan in the biosynthesis of indolotryptoline natural products. Recombinant AbeF and BorF were overexpressed and purified as homodimers from E. coli, and copurified with substoichiometric amounts of FAD, which could be easily removed. AbeF and BorF can reduce FAD, FMN, and riboflavin in vitro and are selective for NADH over NADPH. Initial velocity studies in the presence and absence of inhibitors showed that BorF proceeds by a sequential ordered kinetic mechanism in which FAD binds first, while AbeF follows a random-ordered sequence of substrate binding. Fluorescence quenching experiments verified that NADH does not bind BorF in the absence of FAD, and that both AbeF and BorF bind FAD with higher affinity than FADH. pH-rate profiles of BorF and AbeF were bell-shaped with maximum k at pH 7.5, and site-directed mutagenesis of BorF implicated His160 and Arg38 as contributing to the catalytic activity and the pH dependence.
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http://dx.doi.org/10.1016/j.abb.2021.108874DOI Listing
June 2021

Use of Local Anesthetic Injections in the Evaluation of Facial Synkinesis.

Facial Plast Surg Aesthet Med 2021 Apr 13. Epub 2021 Apr 13.

Department of Otolaryngology-Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA.

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http://dx.doi.org/10.1089/fpsam.2020.0582DOI Listing
April 2021

Monocyte-based inflammatory indices predict outcomes following aneurysmal subarachnoid hemorrhage.

Neurosurg Rev 2021 Apr 10. Epub 2021 Apr 10.

Department of Neurosurgery, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Phipps Building, Suite 102, Baltimore, MD, 21287, USA.

The contribution of specific immune cell populations to the post-hemorrhagic inflammatory response in aneurysmal subarachnoid hemorrhage (aSAH) and correlations with clinical outcomes, such as vasospasm and functional status, remains unclear. We aimed to compare the predictive value of leukocyte ratios that include monocytes as compared to the neutrophil-to-lymphocyte ratio (NLR) in aSAH. A prospectively accrued database of consecutive patients presenting to our institution with aSAH between January 2013 and December 2018 was used. Patients with signs and symptoms of infection (day 1-3) were excluded. Admission values of the NLR, monocyte-neutrophil-to-lymphocyte ratio (M-NLR), and lymphocyte-to-monocyte ratio (LMR) were calculated. Associations with functional status, the primary outcome, and vasospasm were evaluated using univariable and multivariable logistic regression analyses. In the cohort of 234 patients with aSAH, the M-NLR and LMR, but not the NLR, were significantly associated with poor functional status (modified Rankin scale > 2) at 12-18 months following discharge (p = 0.001, p = 0.023, p = 0.161, respectively). The area under the curve for predicting poor functional status was significantly lower for the NLR (0.543) compared with the M-NLR (0.603, p = 0.024) and LMR (0.608, p = 0.040). The M-NLR (OR = 1.01 [1.01-1.02]) and LMR (OR = 0.88 [0.78-0.99]) were independently associated with poor functional status while controlling for age, hypertension, Fisher grade, and baseline clinical status. The LMR was significantly associated with vasospasm (OR = 0.84 [0.70-0.99]) while adjusting for age, hypertension, Fisher grade, aneurysm size, and current smoking. Inflammatory indices that incorporate monocytes (e.g., M-NLR and LMR), but not those that include only neutrophils, predict outcomes after aSAH.
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http://dx.doi.org/10.1007/s10143-021-01525-1DOI Listing
April 2021

High epileptiform discharge burden predicts delayed cerebral ischemia after subarachnoid hemorrhage.

Clin Neurophysiol 2021 Mar 10. Epub 2021 Mar 10.

Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.

Objective: To investigate whether epileptiform discharge burden can identify those at risk for delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH).

Methods: Retrospective analysis of 113 moderate to severe grade SAH patients who had continuous EEG (cEEG) recordings during their hospitalization. We calculated the burden of epileptiform discharges (ED), measured as number of ED per hour.

Results: We find that many SAH patients have an increase in ED burden during the first 3-10 days following rupture, the major risk period for DCI. However, those who develop DCI have a significantly higher hourly burden from days 3.5-6 after SAH vs. those who do not. ED burden is higher in DCI patients when assessed in relation to the onset of DCI (area under the receiver operator curve 0.72). Finally, specific trends of ED burden over time, assessed by group-based trajectory analysis, also help stratify DCI risk.

Conclusions: These results suggest that ED burden is a useful parameter for identifying those at higher risk of developing DCI after SAH. The higher burden rate associated with DCI supports the theory of metabolic supply-demand mismatch which contributes to this complication.

Significance: ED burden is a novel biomarker for predicting those at high risk of DCI.
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http://dx.doi.org/10.1016/j.clinph.2021.01.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429508PMC
March 2021

Electroencephalographic Abnormalities are Common in COVID-19 and are Associated with Outcomes.

Ann Neurol 2021 05 24;89(5):872-883. Epub 2021 Mar 24.

Beth Israel Deaconess Medical Center, Department of Neurology, Harvard Medical School, Boston, MA.

Objective: The aim was to determine the prevalence and risk factors for electrographic seizures and other electroencephalographic (EEG) patterns in patients with Coronavirus disease 2019 (COVID-19) undergoing clinically indicated continuous electroencephalogram (cEEG) monitoring and to assess whether EEG findings are associated with outcomes.

Methods: We identified 197 patients with COVID-19 referred for cEEG at 9 participating centers. Medical records and EEG reports were reviewed retrospectively to determine the incidence of and clinical risk factors for seizures and other epileptiform patterns. Multivariate Cox proportional hazards analysis assessed the relationship between EEG patterns and clinical outcomes.

Results: Electrographic seizures were detected in 19 (9.6%) patients, including nonconvulsive status epilepticus (NCSE) in 11 (5.6%). Epileptiform abnormalities (either ictal or interictal) were present in 96 (48.7%). Preceding clinical seizures during hospitalization were associated with both electrographic seizures (36.4% in those with vs 8.1% in those without prior clinical seizures, odds ratio [OR] 6.51, p = 0.01) and NCSE (27.3% vs 4.3%, OR 8.34, p = 0.01). A pre-existing intracranial lesion on neuroimaging was associated with NCSE (14.3% vs 3.7%; OR 4.33, p = 0.02). In multivariate analysis of outcomes, electrographic seizures were an independent predictor of in-hospital mortality (hazard ratio [HR] 4.07 [1.44-11.51], p < 0.01). In competing risks analysis, hospital length of stay increased in the presence of NCSE (30 day proportion discharged with vs without NCSE: HR 0.21 [0.03-0.33] vs 0.43 [0.36-0.49]).

Interpretation: This multicenter retrospective cohort study demonstrates that seizures and other epileptiform abnormalities are common in patients with COVID-19 undergoing clinically indicated cEEG and are associated with adverse clinical outcomes. ANN NEUROL 2021;89:872-883.
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http://dx.doi.org/10.1002/ana.26060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104061PMC
May 2021

Addressing the Pandemic Training Deficiency: Filling the Void with Simulation in Facial Reconstruction.

Laryngoscope 2021 08 3;131(8):E2444-E2448. Epub 2021 Mar 3.

Department of Otolaryngology-Head and Neck Surgery, University of Michigan Health Systems, CS Mott Children's Hospital, Ann Arbor, Michigan, U.S.A.

Objective/hypothesis: To assess the use of a three-dimensional (3D) printed, multilayer facial flap model for use in trainee education as an alternative method of teaching surgical techniques of facial reconstruction.

Study Design: Cohort study.

Methods: A 3D printed facial flap simulator was designed from a computed tomography scan and manufactured out of silicone for low-cost, high-fidelity simulation. This simulator was tested by a group of Otolaryngology-Head and Neck Surgery trainees at a single institution. The simulator group was compared to a control group who completed an exercise on a traditional paper facial flap exercise. Both groups underwent didactic lectures prior to completing their respective exercises. Pre- and post-exercise Likert scale surveys measuring experience, understanding, effectiveness, and realism were completed by both groups. Central tendency, variability, and confidence intervals were measured to evaluate the outcomes.

Results: Trainees completing the facial flap simulator reported a statistically significant (p < 0.05) improvement in overall expertise in facial flap procedures, design of facial flaps, and excision of standing cutaneous deformities. No statistically significant improvement was seen in the control group.

Conclusions: Trainees found the facial flap simulator to be an effective and useful training tool with a high level of realism in surgical education of facial reconstruction. Surgical simulators can serve as an adjunct to trainee education, especially during extraordinary times such as the novel coronavirus disease 2019 pandemic, which significantly impacted surgical training.

Level Of Evidence: NA Laryngoscope, 131:E2444-E2448, 2021.
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http://dx.doi.org/10.1002/lary.29490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013962PMC
August 2021

Holding Out Hope After Traumatic Brain Injury.

JAMA Neurol 2021 May;78(5):522-524

Division of Neurocritical Care, Department of Neurology, Yale School of Medicine, New Haven, Connecticut.

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http://dx.doi.org/10.1001/jamaneurol.2020.5328DOI Listing
May 2021

Intervention documentation of second- to fourth-year pharmacy students during clinical experiential rotations.

Curr Pharm Teach Learn 2021 03 24;13(3):266-272. Epub 2020 Nov 24.

Pharmacy Administrative Coordinator, Cone Health, Clinical Pharmacist Practitioner, Cone Health Patient Care Center, 1200 North Elm Street, Greensboro, NC 27401, United States. Electronic address:

Introduction: The objective of this study was to evaluate pharmacy student intervention documentation during their clinical experiential rotations and to gain insight on their perceptions of this experience.

Methods: This was an institutional review board approved descriptive study of pharmacy student interventions documented during one academic year. Students documented interventions using a pharmacy-specific system in the electronic medical record. Pharmacy student feedback regarding the process and utility of intervention documentation was assessed using a brief anonymous, voluntary, three-min online survey tool.

Results: In total, 894 clinical interventions were documented by 32 students (585 by 11 fourth-year students, 309 by 21  second- and third-year students). Most interventions were categorized as other (28%), followed by change in dose, frequency or, route (26.5%). The acceptance rate was 89.5% and associated cost savings were $166,551 ($186.30 per intervention). Student survey responses were generally positive and recommended continuing the documentation process in the future.

Conclusions: This study provides insight into the concept of second- and third-year pharmacy student clinical intervention documentation, with comparison to fourth-year documentation. Future studies exploring pharmacy student intervention documentation may be valuable (e.g., expanding pharmacy services, demonstrating student impact on patient care, strategies to best facilitate learning).
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http://dx.doi.org/10.1016/j.cptl.2020.10.007DOI Listing
March 2021

Clinical use and mechanisms of resistance for PARP inhibitors in homologous recombination-deficient cancers.

Transl Oncol 2021 Mar 27;14(3):101012. Epub 2021 Jan 27.

Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States; Mays Cancer Center, UT Health San Antonio MD Anderson, San Antonio, TX, United States. Electronic address:

Cells are continuously subjected to DNA damaging agents. DNA damages are repaired by one of the many pathways guarding genomic integrity. When one or several DNA damage pathways are rendered inefficient, cells can accumulate mutations, which modify normal cellular pathways, favoring abnormal cell growth. This supports malignant transformation, which can occur when cells acquire resistance to cell cycle checkpoints, apoptosis, or growth inhibition signals. Mutations in genes involved in the repair of DNA double strand breaks (DSBs), such as BRCA1, BRCA2, or PALB2, significantly increase the risk of developing cancer of the breast, ovaries, pancreas, or prostate. Fortunately, the inability of these tumors to repair DNA breaks makes them sensitive to genotoxic chemotherapies, allowing for the development of therapies precisely tailored to individuals' genetic backgrounds. Unfortunately, as with many anti-cancer agents, drugs used to treat patients carrying a BRCA1 or BRCA2 mutation create a selective pressure, and over time tumors can become drug resistant. Here, we detail the cellular function of tumor suppressors essential in DNA damage repair pathways, present the mechanisms of action of inhibitors used to create synthetic lethality in BRCA carriers, and review the major molecular sources of drug resistance. Finally, we present examples of the many strategies being developed to circumvent drug resistance.
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http://dx.doi.org/10.1016/j.tranon.2021.101012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847957PMC
March 2021

Development of new brain metastases in triple negative breast cancer.

J Neurooncol 2021 Apr 29;152(2):333-338. Epub 2021 Jan 29.

Department of Neurosurgery, Neurosurgery Oncology, Radiation Oncology, Otolaryngology, Institute of NanoBiotechnology, The Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Phipps 123, Baltimore, MD, 21287, USA.

Background: Brain metastases are common in patients with breast cancer, and those with triple negative status have an even higher risk. Triple negative status is currently not considered when managing brain metastases.

Objective: To determine whether triple negative breast cancer (TNBC) patients with brain metastases have a higher burden of intracranial disease and whether WBRT has a survival benefit in this cohort of patients.

Methods: We conducted a retrospective cohort study with 85 patients meeting the inclusion criteria.

Results: 25% of patients had TNBC. 95% of the patients in this study received SRS and 48% received WBRT. The average number of new brain metastases from time of initial brain imaging to radiation therapy was 0.67 ± 1.1 in the non-TNBC status patients and 2.6 ± 3.7 in the triple negative status patients (p = 0.001). A cox proportional hazards model showed that WBRT does not significantly affect overall survival in patients with TNBC (HR 1.48; 95% CI 0.47-4.67; p = 0.50).

Conclusion: Our findings highlight the highly aggressive intracranial nature of TNBC. The rate of new brain metastasis formation is higher in TNBC patients compared to non-TNBC patients. Furthermore, there is no survival benefit for WBRT in TNBC patients. These findings are relevant for clinicians planning brain radiation for TNBC patients as they may find more brain metastases at the time of brain radiation than they anticipated based on initial brain imaging.
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http://dx.doi.org/10.1007/s11060-021-03702-0DOI Listing
April 2021

Health After Cancer: An Innovative Continuing Medical Education Course Integrating Cancer Survivorship Into Primary Care.

Acad Med 2021 Jan 25. Epub 2021 Jan 25.

S.M. Smith is instructor, Division of Hematology/Oncology, Department of Pediatrics, Stanford University School of Medicine, Stanford, California; ORCID: https://orcid.org/0000-0002-3369-7516. P. Williams was, at the time of this work, a research professional, Stanford Cancer Institute, Stanford, California. J. Kim is clinical assistant professor, Division of Primary Care and Population Health, Department of Medicine, Stanford, California. J. Alberto is education design and assessment associate, Continuing Medical Education, Stanford University School of Medicine, Stanford, California. L. Schapira is associate professor, Division of Medical Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, California; ORCID: http://orcid.org/0000-0003-1431-6543.

Problem: The transition from oncology care back to primary care after cancer therapy is challenging for cancer survivors who seek services that address the effect of their cancer history on their present health. Lack of knowledge about the health needs of cancer survivors is a barrier to incorporating survivorship care into primary care practice. Formal training in cancer survivorship is rarely included in medical education and presents an opportunity for intervention.

Approach: The authors developed (January 2019 - March 2020) an online continuing medical education (CME) course for primary care physicians (PCPs) that launched in April 2020. Course design and content were informed by critically reviewing cancer survivorship CME courses and understanding cancer survivors' clinical experiences in a primary care setting. The course aims to pique learners' interest through a concise, practical educational experience using peer-to-peer primary care-focused instruction in a case-based, multimedia-enriched format. In the course, 4 patient cases illustrate the physical and psychological effects of cancer treatment, and a primary care narrator demonstrates ways to approach these concerns during a clinic visit, providing tips for empathic communication with cancer survivors. The course development team-including a PCP, medical and pediatric oncologists, and medical educators with expertise in instructional design-used an iterative process to review and revise the content. PCPs and specialists reviewed the script and provided constructive feedback that was incorporated into revisions.

Outcomes: The authors will evaluate course effectiveness based upon user experience and perceived effect on clinical practice and professional growth. A follow-up survey will assess barriers to course completion and durability of effect.

Next Steps: Future directions include dissemination of the course to a broader audience including medical trainees, evaluation of higher-level learning outcomes (e.g., effect on PCPs' clinical practice), and adaptation of the course for patients with a focus on self-management.
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http://dx.doi.org/10.1097/ACM.0000000000003935DOI Listing
January 2021

Electroencephalography, Hospital Complications, and Longitudinal Outcomes After Subarachnoid Hemorrhage.

Neurocrit Care 2021 Jan 22. Epub 2021 Jan 22.

Department of Neurology, Massachusetts General Hospital, 55 Fruit Street, Lunder 644, Boston, MA, 02114, USA.

Background: Following non-traumatic subarachnoid hemorrhage (SAH), in-hospital delayed cerebral ischemia is predicted by two chief events on continuous EEG (cEEG): new or worsening epileptiform abnormalities (EAs) and deterioration of cEEG background frequencies. We evaluated the association between longitudinal outcomes and these cEEG biomarkers. We additionally evaluated the association between longitudinal outcomes and other in-hospital complications.

Methods: Patients with nontraumatic SAH undergoing ≥ 3 days of cEEG monitoring were enrolled in a prospective study evaluating longitudinal outcomes. Modified Rankin Scale (mRS) was assessed at discharge, and at 3- and 6-month follow-up time points. Adjusting for baseline severity in a cumulative proportional odds model, we modeled the mRS ordinally and measured the association between mRS and two forms of in-hospital cEEG deterioration: (1) cEEG evidence of new or worsening epileptiform abnormalities and (2) cEEG evidence of new background deterioration. We compared the magnitude of these associations at each time point with the association between mRS and other in-hospital complications: (1) delayed cerebral ischemia (DCI), (2) hospital-acquired infections (HAI), and (3) hydrocephalus. In a secondary analysis, we employed a linear mixed effects model to examine the association of mRS over time (dichotomized as 0-3 vs. 4-6) with both biomarkers of cEEG deterioration and with other in-hospital complications.

Results: In total, 175 mRS assessments were performed in 59 patients. New or worsening EAs developed in 23 (39%) patients, and new background deterioration developed in 24 (41%). Among cEEG biomarkers, new or worsening EAs were independently associated with mRS at discharge, 3, and 6 months, respectively (adjusted cumulative proportional odds 4.99, 95% CI 1.60-15.6; 3.28, 95% CI 1.14-9.5; and 2.71, 95% CI 0.95-7.76), but cEEG background deterioration lacked an association. Among hospital complications, DCI was associated with discharge, 3-, and 6-month outcomes (adjusted cumulative proportional odds 4.75, 95% CI 1.64-13.8; 3.4; 95% CI 1.24-9.01; and 2.45, 95% CI 0.94-6.6), but HAI and hydrocephalus lacked an association. The mixed effects model demonstrated that these associations were sustained over longitudinal assessments without an interaction with time.

Conclusion: Although new or worsening EAs and cEEG background deterioration have both been shown to predict DCI, only new or worsening EAs are associated with a sustained impairment in functional outcome. This novel finding raises the potential for identifying therapeutic targets that may also influence outcomes.
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http://dx.doi.org/10.1007/s12028-020-01177-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822587PMC
January 2021

Vessel wall MRI in ruptured cranial dural arteriovenous fistulas.

Interv Neuroradiol 2021 Aug 11;27(4):553-557. Epub 2021 Jan 11.

Department of Neurosurgery, Yale University School of Medicine, New Haven, USA.

Intracranial high-resolution vessel wall MRI (VW-MRI) is an imaging paradigm that is useful in site-of-rupture identification in patients presenting with spontaneous subarachnoid hemorrhage and multiple intracranial aneurysms. Only a handful of case reports describe its potential utility in the evaluation of more complex brain vascular malformations. We report for the first time three patients with ruptured cranial dural arteriovenous fistulas (dAVFs) that were evaluated with high-resolution VW-MRI. The presumed site-of-rupture was identified based on contiguity of a venous ectasia with adjacent blood products and thick, concentric wall enhancement. This preliminary experience suggests a role for high-resolution VW-MRI in the evaluation of ruptured cranial dAVFs, in particular, site-of-rupture identification. It also supports an emerging hypothesis that all spontaneously ruptured, macrovascular lesions demonstrate avid vessel wall enhancement.
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http://dx.doi.org/10.1177/1591019920988205DOI Listing
August 2021

A review of indications and comorbidities in which warfarin may be the preferred oral anticoagulant.

J Clin Pharm Ther 2021 Jun 4;46(3):560-570. Epub 2021 Jan 4.

Cone Health Department of Internal Medicine, Greensboro, NC, USA.

What Is Known And Objective: Direct oral anticoagulants (DOACs) are increasingly prescribed instead of warfarin for chronic anticoagulation for ease of dosing, fewer interactions, and less stringent monitoring. However, it is important to consider indications and comorbidities for which warfarin is still the preferred anticoagulant. This review aims to capture these clinical scenarios in which warfarin may still be preferred over DOACs.

Methods: We undertook a comprehensive literature search using the PubMed database. Key search terms were based on DOAC clinical trial exclusion criteria, as well as indications and conditions in which the use of DOACs for anticoagulation has suggested harm. Society guidelines and tertiary literature were used to inform expert opinion where necessary. Studies were included if they investigated the use of DOACs or warfarin in the identified indications or conditions.

Results And Discussion: Currently, evidence for the use of warfarin over DOACs for anticoagulation is strongest for patients with prosthetic valves, antiphospholipid syndrome, or a high risk of gastrointestinal bleeding. For several clinical situations, including mitral stenosis, obesity, altered gastrointestinal anatomy, pulmonary arterial hypertension, renal or hepatic impairment, and left ventricular thrombus, evidence is lacking but may eventually support the use of DOACs. Depending on indication and condition, appropriateness of DOAC use may vary by agent.

What Is New And Conclusion: New evidence continues to support new indications and conditions in which DOACs may be appropriate to use for anticoagulation. There are key clinical scenarios, however, in which emerging literature continues to support warfarin as the preferred anticoagulant.
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http://dx.doi.org/10.1111/jcpt.13343DOI Listing
June 2021
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