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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.

Background: Propofol is a key component for the management of sedation and shivering during targeted temperature management (TTM) following cardiac arrest. The cardiac depressant effects of propofol have not been described during TTM and may be especially relevant given the stress to the myocardium following cardiac arrest. The purpose of this study is to describe hemodynamic changes associated with propofol administration during TTM. Methods: This single center, retrospective cohort study evaluated adult patients who received a propofol infusion for at least 30 minutes during TTM. The primary outcome was the change in cardiovascular Sequential Organ Failure Assessment (cvSOFA) score 30 minutes after propofol initiation. Secondary outcomes included change in systolic blood pressure (SBP), mean arterial pressure (MAP), heart rate (HR), and vasopressor requirements (VR) expressed as norepinephrine equivalents at 30, 60, 120, 180, and 240 minutes after propofol initiation. A multivariate regression was performed to assess the influence of propofol and body temperature on MAP, while controlling for vasopressor dose and cardiac arrest hospital prognosis (CAHP) score. Results: The cohort included 40 patients with a median CAHP score of 197. The goal temperature of 33°C was achieved for all patients. The median cvSOFA score was 1 at baseline and 0.5 at 30 minutes, with a non-significant change after propofol initiation ( P = .96). SBP and MAP reductions were the greatest at 60 minutes (17 and 8 mmHg; P

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.

Graphical Abstract 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. Supplementary Information The online version contains supplementary material available at 10.1007/s12015-021-10262-3.

Background: There is abundant and even confusing information in the available literature concerning the role of internal limiting membrane (ILM) removal in macular conditions secondary to non-complicated macula-off rhegmatogenous retinal detachment (RRD) repair. This retrospective, multicenter, long-term study aimed to analyze the incidence of epiretinal membrane (ERM) proliferation and other surgical complications and to compare the postoperative microstructural and multimodal imaging findings and correlate them with the final postoperative best-corrected visual acuity (BCVA) in selected eyes.

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. NEW & NOTEWORTHY 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.

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.

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., Conventional magnetic resonance imaging (MRI) operates at a high magnetic field strength and requires a strict access-controlled environment, making MRI often inaccessible. Here, the authors present a portable low-field MRI device that detects intracerebral hemorrhage with high accuracy.

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

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.

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.

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

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. Electronic supplementary material The online version of this article (10.1007/s12028-020-01177-x) contains supplementary material, which is available to authorized users.

Background. Fertility preservation (FP) prior to gonadotoxic cancer treatment is underutilized in the United States (US) due to limited access to care. Objective. We aimed to determine the utilization of a regional FP program in an underserved region in the Southeast US. Methods. We performed an institutional review board-approved retrospective cohort study of patients enrolled in the FP program at an academic tertiary medical center from 2014 to 2018. Results. Sixty-nine reproductive age patients were enrolled in the FP program, including 29 men and 40 women between 20 and 49 years of age. Cancer diagnoses among the enrolled patients included hematologic (n = 34), breast (n = 14), testicular (n = 11), reproductive tract (n = 7), and gastrointestinal (n = 3) malignancies. Patients with reproductive tract malignancies were found to have approximately 9.7 times greater odds of proceeding with FP than patients with hematologic malignancies (P Conclusion. Utilization of a regional FP program should be considered to increase access to care to this critical resource for patients desiring future family building. Patients with hematologic malignancy may face unique barriers to FP.

Background and ObjectivesDelayed cerebral ischemia (DCI) is the leading complication of subarachnoid hemorrhage (SAH). Because DCI was traditionally thought to be caused by large vessel vasospasm, transcranial Doppler ultrasounds (TCDs) have been the standard of care. Continuous EEG has emerged as a promising complementary monitoring modality and predicts increased DCI risk. Our objective was to determine whether combining EEG and TCD data improves prediction of DCI after SAH. We hypothesize that integrating these diagnostic modalities improves DCI prediction.MethodsWe retrospectively assessed patients with moderate to severe SAH (2011–2015; Fisher 3–4 or Hunt-Hess 4–5) who had both prospective TCD and EEG acquisition during hospitalization. Middle cerebral artery (MCA) peak systolic velocities (PSVs) and the presence or absence of epileptiform abnormalities (EAs), defined as seizures, epileptiform discharges, and rhythmic/periodic activity, were recorded daily. Logistic regressions were used to identify significant covariates of EAs and TCD to predict DCI. Group-based trajectory modeling (GBTM) was used to account for changes over time by identifying distinct group trajectories of MCA PSV and EAs associated with DCI risk.ResultsWe assessed 107 patients; DCI developed in 56 (51.9%). Univariate predictors of DCI are presence of high-MCA velocity (PSV ≥200 cm/s, sensitivity 27%, specificity 89%) and EAs (sensitivity 66%, specificity 62%) on or before day 3. Two univariate GBTM trajectories of EAs predicted DCI (sensitivity 64%, specificity 62.75%). Logistic regression and GBTM models using both TCD and EEG monitoring performed better. The best logistic regression and GBTM models used both TCD and EEG data, Hunt-Hess score at admission, and aneurysm treatment as predictors of DCI (logistic regression: sensitivity 90%, specificity 70%; GBTM: sensitivity 89%, specificity 67%).DiscussionEEG and TCD biomarkers combined provide the best prediction of DCI. The conjunction of clinical variables with the timing of EAs and high MCA velocities improved model performance. These results suggest that TCD and cEEG are promising complementary monitoring modalities for DCI prediction. Our model has potential to serve as a decision support tool in SAH management.Classification of EvidenceThis study provides Class II evidence that combined TCD and EEG monitoring can identify delayed cerebral ischemia after SAH.

ObjectiveTo determine whether race is associated with the development of epilepsy after subdural hematoma (SDH), we identified adult survivors of SDH in a statewide administrative dataset and followed them up for at least 1 year for revisits associated with epilepsy.MethodsWe performed a retrospective cohort study using claims data on all discharges from emergency departments (EDs) and hospitals in California. We identified adults (age ≥18 years) admitted from 2005 to 2011 with first-time traumatic and nontraumatic SDH. We used validated diagnosis codes to identify a primary outcome of ED or inpatient revisit for epilepsy. We used multivariable Cox regression for survival analysis to identify demographic and medical risk factors for epilepsy.ResultsWe identified 29,342 survivors of SDH (mean age 71.2 [SD 16.4] years, female sex 11,954 [41.1%]). Three thousand two hundred thirty (11.0%) patients had revisits to EDs or hospitals with a diagnosis of epilepsy during the study period. Black patients (n = 1,684 [5.7%]) had significantly increased risk compared to White patients (n = 16,945 [57.7%]; hazard ratio [HR] 1.45, 95% confidence interval [CI] 1.28–1.64, p < 0.001). Status epilepticus during the index SDH admission, although infrequent (n = 94 [0.3%]), was associated with a nearly 4-fold risk of epilepsy (HR 3.75, 95% CI 2.80–5.03, p < 0.001). Alcohol use, drug use, smoking, renal disease, and markers of injury severity (i.e., intubation, surgical intervention, length of stay, disposition other than home) were also associated with epilepsy (all p < 0.05).ConclusionsWe found an association between Black race and ED and hospital revisits for epilepsy after SDH, establishing the presence of a racial subgroup that is particularly vulnerable to post-SDH epileptogenesis.

CASE SUMMARY A 28-year-old nulliparous woman presented with rectal bleeding. Colonoscopy revealed a 4-cm malignant-appearing mass in the proximal rectum, and biopsies confirmed invasive adenocarcinoma of the rectum. Computed tomography scan showed no evidence of metastatic disease. Staging MRI found transmural extension with minimal stranding in the adjacent fat, as well as no evidence of pathological pelvic adenopathy, consistent with a T3N0 lesion. The proposed treatment plan involved neoadjuvant chemotherapy and radiation therapy before primary surgical resection. The patient desired fertility preservation and was referred immediately to Reproductive Endocrinology and Infertility. She underwent assisted reproduction with oocyte and blastocyst cryopreservation followed by laparoscopic ovarian transposition. Nine months after surgical low anterior resection of the tumor and completion of her cancer treatment, her ovaries were repositioned to their normal pelvic position during an ileostomy takedown procedure. She underwent a frozen embryo transfer but did not conceive. She resumed menses and later conceived spontaneously. Her pregnancy was complicated by cervical incompetence, requiring cervical cerclage. She delivered a live male infant via cesarean delivery at 32 weeks gestation, approximately 2 years after completion of cancer therapy. Four years after diagnosis, the patient remains in remission with undetectable CEA levels.

Background and Purpose— We evaluated the association between 2 types of predictors of delayed cerebral ischemia after nontraumatic subarachnoid hemorrhage, including biomarkers of the innate immune response and neurophysiologic changes on continuous electroencephalography. Methods— We studied subarachnoid hemorrhage patients that had at least 72 hours of continuous electroencephalography and blood samples collected within the first 5 days of symptom onset. We measured inflammatory biomarkers previously associated with delayed cerebral ischemia and functional outcome, including soluble ST2 (sST2), IL-6 (interleukin-6), and CRP (C-reactive protein). Serial plasma samples and cerebrospinal fluid sST2 levels were available in a subgroup of patients. Neurophysiologic changes were categorized into new or worsening epileptiform abnormalities (EAs) or new background deterioration. The association of biomarkers with neurophysiologic changes were evaluated using the Wilcoxon rank-sum test. Plasma and cerebrospinal fluid sST2 were further examined longitudinally using repeated measures mixed-effects models. Results— Forty-six patients met inclusion criteria. Seventeen (37%) patients developed new or worsening EAs, 21 (46%) developed new background deterioration, and 8 (17%) developed neither. Early (day, 0–5) plasma sST2 levels were higher among patients with new or worsening EAs (median 115 ng/mL [interquartile range, 73.8–197]) versus those without (74.7 ng/mL [interquartile range, 44.8–102]; P =0.024). Plasma sST2 levels were similar between patients with or without new background deterioration. Repeated measures mixed-effects modeling that adjusted for admission risk factors showed that the association with new or worsening EAs remained independent for both plasma sST2 (β=0.41 [95% CI, 0.09–0.73]; P =0.01) and cerebrospinal fluid sST2 (β=0.97 [95% CI, 0.14–1.8]; P =0.021). IL-6 and CRP were not associated with new background deterioration or with new or worsening EAs. Conclusions— In patients admitted with subarachnoid hemorrhage, sST2 level was associated with new or worsening EAs but not new background deterioration. This association may identify a link between a specific innate immune response pathway and continuous electroencephalography abnormalities in the pathogenesis of secondary brain injury after subarachnoid hemorrhage.

BACKGROUND Patients with an in-breast tumor recurrence (IBTR) after breast-conserving therapy have a high risk of distant metastasis and disease-related mortality. Classifying clinical parameters that increase risk for recurrence after IBTR remains a challenge. AIM To describe primary and recurrent tumor characteristics in patients who experience an IBTR and understand the relationship between these characteristics and disease outcomes. METHODS Patients with stage 0-II breast cancer treated with lumpectomy and adjuvant radiation were identified from institutional databases of patients treated from 2003-2017 at our institution. Overall survival (OS), disease-free survival, and local recurrence-free survival (LRFS) were estimated using the Kaplan Meier method. We identified patients who experienced an isolated IBTR. Concordance of hormone receptor status and location of tumor from primary to recurrence was evaluated. The effect of clinical and treatment parameters on disease outcomes was also evaluated. RESULTS We identified 2164 patients who met the eligibility criteria. The median follow-up for all patients was 3.73 [interquartile range (IQR) 2.27-6.07] years. Five-year OS was 97.7% (95%CI: 96.8%-98.6%) with 28 deaths; 5-year LRFS was 98.0% (97.2-98.8) with 31 IBTRs. We identified 37 patients with isolated IBTR, 19 (51.4%) as ductal carcinoma in situ and 18 (48.6%) as invasive disease, of whom 83.3% had an in situ component. Median time from initial diagnosis to IBTR was 1.97 (IQR: 1.03-3.5) years. Radiotherapy information was available for 30 of 37 patients. Median whole-breast dose was 40.5 Gy and 23 patients received a boost to the tumor bed. Twenty-five of thirty-two (78.1%) patients had concordant hormone receptor status, HER-2 receptor status, and estrogen receptor (ER) (P = 0.006) and progesterone receptor (PR) (P = 0.001) status from primary to IBTR were significantly associated. There were no observed changes in HER-2 status from primary to IBTR. The concordance between quadrant of primary to IBTR was 10/19 [(62.2%), P = 0.008]. Tumor size greater than 1.5 cm (HR = 0.44, 95%CI: 0.22-0.90, P = 0.02) and use of endocrine therapy upfront (HR = 0.36, 95%CI: 0.18-0.73, P = 0.004) decreased the risk of IBTR. CONCLUSION Among patients with early stage breast cancer who had breast conserving surgery treated with adjuvant RT, ER/PR status and quadrant were highly concordant from primary to IBTR. Tumor size greater than 1.5 cm and use of adjuvant endocrine therapy were significantly associated with decreased risk of IBTR.

Backgrounds As the prevalence of dementia rises, caregiver burden also increases in South Korea, especially for informal family caregivers. This study aimed to analyze factors affecting caregiver burden by the severity of dementia based on data of patients in Seoul. Methods A total of 12,292 individuals aged ≥65 years enrolled in the Seoul Dementia Management Project from 2010 to 2016 in an online database were selected. Caregiver’s burden was assessed using the Korea version of Zarit Burden Interview. Multiple regression analyses were performed to determine factors associated with primary caregiver’s burden after stratifying the severity of dementia. Results Most patients showed moderate levels of cognitive impairment (49.4%), behavior problems (82.6%), and ADL dependency (73.6%). After stratifying the severity of dementia, caregivers caring for patients with mild symptoms of dementia were experienced with higher caregiver burden if patients were under a lower score of IADL. Significant factors for caregiver burden among caregivers supporting patients with moderate symptoms of dementia include caregivers’ residence with patients, subjective health status, and co-work with secondary caregivers. Lastly, caregivers for patients with severe dementia symptoms experienced a higher caregiver burden from limited cognitive function, problematic behavior, and caregivers’ negative health status. Conclusion In terms of sample size, this study had far more patients than any other domestic or international study. It was meaningful in that it analyzed characteristics of patients with dementia and caregivers affecting the burden of caregivers in Korea. Intensive social supports with multiple coping strategies focusing on different levels of patients’ clinical symptoms and caregivers’ needs should be planned to relieve the caregiver burden.

Background: Asian Canadians and Asian Americans face COVID-19–related discrimination. The objective of this qualitative study was to explore the experiences of Asian health care workers dealing with discrimination, with a focus on racial micro-agressions, in Canada and the United States during the COVID-19 pandemic. Methods: We adopted a qualitative descriptive approach. We used convenience and snowball sampling strategies to recruit participants. We conducted individual, in-depth semistructured interviews with Asian health care workers in Canada and the US via videoconferencing between May and September 2020. Eligible participants had to self-identify as Asian and be currently employed as a health care worker with at least 1 year of full-time employment. We used an inductive thematic approach to analyze the data. Results: Thirty participants were recruited. Fifteen (50%) were Canadians and 15 (50%) were Americans; there were 18 women (60%), 11 men (37%) and 1 nonbinary person. Most of the participants were aged 25–29 years (n = 16, 53%). More than half were nurses (n = 16, 53%); the other participants were attending physicians (n = 5), physiotherapists (n = 3), resident physicians (n = 2), a midwife, a paramedic, a pharmacist and a physician assistant. Two themes emerged from the data: a surge of racial microaggressions related to COVID-19 and a lack of institutional and public acknowledgement. Participants noted that they have experienced an increase in racial microaggressions during the COVID-19 pandemic. They have also experienced threats of violence and actual violence. The largely silent organizational response to the challenges being faced by people of Asian descent and the use of disparaging terms such as “China virus” in the early stages of the pandemic were a substantial source of frustration. Interpretation: Asian health care workers have experienced challenges in dealing with racial microaggressions related to COVID-19 in the US and Canada. More research should be done on the experiences of Asian Americans and Asian Canadians, both during and after the pandemic, and supportive measures should be put in place to protect Asian health care workers.

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 ( p = 0.006), an AUC[mRS>2] of 0.71 versus 0.68 ( p = 0.004), and an AUC[mRS>3] of 0.71 versus 0.69 ( p = 0.029). In multiple regression analysis adjusted for known outcome predictors, the maximum coronal diameter was independently associated with three-month mRS (p 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.

Background: Currently there remains controversy in the surgical management of rhegmatogenous retinal detachment (RRD) due to giant retinal tears (GRTs), a potentially blinding condition. To clarify which surgical technique is better depending on the origin and magnitude of the giant tear this study aimed to analyze the anatomical and functional outcomes. To analyze trans- and postoperative surgical complications, we used long-term final postoperative structural, optical coherence tomography (OCT) and correlated the results with the final postoperative best-corrected visual acuity (BCVA) in three different groups of eyes.Methods: Seventy-six consecutive eyes of 66 patients from three participant institutions were recruited and classified according to the degree of GRT-associated RRD extension as follows: group 1, 42 eyes with GRT-associated RRD extension < 180°; group 2, 23 eyes with GRT-associated RRD extension = 180°–270°; and group 3, 11 eyes with GRT-associated RRD extension > 270°. Structural and functional outcomes were compared across groups.Results: Of the 76 eyes analyzed, 63 were phakic, and 13 were pseudophakic. The mean age of the patients was 43.0 ±13.0 years (range, 19–76 years); 36 females, and 40 males. The mean preoperative time for GRT surgery was 1.8 weeks, the mean preoperative and postoperative BCVA was 1.87 logMAR and 0.35 logMAR, respectively (pConclusions: Multiple structural alterations in spectral-domain OCT biomarkers were observed. Eyes that developed secondary epiretinal membrane (ERM) proliferation showed significantly improved BCVA after proliferation, and the internal limiting membrane was removed. This study presents the severe consequences of macular structure and function. The structural findings correlated with the BCVA allow us to conclude severe consequences of the macular structure and that, despite a fully reattached retina without ERM proliferation, GRTs-associated RRD has a guarded functional prognosis.

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 p-value p-value p-value = 0.02) or financial aid (β: 0.64, p-value 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.

ObjectiveProgestin therapy is the recommended fertility-sparing management of atypical endometrial hyperplasia or early-stage endometrial cancer in reproductive-aged women. Our objective was to evaluate disease relapse after progestin and metformin versus progestin therapy alone in patients with endometrial hyperplasia or cancer. Our secondary outcomes were disease remission, clinical pregnancy and live birth rate.MethodsA systematic review of the literature was conducted (MEDLINE, Web of Science, Cochrane Library, CINAHL, LILACS, clinicaltrials.gov) from inception to April 2021. Studies of reproductive-aged women with atypical endometrial hyperplasia or early endometrial cancer who received progestin and metformin or progestin alone for fertility-sparing management, were included in the review. Early endometrial cancer was defined as grade 1, stage 1 disease. Exclusion criteria included women with higher grade endometrial cancer and when conservative management was not for fertility-sparing purposes. Data are presented as odds ratios (ORs) and 95% confidence intervals (CIs) with fixed or random effects meta-analysis. Quality scoring was based on the Newcastle-Ottawa and Jadad scales.ResultsIn total, 271 reports were identified and six studies met the inclusion criteria. These studies included 621 women; 241 (38.8%) patients received combined therapy and 380 (61.2%) received progestin therapy alone. Relapse rates were lower for progestin and metformin than for progestin therapy alone (pooled OR 0.46, 95% CI 0.24 to 0.91, p=0.03). The remission rates were not different (pooled OR 1.35, 95% CI 0.91 to 2.00, p=0.14). Women who received progestin and metformin achieved pregnancy and live birth rates similar to those who received progestin therapy only (pooled OR 1.01, 95% CI 0.44 to 2.35, p=0.98; pooled OR 0.46, 95% CI 0.21 to 1.03, p=0.06).ConclusionFor reproductive-aged women with atypical endometrial hyperplasia or early endometrial cancer, progestin and metformin therapy compared with progestin therapy alone is associated with lower relapse rates, and similar remission, clinical pregnancy and live birth rates.PROSPERO registration numberCRD42020179069.disease remission

(1) To describe electronic communication between global surgeons and trainees in a low-middle income country (LMIC) and to gauge appeal of the WhatsApp platform (2) To introduce a novel intensive ear reconstruction teaching module for surgical capacity building using simulation in a LMIC.Prospective cohort study.University-based medical center in Haiti.Eleven otolaryngology trainees and faculty in Haiti.Three months prior to on-site arrival, a WhatsApp Messenger group was created for information-sharing and distribution of teaching materials. A surgical curriculum was created to incorporate didactics, cartilage framework simulation, and live surgery. During the intensive on-site week, WhatsApp was used to distribute materials and to recap learning points from each case, with pre- and postoperative surgical photographs circulated. Postmodule written, oral, and practical testing was conducted on the final day, and a postmodule survey was administered a month later. Post-tests scores were significantly improved from pretests scores. Initial scores on the written, oral, and practical tests averaged 24.6%. Postmodule scores averaged 86.9% (p0.001). Participants rated the use of WhatsApp to be highly important to their learning and requested further use of mobile health technology.WhatsApp Messenger technology complemented a reconstructive surgery education module in a LMIC. WhatsApp provides opportunities for premodule patient screening, real-time discussion, and postmodule review. Its usage was well-received by Haitian otolaryngology trainees and faculty. Our results suggest that the combination of didactic teaching, simulated surgery, and live surgery resulted in successful transfer of both skills and knowledge.

Background: Despite general increases in statin use in the United States, statin therapy may be underutilized in diabetic patients and vulnerable populations. Objective: To determine the impact of a collaborative pharmacist initiative on statin prescribing for diabetic patients in an internal medicine residency clinic. The primary outcome was the change in prevalence of patients on statin therapy before and after intervention implementation. Secondary outcomes included recommendation acceptance rates and reported adverse effects. Methods: This was a single-center, quasi-experimental pre–post intervention study. The study site was a hospital-based primary care residency clinic serving patients regardless of financial or insurance status. Diabetic patients 40 to 75 years old who were not on a statin and had an upcoming primary care physician appointment were included. Over 3 months, a clinical pharmacist and pharmacy resident evaluated clinical appropriateness and cost of statin therapy, provided recommendations to physicians, facilitated statin prescribing, and provided patient education. Results: Of 454 patients, 343 were on statin therapy (75.6%) prior to the initiative. The mean age was 58 years, 59.7% were female, 76.4% were black, and 90% had hypertension. After implementation, 375 (82.6%) patients were on statins ( P < .0001). Recommendations were well received (90.2% accepted) and no significant adverse effects were reported. Conclusion: Pharmacist implementation of a collaborative, patient-centered initiative increased statin prescribing in diabetic patients, most of which were black and had hypertension, in an internal medicine resident clinic.

Flaccid facial paralysis results in disfiguring facial changes. The treatment of flaccid facial paralysis is complex and treatment approaches should be determined based on duration and the causes of paralysis, status and accessibility of the affected facial nerve, medical comorbidities, and patient-specific goals. Although primary nerve repair is the preferred treatment strategy when possible, nerve substitution procedures are the mainstay of treatment for patients with flaccid facial paralysis of less than 2 years duration.

IMPORTANCE: Traumatic brain injury (TBI) leads to 2.9 million visits to US emergency departments annually and frequently involves a disorder of consciousness (DOC). Early treatment, including withdrawal of life-sustaining therapies and rehabilitation, is often predicated on the assumed worse outcome of disrupted consciousness. OBJECTIVE: To quantify the loss of consciousness, factors associated with recovery, and return to functional independence in a 31-year sample of patients with moderate or severe brain trauma. DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed patients with TBI who were enrolled in the Traumatic Brain Injury Model Systems National Database, a prospective, multiyear, longitudinal database. Patients were survivors of moderate or severe TBI who were discharged from acute hospitalization and admitted to inpatient rehabilitation from January 4, 1989, to June 19, 2019, at 1 of 23 inpatient rehabilitation centers that participated in the Traumatic Brain Injury Model Systems program. Follow-up for the study was through completion of inpatient rehabilitation. EXPOSURES: Traumatic brain injury. MAIN OUTCOMES AND MEASURES: Outcome measures were Glasgow Coma Scale in the emergency department, Disability Rating Scale, posttraumatic amnesia, and Functional Independence Measure. Patient-related data included demographic characteristics, injury cause, and brain computed tomography findings. RESULTS: The 17 470 patients with TBI analyzed in this study had a median (interquartile range [IQR]) age at injury of 39 (25-56) years and included 12 854 male individuals (74%). Of these patients, 7547 (57%) experienced initial loss of consciousness, which persisted to rehabilitation in 2058 patients (12%). Those with persisting DOC were younger; had more high-velocity injuries; had intracranial mass effect, intraventricular hemorrhage, and subcortical contusion; and had longer acute care than patients without DOC. Eighty-two percent (n = 1674) of comatose patients recovered consciousness during inpatient rehabilitation. In a multivariable analysis, the factors associated with consciousness recovery were absence of intraventricular hemorrhage (adjusted odds ratio [OR], 0.678; 95% CI, 0.532-0.863; P = .002) and intracranial mass effect (adjusted OR, 0.759; 95% CI, 0.595-0.968; P = .03). Functional improvement (change in total functional independence score from admission to discharge) was +43 for patients with DOC and +37 for those without DOC (P = .002), and 803 of 2013 patients with DOC (40%) became partially or fully independent. Younger age, male sex, and absence of intraventricular hemorrhage, intracranial mass effect, and subcortical contusion were associated with better functional outcome. Findings were consistent across the 3 decades of the database. CONCLUSIONS AND RELEVANCE: This study found that DOC occurred initially in most patients with TBI and persisted in some patients after rehabilitation, but most patients with persisting DOC recovered consciousness during rehabilitation. This recovery trajectory may inform acute and rehabilitation treatment decisions and suggests caution is warranted in consideration of withdrawing or withholding care in patients with TBI and DOC.

Introduction: Delayed cerebral ischemia (DCI) is the leading complication of subarachnoid hemorrhage (SAH). Because DCI was traditionally thought to be caused by large vessel vasospasm, transcranial Doppler ultrasounds (TCDs) have been the standard of care. Continuous EEG has emerged as a promising complementary monitoring modality and predicts increased DCI risk. Clinical variables have also been used in DCI prediction. We hypothesize integrating these diagnostic modalities improves DCI prediction. Methods: We assessed 107 patients with moderate-severe SAH (2011-2015) who had both TCD and EEG monitoring during hospitalization. Clinical demographics, including Hunt-Hess and aneurysm treatment (clipping/coiling), were collected via retrospective chart review. Middle cerebral artery (MCA) peak systolic velocities (PSV) and the presence or absence of epileptiform abnormalities (EA), defined as seizures, epileptiform discharges, and rhythmic/periodic activity, were recorded daily. Logistic regressions were used to identify EEG, TCD, and clinical variables associated with DCI. Group-Based Trajectory Modeling (GBTM) was used to account for changes over time by identifying distinct group trajectories of MCA and EA associated with DCI risk. Results: Independent predictors of DCI in logistic regressions are: presence of high MCA velocity (PSV≥200cm/s) and presence of EA on or before day 3. There are 2 univariate GBTM trajectories of EA (%DCI in group 1=32.1, group 2=70.4) significantly associated with DCI, but MCA velocity trajectories are not significant. Logistic regression and GBTM models using both TCD and EEG monitoring improve upon models using either modality alone. Hunt-Hess score at admission and aneurysm treatment as covariates further improved model performance. The best models used both TCD and EEG monitoring modalities and clinical variables as predictors (logistic regression: Se=90%, Sp=70%; GBTM: Se=89%, Sp=67%). Conclusions: EEG and TCD biomarkers combined provide the best prediction of DCI, compared to either alone. Models that considered the timing of EA and high MCA velocities plus clinical variables improved model performance.

Background and Aims: Advances in low-field MRI have enabled image acquisition at the point-of-care (POC). We aim to characterize ischemic lesions in low-field, POC MRI and assess its relationship with stroke severity in ischemic stroke patients. Methods: We performed POC MRI exams on ischemic stroke patients. T2-weighted (T2W), fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging (DWI) exams were acquired with a 64mT, portable bedside MRI system. Three raters computed signal intensity ratios (SIR) for each sequence. For every slice showing an infarct, an SIR was generated by dividing the mean signal intensity of the lesion by the mean signal intensity of the contralateral hemisphere. Infarct volumes were obtained by multiplying the lesion area of each slice by the slice thickness (5mm) and summing the cross-sectional areas. Volumes were correlated with National Institutes of Health Stroke Scale (NIHSS) scores at the time of scan. Results: We studied 18 ischemic stroke patients (50% women; ages 30-95 years). Two patients were studied at two and three serial timepoints, respectively. POC exams were obtained 2.7 ± 2.2 days after symptom onset. A total of 18 T2W, 17 FLAIR, and 18 DWI exams were obtained. Three exams (1 T2W; 1 FLAIR; 1 DWI) were excluded due to motion degradation. High field MRI exams (19 ± 16 hours from POC exams) demonstrated ischemic infarcts in 15 of the 18 patients. All POC T2W and FLAIR exams revealed infarcts in these patients, and 14 of the 17 DWI exams showed infarcts. Ischemic infarcts were seen as hyperintense lesions (SIR: T2W = 1.19 ± 0.10, FLAIR = 1.15 ± 0.08, DWI = 1.36 ± 0.17). Infarct volume significantly correlated with NIHSS scores (T2W: r = 0.71, p < 0.01; FLAIR: r = 0.65, p < 0.05; DWI: r = 0.65, p < 0.05). Conclusions: These preliminary data suggest that low-field, POC MRI may be useful in the clinical evaluation of ischemic stroke. Further work in larger cohorts is needed to elucidate the appearance of infarction on low-field imaging.

Objectives: Seizures and seizure-like electroencephalography (EEG) patterns, collectively referred to as “ictal interictal injury continuum” (IIIC) patterns, are commonly encountered in critically ill patients. Automated detection is important for patient care and to enable research. However, training accurate detectors requires a large labeled dataset. Active Learning (AL) may help select informative examples to label, but the optimal AL approach remains unclear. Methods: We assembled >200,000 h of EEG from 1,454 hospitalized patients. From these, we collected 9,808 labeled and 120,000 unlabeled 10-second EEG segments. Labels included 6 IIIC patterns. In each AL iteration, a Dense-Net Convolutional Neural Network (CNN) learned vector representations for EEG segments using available labels, which were used to create a 2D embedding map. Nearest-neighbor label spreading within the embedding map was used to create additional pseudo-labeled data. A second Dense-Net was trained using real- and pseudo-labels. We evaluated several strategies for selecting candidate points for experts to label next. Finally, we compared two methods for class balancing within queries: standard balanced-based querying (SBBQ), and high confidence spread-based balanced querying (HCSBBQ). Results: Our results show: 1) Label spreading increased convergence speed for AL. 2) All query criteria produced similar results to random sampling. 3) HCSBBQ query balancing performed best. Using label spreading and HCSBBQ query balancing, we were able to train models approaching expert-level performance across all pattern categories after obtaining ∼7000 expert labels. Conclusion: Our results provide guidance regarding the use of AL to efficiently label large EEG datasets in critically ill patients., SCOPUS: ar.j, info:eu-repo/semantics/published

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.

Indications and procedural techniques for successful transvenous embolization of cerebral dural arteriovenous fistulas (dAVFs) are reviewed. A brief historic context for transvenous embolization is presented. We discuss important anatomical considerations and present illustrative cases for ideal scenarios and more challenging transvenous approaches.

Background Patients with aneurysmal subarachnoid hemorrhage (aSAH) with electroencephalographic epileptiform activity (seizures, periodic and rhythmic patterns, and sporadic discharges) are frequently treated with antiseizure medications (ASMs). However, the safety and effectiveness of ASM treatment for epileptiform activity has not been established. We used observational data to investigate the effectiveness of ASM treatment in patients with aSAH undergoing continuous electroencephalography (cEEG) to develop a causal hypothesis for testing in prospective trials. Methods This was a retrospective single-center cohort study of patients with aSAH admitted between 2011 and 2016. Patients underwent ≥ 24 h of cEEG within 4 days of admission. All patients received primary ASM prophylaxis until aneurysm treatment (typically within 24 h of admission). Treatment exposure was defined as reinitiation of ASMs after aneurysm treatment and cEEG initiation. We excluded patients with non-cEEG indications for ASMs (e.g., epilepsy, acute symptomatic seizures). Outcomes measures were 90-day mortality and good functional outcome (modified Rankin Scale scores 0-3). Propensity scores were used to adjust for baseline covariates and disease severity. Results Ninety-four patients were eligible (40 continued ASM treatment; 54 received prophylaxis only). ASM continuation was not significantly associated with higher 90-day mortality (propensity-adjusted hazard ratio [HR] = 2.01 [95% confidence interval (CI) 0.57-7.02]). ASM continuation was associated with lower likelihood for 90-day good functional outcome (propensity-adjusted HR = 0.39 [95% CI 0.18-0.81]). In a secondary analysis, low-intensity treatment (low-dose single ASM) was not significantly associated with mortality (propensity-adjusted HR = 0.60 [95% CI 0.10-3.59]), although it was associated with a lower likelihood of good outcome (propensity-adjusted HR = 0.37 [95% CI 0.15-0.91]), compared with prophylaxis. High-intensity treatment (high-dose single ASM, multiple ASMs, or anesthetics) was associated with higher mortality (propensity-adjusted HR = 6.80 [95% CI 1.67-27.65]) and lower likelihood for good outcomes (propensity-adjusted HR = 0.30 [95% CI 0.10-0.94]) compared with prophylaxis only. Conclusions Our findings suggest the testable hypothesis that continuing ASMs in patients with aSAH with cEEG abnormalities does not improve functional outcomes. This hypothesis should be tested in prospective randomized studies.

Introduction: Neuroinflammation has been linked to poor neurologic and functional outcomes in many cerebrovascular disorders. Immune checkpoints are upregulated in the setting of traumatic brain in...

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.

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/dL reduction (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 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.

Brain metastasis is common in patients with breast cancer, and those with triple negative status have an even higher risk. Stereotactic radiosurgery (SRS) is preferred to whole brain radiation therapy (WBRT) in most patients. However, triple negative status is currently not considered when determining optimal radiation therapy. Given the aggressive nature of triple negative breast cancer, we evaluated a role for WBRT for all patients in this cohort. We conducted a single-institution retrospective cohort study to determine whether triple negative patients with brain metastases have a higher burden of intracranial disease and whether type of initial radiation therapy affects overall survival for this cohort of patients. 85 patients met the inclusion criteria for this study. 25% of patients had triple negative breast cancer, of which 91% received SRS and 53% of patients received WBRT. The average number of new brain metastases from time of initial brain imaging to radiation therapy was 0.67 (St.Dev:1.1) in the non-triple negative status patients and 2.6 (St. Dev:3.7) in the triple negative status patients (p=0.001). Using a cox proportional hazards model, it was found that whole brain radiotherapy does not significantly affect overall survival in patients with triple negative breast cancer (p = 0.96). Our findings highlight the highly aggressive intracranial nature of triple negative breast cancer. Indeed, the rate of increase in brain metastases is significantly higher for triple negative patients compared to non-triple negative patients. As a result, we evaluated whether triple negative patients would benefit from whole brain radiation regardless of findings on initial brain imaging. Despite 53% of patients receiving WBRT, our investigation found that there is no additional benefit to WBRT in triple negative breast cancer patients. These results suggest a need to re-evaluate the role of WBRT in the management of triple negative breast cancer.

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

Purpose The steady development of biotechnology-derived therapeutic biologics over the last few decades has generated drugs that are now standard medical treatments for a range of indications. While the development of protein products has surged in recent years, the formulation and delivery of these complex molecules have relied on drug-specific studies and, in some instances, data from non-proteinaceous drug products. The commonalities, trends, and gaps in excipient technologies used to support the development of therapeutic proteins largely remain unexplored due to the drug-specific nature of many formulations. Methods Using a comprehensive and relational database approach, we aimed to provide a scientific survey of all approved or licensed biotechnology-derived drug products with the goal of providing evidence-based information on common attributes and trending features in protein product excipients. We examined 665 formulations, and 395 unique formulations based on having unique excipients within them, that supported 211 therapeutic proteins as of June 2020. Results We report the prevalence of each excipient class and excipient chemical used in eight different drug types including monoclonal antibodies, antibody conjugates, cytokines and growth factors, enzymes, polypeptide hormones, pulmonary surfactants, recombinant fusion proteins, and toxins. We also report the prevalence by excipient type among all therapeutic proteins, in the context of each drug’s recommended pH range, concentration ranges for excipients, and route of administration. Conclusions The results of our analyses indicate certain excipients common to monoclonal antibodies, cytokines, and polypeptide hormones. We also report on excipients unique to protein drug products, such as amino acids, solubilizers, and lyoprotectants. Overall, our report summarizes the current landscape of excipients used in marketed biotechnology-derived therapeutic biologic products.

Importance: Masseteric-to-facial nerve transfer has gained popularity as a technique that provides dynamic voluntary function in unilateral facial paralysis. Despite the multiple studies that have ...

PURPOSE OF REVIEW: Acute brain injury (ABI) is a broad category of pathologies, including traumatic brain injury, and is commonly complicated by seizures. Electroencephalogram (EEG) studies are used to detect seizures or other epileptiform patterns. This review seeks to clarify EEG findings relevant to ABI, explore practical barriers limiting EEG implementation, discuss strategies to leverage EEG monitoring in various clinical settings, and suggest an approach to utilize EEG for triage. RECENT FINDINGS: Current literature suggests there is an increased morbidity and mortality risk associated with seizures or patterns on the ictal-interictal continuum (IIC) due to ABI. Further, increased use of EEG is associated with better clinical outcomes. However, there are many logistical barriers to successful EEG implementation that prohibit its ubiquitous use. SUMMARY: Solutions to these limitations include the use of rapid EEG systems, non-expert EEG analysis, machine learning algorithms, and the incorporation of EEG data into prognostic models.

Objective: Worsening epileptiform abnormalities (EAs) and deteriorating background activity are common continuous electroencephalography (cEEG) patterns that predict subsequent clinical deterioration following subarachnoid hemorrhage (SAH). While worsening EAs and background deterioration both imply cortical dysfunction, we sought to clarify if these patterns have a different association with clinical outcomes. Methods: We enrolled patients with SAH undergoing > 3 days of cEEG monitoring enrolled in a prospective outcome study with a modified Rankin Scale (mRS) assessment at 3 months. Worsening EAs included new or increasing burden of sporadic epileptiform discharges, lateralized rhythmic delta activity (LRDA), lateralized periodic discharges (LPD), or generalized periodic discharges (GPD). Background deterioration was defined as decreasing Alpha Delta Ratio (ADR), Relative Alpha Variability (RAV) or worsening focal slowing. We evaluated the association between these cEEG patterns and 3-month mRS >3 and examined whether the influence on outcome was independent of delayed cerebral ischemia (DCI). Results: Of 59 patients meeting inclusion criteria (3-month mRS median 3 [IQR 1-5]), worsening EAs developed in 23 (39%) and new background deterioration in 24 (41%), whereas 24 patients (41%) developed neither finding and 12 (20%) developed both. Patients with worsening EAs were more likely to have a poor 3-month mRS compared to those without worsening EAs (OR 6.44; 95%CI 1.99-20.9; p=0.001). Developing new background deterioration was not significantly associated with poor 3-month outcome (OR 1.56, 95%CI 0.53-4.59; p=0.42). There was no additive effect on poor outcome of developing both findings. In a multivariate logistic regression, the effect of worsening EAs on 3-month mRS was independent of DCI. Interpretation: While both worsening EAs and new background deterioration have previously been associated with DCI, only worsening EAs influences poor long-term outcome. Further investigation may clarify if distinct mechanisms underlie these differences.

Many types of neurologic injury are known to affect the cardiovascular system. Both rhythm and pump function can be dramatically affected. In this chapter, we review the cardiovascular changes that can be seen after neurologic injury and the specific neurologic diseases most commonly associated with those changes. This chapter covers hypertension, cardiomyopathy, shock, arrhythmias, and myocardial ischemia. These neurocardiogenic changes are important to diagnose, understand, and manage in order to simultaneously optimize neurologic recovery and cardiovascular function. Recognition of these neurocardiovascular connections can help neurointensivists and cardiologists best understand the underlying driving forces behind hemodynamic instabilities that can be seen in patients after acute neurologic injury.