BACKGROUND:Patients with oncologic spine disease face a high systemic illness burden and often require surgical intervention to alleviate pain and maintain spine stability. Wound healing complications are the most common reason for reoperation in this population and are known to impact quality of life and initiation of adjuvant therapy. Prophylactic muscle flap (MF) closure is known to reduce wound healing complications in high-risk patients; however, the efficacy in oncologic spine patients is not well established.METHODS:A collaboration at our institution presented an opportunity to study the outcomes of prophylactic MF closure. The authors performed a retrospective cohort study of patients who underwent MF closure versus a cohort who underwent non-MF closure in the preceding time. Demographic and baseline health data were collected, as were postoperative wound complication data.RESULTS:A total of 166 patients were enrolled, including 83 patients in the MF cohort and 83 control patients. Patients in the MF group were more likely to smoke ( P = 0.005) and had a higher incidence of prior spine irradiation ( P = 0.002). Postoperatively, five patients (6%) in the MF group developed wound complications, compared with 14 patients (17%) in the control group ( P = 0.028). The most common overall complication was wound dehiscence requiring conservative therapy, which occurred in six control patients (7%) and one MF patient (1%) ( P = 0.053).CONCLUSIONS:Prophylactic MF closure during oncologic spine surgery significantly reduces the wound complication rate. Future studies should examine the precise patient population that stands to benefit most from this intervention.CLINICAL QUESTION/LEVEL OF EVIDENCE:Therapeutic, III.

-OBJECTIVE: Virtual mentorship and research programs are becoming increasingly popular to facilitate education and career development for students and residents. We review virtual research initiatives for early trainees in neurosurgery and describe our effort to expand access to resources and shared objective mentorship (SOM) via the novel Neurosurgery Education and Research Virtual Group (NERVE).-METHODS: A systematic review of neurosurgical programming delivered via a virtual platform was conducted using PubMed, Embase, and Scopus data-bases. Identified articles were screened. Those meeting prespecified inclusion criteria were reviewed in full and examined for relevant data. Data analysis was performed using Microsoft Excel, and means and standard deviations were calculated. Descriptive analysis of NERVE characteristics was also performed.-RESULTS: Of the 2438 identified articles, 10 were included. The most common (70%) implementation style was a webinar-based lecture series. The least common (10%) was a longitudinal curricular interest group. Of the total NERVE cohort, 90% were first generation medical students and 82% attended in-stitutions without home programs. Survey results indicated 73.8% had contrib-uted to at least 2 research projects throughout the year.-CONCLUSIONS: There is a scarcity of virtual neurosurgical resources which facilitate SOM opportunities for trainees. In our systematic review, NERVE is the only multi-institutional virtual initiative aimed at increasing access to neuro-surgical education and research opportunities for the purpose of SOM among early trainees from disadvantaged backgrounds. This highlights the group's -iche and potential impact on increasing diversity in neurosurgery, improving trainees' career development, and facilitating future resident research productivity.

With the incidence of central and peripheral nervous system disorders on the rise, neurosurgical procedures paired with the careful administration of select medications have become necessary to optimize patient outcomes. Despite efforts to decrease the over-prescription of common addictive drugs, such as opioids, prescription costs continue to rise. This study analyzed temporal trends in medication use and cost for spinal fusion and brain tumor resection procedures. The Medicare Part B Database was queried from 2016 to 2020 for data regarding spinal fusion and brain tumor resection procedures, while the Part D Database was used to extract data for two commonly prescribed medications for each procedure. Pearson's correlation coefficient and linear regression were completed for the analyzed variables. The results showed a significant negative correlation between the number of spinal procedure beneficiaries and the cost of methocarbamol, as well as between the annual percent change in spinal beneficiaries and the annual percent change in oxycodone cost. Linear regression revealed that oxycodone cost was the only parameter with a statistically significant model. Moving forward, it is imperative to combat rising drug costs, regardless of trends seen in their usage. Further studies should focus on the utilization of primary data in a multi-center study.

Background Few studies have assessed the impact of race on short-term patient outcomes in the brain metastasis population. The goal of this study is to evaluate the association of race with inpatient clinical presentation, treatment, in-hospital complications, and in-hospital mortality rates for patients with brain metastases (BM). Method Using data collected from the National Inpatient Sample between 2004 and 2014, we retrospectively identified adult patients with a primary diagnosis of BM. Outcomes included nonroutine discharge, prolonged length of stay (pLOS), in-hospital complications, and mortality. Results Minority (Black, Hispanic/other) patients were less likely to receive surgical intervention compared to White patients (odds ratio [OR] 0.70; 95% confidence interval [CI] 0.66-0.74, p < 0.001; OR 0.88; 95% CI 0.84-0.93, p < 0.001). Black patients were more likely to develop an in-hospital complication than White patients (OR 1.35, 95% CI 1.28-1.41, p < 0.001). Additionally, minority patients were more likely to experience pLOS than White patients (OR 1.48; 95% CI 1.41-1.57, p < 0.001; OR 1.34; 95% CI 1.27-1.42, p < 0.001). Black patients were more likely to experience a nonroutine discharge (OR 1.25; 95% CI 1.19-1.31, p < 0.001) and higher in-hospital mortality than White (OR 1.13; 95% CI 1.03-1.23, p = 0.008). Conclusion Our analysis demonstrated that race is associated with disparate short-term outcomes in patients with BM. More efforts are needed to address these disparities, provide equitable care, and allow for similar outcomes regardless of care.

Introduction The optimal treatment regimen for herpes simplex-1 (HSV-1) encephalitis is ill-defined. Current guidelines recommend the initiation of acyclovir in all suspected cases of encephalitis; however, there is limited research regarding the details of acyclovir treatment or the adjuvant use of corticosteroids. Specifically, there is a paucity of evidence-based guidelines detailing the optimal management of HSV-1 encephalitis in immunocompetent patients. In this study, we conducted a review of cases of immunocompetent patients with HSV-1 encephalitis to compare patterns in treatment and outcomes. Methods A review of the literature was performed using PubMed using the terms herpes encephalitis, HSV, herpes zoster, and immunocompetent to identify cases of HSV-1 encephalitis in immunocompetent patients. The results were screened for cases describing the treatment regimen of HSV-1 encephalitis-positive, immunocompetent patients. Results Six cases were identified. All six patients were treated with acyclovir with one patient receiving adjuvant corticosteroid therapy. Additionally, three patients were found to have acyclovir resistance and were transitioned to foscarnet. Eventually, one patient expired, two patients recovered with chronic morbidities of varying severity, and three patients made a full recovery. Discussion Inconsistencies in the patient's disease course, therapeutic regimen, and comorbidities could all play a role in the varying case outcomes. While the optimal timing and composition of therapies in HSV-1 encephalitis in immunocompetent patients are still unclear, it seems the timely administration of antiviral treatment remains essential. Further research is needed to optimize HSV-1 encephalitis therapeutic regimens and improve patient outcomes.

Acute alcohol intoxication is a common presentation to emergency departments. The intoxication of young pediatric patients is extremely rare. We present a case of a two-year-old female who presented to the emergency department with altered mentation, incontinence, and hypoglycemia. Over the next two days, the patient was treated with fluid replacement, and her hypoglycemia was managed. She was then discharged with no complications. While infant ethanol intoxication has a relatively low mortality rate, it can still be potentially fatal due to complications. Few studies have examined the morbidity associated with these presentations. This case demonstrates the importance of prompt identification and management to avoid a catastrophic outcome. Further research on the enzyme kinetics and long-term effects of early ethanol exposure resulting in hypoglycemia and ketosis is warranted.

Student-run clinics (SRCs) are becoming increasingly popular at medical schools in the United States.These clinics have provided a variety of benefits, including serving disadvantaged populations and providing early clinical exposure for students.There has been no consensus on the impact of SRCs on medical education, specialty selection, and patient care.This review provides a thorough overview of student and patient outcomes as a function of medical students volunteering at SRCs.We queried PubMed for original literature published in English between the years 2000 and 2020.Inclusion criteria included primary research articles evaluating the impact of medical student participation in SRCs on education, specialty selection, and patient care.All articles included in the final review were agreed upon by three reviewers, and the pertinent data were extracted.Of 10,200 initial search results, seven papers were included in this review.These included two studies evaluating medical education, five studies evaluating residency selection, and three studies analyzing patient care.Three studies were included in multiple evaluations.The relationship between volunteering at SRCs and academic performance is unclear.Clinic volunteers had increased retention of empathy compared to non-volunteers.Additionally, clinic volunteers provided satisfactory care as determined by patient-reported outcomes, and were not more likely to pursue primary care specialties.As SRCs are increasing in number, research into the impact on medical students and patients is necessary to understand how these clinics may affect the field of health care.It is important to further evaluate how medical student involvement in SRCs can further improve patient care and outcomes.

Background: It is well established that insurance status is a mediator of disease management, treatment course, and clinical outcomes in cancer patients. Our study assessed differences in clinical presentation, treatment course, mortality rates, and in-hospital complications for patients admitted to the hospital with late-stage cancer - specifically, metastatic spine disease (MSD), by insurance status. Methods: The United States National Inpatient Sample (NIS) database (2012-2014) was queried to identify patients with visceral metastases, metastatic spinal cord compression (MSCC) or pathological fracture of the spine in the setting of cancer. Clinical presentation, type of intervention, mortality rates, and in-hospital complications were compared amongst patients by insurance coverage (Medicare, Medicaid, commercial or unknown). Multivariable logistical regression and age sensitivity analyses were performed. Results: A total of 48,560 MSD patients were identified. Patients with Medicaid coverage presented with significantly higher rates of MSCC (p < 0.001), paralysis (0.008), and visceral metastases (p < 0.001). Patients with commercial insurance were more likely to receive surgical intervention (OR 1.43; p < 0.001). Patients with Medicaid < 65 had higher rates of prolonged length of stay (PLOS) (OR 1.26; 95% CI, 1.01-1.55; p = 0.040) while both Medicare and Medicaid patients < 65 were more likely to have non-routine discharges. In-hospital mortality rates were significantly higher for patients with Medicaid (OR 2.66; 95% CI 1.20-5.89; p = 0.016) and commercial insurance (OR 1.58; 95% CI 1.09-2.27;p = 0.013) older than 65. Conclusion: Given the differing severity in MSD presentation, mortality rates, and rates of PLOS by insurance status, our results identify disparities based on insurance coverage.

Introduction: As of the 2020 National Resident Matching Program (NRMP), nearly all applicants are evaluated together for graduate medical education (GME) candidacy.We set out to characterize US MD and DO Senior residency match performance in the single-accreditation GME era.Methods: A retrospective study was conducted in 2021 utilizing data collected from the 2018 and 2020 NRMP Charting Outcomes in the Match publications aggregated and subdivided into three groups based on competitiveness: low (LC), moderate (MC), and high (HC).Nonparametric analysis was performed using Chi square or Fisher exact tests if counts were less than five.Significance was determined at p < 0.05.Results: A total of 46,853 candidates were included, with 36,194 (77.3%)US MD and 10,659 (22.7%)DO Seniors.Match rates for US DO Seniors were lower than US MD Seniors across all competitiveness strata (p < 0.0001).Research item production, national licensing examination scores, and mean number of contiguous programs ranked were lower for matched US DO Seniors compared to matched US MD Seniors, with significant differences depending on competitiveness group.Conclusions: With recent changes to GME and its application process, understanding how various groups compare will be increasingly important.US DO Seniors have lower first-rank match rates for all specialty competitiveness levels.This may be due to lower research output or nuanced specialty selection.This study could aid GME stakeholders to more effectively allocate resources and better prepare residency candidates.

Cheng, Ce DO; Masoud, John Azat BS; McCray, Edwin Thomas BS; Sun, Chenyu MD, MSc; Momodu, Ifeanyi MD, MPH, FACPEditor(s): Vitito, LeAnne MS, RN, CGRN, APRN, Department Editor Author Information

Robotic navigation is a new and rapidly emerging niche within minimally invasive spine surgery. The robotic arms-race began in 2004 and has resulted in no less than four major robotic surgical adjuncts. Current Food and Drug Administration (FDA)-approved applications of robotic navigation are limited to pedicle screw instrumentation, but new indications and experimental applications are rapidly emerging. As with any new technology, robotic navigation must be vetted for clinical efficacy, efficiency, safety, and cost-effectiveness. Given the rapid advancements made on a yearly basis, it is important to make frequent and objective assessments of the available technology. Thus, the authors seek to provide the most up-to-date review of the history, currently available technology, learning curve, novel applications, and cost effectiveness of today's available robotic systems as it relates to spine surgery.

OBJECTIVE:In patients with metastatic spinal disease (MSD), interhospital transfer can potentially impact clinical outcomes as the possible benefits of transferring a patient to a higher level of care must be weighed against the negative effects associated with potential delays in treatment. While the association of clinical outcomes and transfer status has been examined in other specialties, the relationship between transfer status, complications, and risk of mortality in patients with MSD has yet to be explored. The purpose of this study was to examine the impact of transfer status on in-hospital mortality and clinical outcomes in patients diagnosed with MSD.METHODS:The National (Nationwide) Inpatient Sample (NIS) database was retrospectively queried for adult patients diagnosed with vertebral pathological fracture and/or spinal cord compression in the setting of metastatic disease between 2012 and 2014. Demographics, baseline characteristics (e.g., metastatic spinal cord compression [MSCC] and paralysis), comorbidities, type of intervention, and relevant patient outcomes were controlled in a multivariable logistic regression model to analyze the association of transfer status with patient outcomes.RESULTS:Within the 10,360 patients meeting the inclusion and exclusion criteria, higher rates of MSCC (50.2% vs 35.9%, p < 0.001) and paralysis (17.3% vs 8.4%, p < 0.001) were observed in patients transferred between hospitals compared to those directly admitted. In univariable analysis, a higher percentage of transferred patients underwent surgical intervention (p < 0.001) when compared with directly admitted patients. After controlling for significant covariates and surgical intervention, transferred patients were more likely to develop in-hospital complications (OR 1.34, 95% CI 1.18-1.52, p < 0.001), experience prolonged length of stay (OR 1.33, 95% CI 1.16-1.52, p < 0.001), and have a discharge disposition other than home (OR 1.70, 95% CI 1.46-1.98, p < 0.001), with no significant difference in inpatient mortality rates.CONCLUSIONS:Patients with MSD who were transferred between hospitals demonstrated more severe clinical presentations and higher rates of inpatient complications compared to directly admitted patients, despite demonstrating no difference in in-hospital mortality rates.

Intracranial spread of a systemic malignancy is common in advanced staged cancers; however, metastasis specifically to the pineal gland is a relatively rare occurrence. A number of primary lesions have been reported to metastasize to the pineal gland, the most common of which is lung. However, metastasis of a bronchial neuroendocrine tumor to the pineal gland is a seldom-reported entity. Here, we present a 53-year-old female who presented with worsening headaches and drowsiness. MRI brain revealed a heterogeneously enhancing partially cystic mass in the pineal region. The patient had an extensive oncologic history consisting of remote stage IIA invasive breast ductal carcinoma as well as a more recently diagnosed atypical bronchopulmonary neuroendocrine tumor with lymph node metastases. She underwent microsurgical volumetric resection of the large pineal mass and a gross total removal of the tumor was achieved. Histopathology confirmed a metastatic tumor of neuroendocrine origin and the immunohistochemical profile was identical to the primary bronchopulmonary carcinoid tumor. Eight weeks after surgery, she underwent stereotactic radiosurgical treatment to the resection cavity. At 1-year follow-up, the patient remains clinically stable without any new focal neurological deficits and without any evidence of residual or recurrent disease on postoperative MRI. Metastatic neuroendocrine tumors should be considered in the differential diagnosis of pineal region tumors and aggressive surgical resection should be considered in selected patients. Gross total tumor resection may afford excellent local disease control. We discuss the relevant literature on neuroendocrine tumors and current treatment strategies for intracranial metastases of neuroendocrine origin.

We are presenting a rare case report that adds on to the scarce literature on methylphenidate-induced chorea. It also challenges the consulting psychiatrists to broaden their differential diagnosis for acute onset of choreiform movement disorders. This unique case intrigues the thought process to consider the interaction of methylphenidate in the presence of cytochrome P450 2D6 and 3A4 inhibitors like methadone.

Objective: There remains a gap in the literature analyzing how categorical variables may affect the highly competitive neurosurgery residency application process for MD Seniors in the United States. We aimed to improve understanding of the impact of medical school prestige and geographic location on candidacy for neurosurgery residency. Methods: Schools were stratified into high and low prestige cohorts based on the U.S. News and World Report Rankings and by geographic location. Publicly available match data displayed by websites of included medical schools from 2016 to 2020 were examined, and neurosurgery residency placement rates were then compared. Analysis was performed using Fisher's exact test and chi-square analysis, with a p-value of 0.05. Results: There were 6685 total matches in the high-prestige cohort and 12,997 total matches in the low-prestige cohort, with 115 (1.72%) and 113 (0.87%) neurosurgery matches, respectively (OR = 2.00, p < 0.0001). Considering geographic location, there were 5244 total matches in the Midwest, 3456 total matches in the West, 4994 total matches in the South, and 6053 total matches in the Northeast, with 51 (0.97%), 24 (0.69%), 83 (1.66%), and 114 (1.88%) being neurosurgery residency placements, respectively (p < 0.0001). Conclusions: Neurosurgery residency placement may be correlated with attending more prestigious medical schools and those located in the Northeast or South United States. Further elucidation of similar variables may prove to be important as neurosurgery residency becomes more competitive and the evaluation process changes.

Primary spine tumors are rare neoplasms that affect about 0.62 per 100,000 individuals in the US. Intramedullary spinal cord tumors (IMSCTs) are the rarest of all primary tumors involving the spine and can cause pain, imbalance, urinary dysfunction and neurological deficits. These types of tumors oftentimes necessitate surgical treatment, yet there is a lack of data on hospital length of stay and complication rates following treatment. Given that treatment candidacy, quality of life, and outcomes are tied so closely to potential for prolonged length of stay and postoperative complications, it is important to better understand the factors that increase the risk of these outcomes in patients with IMSCTs. Methods: The National Surgical Quality Improvement Program (NSQIP) database was queried for all patients undergoing surgery for treatment of intramedullary spinal cord tumors between 2005 and 2017. Univariate and multivariate analysis were performed to assess patient risk factors influencing prolonged length of stay and post-op complications. Results: A total of 638 patients were included in the analysis. Pre-operative American Society of Anesthesiology (ASA) physical status classification of 3 and above (OR 1.89; p = 0.0005), dependent functional status (OR 2.76; p = 0.0035) and transfer from facilities other than home (OR 8.12; p <0.0001) were independent predictors of prolonged length of stay (>5 days). The most commonly reported complications were pneumonia (5.7%), urinary tract infection (9.4%), septic shock (3.8%), superficial incisional infection (5.7%), organ or space infection (5.7%), pulmonary embolism (11.3%), DVT requiring therapy (15.1%) and wound dehiscence (5.7%). Conclusion: Our study demonstrated the significant influence of clinical variables on prolonged hospitalization of IMSCT patients. This should be factored into clinical and surgical decision making and when counseling patients of their expected outcomes. (c) 2021 Published by Elsevier Ltd.

Even though screening mammography has been attributed to decreased mortality in recent decades, breast cancer is one of the leading causes of death among women in the United States. Disruption of screening protocols and variation in the presentation may alter the course of detection and management. We report a case of hormone receptor-positive breast cancer that presented as vague gastrointestinal symptoms in a patient with a delayed workup for a self-discovered breast lump during the coronavirus disease global pandemic. A 48-year-old woman with a history of gastroesophageal reflux and hypertension presented to the emergency department with primary complaints of constipation and abdominal distention with associated flatus and nausea. Vitals were within normal limits, and physical examination was notable for abdominal distention and diffuse tenderness to palpation. Labs demonstrated hypercalcemia and an unremarkable complete blood count. A chest X-ray showed a right hilar mass, and a CT chest revealed multiple lytic bone lesions diffusely scattered throughout the entire skeleton; no hilar mass was noted on the CT chest. A CT scan of the abdomen and pelvis incidentally revealed a right breast mass. A bone marrow biopsy identified invasive ductal carcinoma. Mammography and biopsy of the breast mass identified estrogen receptor/progesterone receptor-positive invasive ductal carcinoma, consistent with the bone marrow biopsy, confirming the diagnosis of metastatic breast cancer. Unpredicted disruptions in screening processes may result in delayed cancer diagnoses. This case illustrates the importance of routine self-breast examinations, screening mammography, and maintaining a broad differential diagnosis.

Introduction: Estimating the risk of extended length of stay (LOS) or non-routine discharge disposition is helpful in surgical decision-making for patients with brain metastases (BM). In 2020, an online calculator was introduced by Khalafallah et al. that stratified the risk of patients with brain tumors based on poor surgical outcomes. We applied the calculator to our population of BM patients to determine its generalizability and validity. Methods: We included BM patients who underwent a cranial procedure between 2015 and 2018 at a single academic institution. Patient age, race, marital status, admission status, KPS score, and medical co-morbidities (5-point modified frailty index (mFI-5)) were included in the analysis. We calculated the areas under the Receiver Operating Characteristics (ROC) curves to determine the validity of the model proposed in predicting extended LOS (>7 days) and need for specialty care at discharge (non-routine discharge disposition). Results: We analyzed 244 patients (mean age 61.2 years (SD 11.1), 57.0% female, and 78.1% Caucasian). The areas under the ROC curves were 0.8427 and 0.8422 for extended LOS and non-routine discharge disposition, suggesting high accuracy of the models for these outcomes. However, the (mFI-5) was not a significant predictor of either outcome in our multivariate analyses. Conclusions: We validated Khalafallah et al.’s predictive models of extended LOS and non-routine discharge disposition in our patient population, which included a broader range of surgical procedures. Further investigation of this model could clarify how the type of neurosurgical procedure influences outcomes, the role of the mFI-5, and its overall generalizability.

OBJECTIVE:To determine how neuropsychiatric comorbidity, modulatory indication, demographics, and other characteristics affect inpatient deep brain stimulation (DBS) outcomes. METHODS:This is a retrospective study of 45 months' worth of data from the National Inpatient Sample. Patients were aged ≥ 18 years old and underwent DBS for Parkinson Disease (PD), essential tremor (ET), general dystonia and related disorders, other movement disorder (non-PD/ET), or obsessive-compulsive disorder (OCD) at a US hospital. Primary endpoints were prolonged length of stay (PLOS), high-end hospital charges (HEHCs), unfavorable disposition, and inpatient complications. Logistic models were constructed with odds ratios under 95% confidence intervals. A p-value of 0.05 determined significance. RESULTS:Of 214,098 records, there were 27,956 eligible patients. Average age was 63.9 ± 11.2 years, 17,769 (63.6%) were male, and 10,182 (36.4%) patients were female. Most of the cohort was White (51.1%), Medicare payer (64.3%), and treated at a large-bed size (80.7%), private non-profit (76.9%), and metro-teaching (94.0%) hospital. Neuropsychiatric comorbidity prevalence ranged from 29.9% to 47.7% depending on indication. Compared with PD, odds of complications and unfavorable disposition were significantly higher with other movement disorders and dystonia, whereas OCD conferred greater risk for HEHCs (p < 0.05). Patients with ET had favorable outcomes. Neuropsychiatric comorbidity, Black race, and Charlson Comorbidity Index > 0 were significantly associated with unfavorable outcomes (p < 0.05). CONCLUSION:The risk of adverse inpatient outcomes for DBS in the United States is independently correlated with non-PD/ET disorders, neuropsychiatric comorbidity, and non-White race, reflecting the heterogeneity and infancy of widespread DBS for these patients.

BACKGROUND:The incidence of metastatic spine disease (MSD) is increasing among cancer patients. Given the poor outcomes and high rates of morbidity associated with MSD, it is important to determine demographic factors that could impact interventions and outcomes for this patient population. The objectives of this study were to compare in-hospital mortality and complication rates, clinical presentation, and interventions between female and male patients diagnosed with MSD.METHODS:Patient data were collected from the United States National Inpatient Sample (NIS) database from the years 2012-2014. Descriptive statistics were used to compare data from 51,800 cases; subsequently, multivariable logistic regression analyses were conducted to assess the effect of gender on outcomes.RESULTS:Males had significantly higher rates of in-hospital mortality (OR 1.30; 95 % CI 1.09-1.56, p = 0.004) and were more likely to have received surgical intervention than females (OR 1.34; 95 % CI 1.16-1.55, p < 0.001). Additionally, female patients were more likely to present with vertebral compression fracture (p < 0.001), while metastatic spinal cord compression (MSCC) and paralysis were more common in male patients (p < 0.001). There was no significant difference in rates of in-hospital complications between female and male patients.CONCLUSION:Given the significant differences in mortality, disease course, treatment, and in-hospital complications between female and male patients diagnosed with MSD, additional prospective studies are necessary to understand how to meaningfully incorporate these differences into clinical care and prognostication going forward.