Hammad Ghanchi

All Publications

• P13BP, a Calpain-2-Mediated Breakdown Product of PTPN13, Is a Novel Blood Biomarker for Traumatic Brain Injury. Journal of neurotrauma Wang, Y., Brazdzionis, J., Dong, F., Patchana, T., Ghanchi, H., Podkovik, S., Wiginton, J. G., Marino, M., Duong, J., Wacker, M., Miulli, D. E., Neeki, M., Bi, X., Baudry, M. 2021; 38 (22): 3077-3085

  Abstract

  Biomarkers play an increasing role in medicinal biology. They are used for diagnosis, management, drug target identification, drug responses, and disease prognosis. We have discovered that calpain-1 and calpain-2 play opposite functions in neurodegeneration, with calpain-1 activation being neuroprotective, while prolonged calpain-2 activation is neurodegenerative. This notion has been validated in several mouse models of acute neuronal injury, in particular in mouse models of traumatic brain injury (TBI) and repeated concussions. We have identified a selective substrate of calpain-2, the tyrosine phosphatase, PTPN13, which is cleaved in brain after TBI. One of the fragments generated by calpain-2, referred to as P13BP, is also found in the blood after TBI both in mice and humans. In humans, P13BP blood levels are significantly correlated with the severity of TBI, as measured by Glasgow Coma Scale scores and loss of consciousness. The results indicate that P13BP represents a novel blood biomarker for TBI.

  View details for DOI 10.1089/neu.2021.0229

  View details for PubMedID 34498916

• Pediatric Temporal Lobe Meningioma With Meningioangiomatosis Mimicking Invasive Meningioma. Cureus Hassan, O., Ghanchi, H., DeLos Reyes, K., Raghavan, R., Minasian, T. 2021; 13 (10): e18819

  Abstract

  Meningiomas combined with meningioangiomatosis (MA-M) present similarly to more invasive lesions because of their appearance on neuroimaging. These lesions are especially rare in pediatric patients and suggestive imaging can help identify them for differential diagnosis. An 11-year-old male child who presented with diplopia and a headache was found to have an edematous invasive appearing temporal lobe mass on magnetic resonance imaging. Despite the lesion's appearance, it was completely resected and found to be a benign MA-M upon histopathologic examination. The present case demonstrated a rare meningioma with meningioangiomatosis that appeared to be a higher grade or invasive lesion upon initial imaging in a pediatric patient. A review of the literature was performed on patients who presented similarly. Despite the rarity of this condition in children, neuroimaging should be carefully examined prior to surgical resection of similar masses in preparation for highly vascular tissue, and post-operative course can be better anticipated when MA-M is considered during differential diagnosis.

  View details for DOI 10.7759/cureus.18819

  View details for PubMedID 34804676

  View details for PubMedCentralID PMC8592784

• Radiolucent carbon fiber-reinforced implants for treatment of spinal tumors- clinical, radiographic, and dosimetric considerations. World neurosurgery Takayanagi, A., Siddiqi, I., Ghanchi, H., Lischalk, J., Vrionis, F., Ratliff, J., Bilsky, M., Hariri, O. R. 2021

  Abstract

  The management of spine tumors is multimodal and personalized to each individual patient. Patients often require radiation therapy after surgical fixation. While titanium implants are used most commonly, they produce significant artifact, leading to decreased confidence in target-volume coverage and normal tissue sparing. Carbon-based materials have been found to have minimal effects on dose-perturbation in postoperative radiation therapy while demonstrating biostability and biocompatibility that is comparable to titanium implants. We conducted a systematic review on carbon-based screw and rod fixation systems in the treatment of spinal tumors utilizing Pubmed and Web of Sciences databases. We reviewed clinical studies with regards to safety of spine fixation with carbon fiber reinforced (CFR) implants, biomechanical studies, as well as radiation and dosimetric studies. The radiolucency of CFR-PEEK implants has potential to benefit spine tumor patients. Clinical studies have demonstrated no increase in complications with implementation of CFR-PEEK implants, and these devices appear to have sufficient stiffness and pullout strength. However, further trials will be necessary in order to determine if there is a clinically significant impact on local tumor control.

  View details for DOI 10.1016/j.wneu.2021.05.100

  View details for PubMedID 34062294

• Diagnosis, Management, and Treatment Options: A Cervical Spine Osteochondroma Meta-Analysis. World neurosurgery Fowler, J., Takayanagi, A., Fiani, B., Cathel, A., Sarhadi, K. J., Arshad, M., Lau, S., Siddiqi, I., Ghanchi, H., Wolberg, A., Hariri, O. 2021; 149: 215-225.e6

  Abstract

  Osteochondroma is described as a capped benign bony neoplasm that forms on the outer surface of bone. These tumors affect nearly 6 million people per year. Although osteochondromas most often involve the appendicular skeleton, many involve the spine, with many cases located in the cervical spine. When osteochondromas involve the spine, they can present with a variety of symptoms, including pain, radiculopathy, and myelopathy, which may necessitate surgical treatment. Spinal osteochondromas can be classified into 2 types: multiple osteochondromas in the context of patients with multiple hereditary exostosis (MHE) and solitary osteochondroma or solitary exostosis (SE). Previous reviews have captured only some of the available literature on cervical osteochondromas and have generally focused on either SE or those associated with MHE. The purpose of our review was to provide an extensive review of all previously reported cervical osteochondromas and to compare osteochondroma characteristics, clinical presentation, and outcomes in the context of MHE and SE.

  View details for DOI 10.1016/j.wneu.2021.01.148

  View details for PubMedID 33561553

• Timing of Chemoradiation in Newly Diagnosed Glioblastoma: Comparative Analysis Between County and Managed Care Health Care Models. World neurosurgery Toor, H., Savla, P., Podkovik, S., Patchana, T., Ghanchi, H., Kashyap, S., Tashjian, V., Miulli, D. 2021; 149: e1038-e1042

  Abstract

  Glioblastoma multiforme (GBM) is a primary brain malignancy with significant morbidity and mortality. The current standard of treatment for GBM is surgery followed by radiotherapy and temozolomide. Despite an established treatment protocol, there exists heterogeneity in outcomes due to patients not receiving all treatments. We analyzed patients in different health care models to investigate this heterogeneity.A retrospective analysis was performed at 2 hospitals in San Bernardino County, California, for patients with newly diagnosed GBM from 2004 to 2019. Patients younger than 18 years of age, with history of low-grade glioma, who had undergone prior treatment, and those lost to follow-up were excluded.A total of 57 patients were included in our study. Chemotherapy was started at 41 ± 30 and 77 ± 68 days in the health maintenance organization (HMO) and county model, respectively (P = 0.050); radiation therapy was started at 46 ± 34 and 85 ± 76 days in the HMO and county models, respectively (P = 0.036). In individuals who underwent both chemotherapy and radiation therapy (XRT), the difference in time to XRT was no longer significant (P = 0.060). Recurrence time was 309 ± 263 and 212 ± 180 days in the HMO and county groups, respectively (P = 0.379). The time to death was 412 ± 285 and 343 ± 304 days for HMO and county models, respectively (P = 0.334).Our study demonstrates a statistically significant difference in time to adjuvant therapies between patients within a county hospital and a managed health care organization. This information has the potential to inform future policies and care coordination for patients within the county model.

  View details for DOI 10.1016/j.wneu.2021.01.023

  View details for PubMedID 33476782

• Osteopathic Manipulative Treatment to Optimize the Glymphatic Environment in Severe Traumatic Brain Injury Measured With Optic Nerve Sheath Diameter, Intracranial Pressure Monitoring, and Neurological Pupil Index. Cureus Kashyap, S., Brazdzionis, J., Savla, P., Berry, J. A., Farr, S., Patchana, T., Majeed, G., Ghanchi, H., Bowen, I., Wacker, M. R., Miulli, D. E. 2021; 13 (3): e13823

  Abstract

  Background Traumatic brain injury (TBI) has a complex pathophysiology that has historically been poorly understood. New evidence on the pathophysiology, molecular biology, and diagnostic studies involved in TBI have shed new light on optimizing rehabilitation and recovery. The goal of this study was to assess the effect of osteopathic manipulative treatment (OMT) on peripheral and central glial lymphatics in patients with severe TBI, brain edema, and elevated intracranial pressure (ICP) by measuring changes in several parameters regularly used in management. Methodology This was a retrospective study at a level II trauma center that occurred in 2018. The study enrolled patients with TBI, increased ICP, or brain edema who had an external ventricular drain placed. Patients previously underwent a 51-minute treatment with OMT with an established protocol. Patients received 51 minutes of OMT to the head, neck, and peripheral lymphatics. The ICP, cerebrospinal fluid (CSF) drainage, optic nerve sheath diameter (ONSD) measured by ultrasonography, and Neurological Pupil Index (NPi) measured by pupillometer were recorded before, during, and after receiving OMT. Results A total of 11 patients were included in the study, and 21 points of data were collected from the patients meeting inclusion criteria who received OMT. There was a mean decrease in the ONSD of 0.62 mm from 6.24 mm to 5.62 mm (P = 0.0001). The mean increase in NPi was 0.18 (P = 0.01). The mean decrease in ICP was 3.33 mmHg (P= 0.0001). There was a significant decrease in CSF output after treatment (P = 0.0001). Each measurement of ICP, ONSD, and NPi demonstrated a decrease in overall CSF volume and pressure after OMT compared to CSF output and ICP prior to OMT. Conclusions This study demonstrates that OMT may help optimize glial lymphatic clearance of CSF and improve brain edema, interstitial waste product removal, NPi, ICP, CSF volume, and ONSD. A holistic approach including OMT may be considered to enhance management in TBI patients. As TBI is a spectrum of disease, utilizing similar techniques may be considered for all forms of TBI including concussions and other diseases with brain edema. The results of this study can better inform future trials to specifically study the effectiveness of OMT in post-concussive treatment and in those with mild-to-moderate TBI.

  View details for DOI 10.7759/cureus.13823

  View details for PubMedID 33859888

  View details for PubMedCentralID PMC8038899

• Resolution of tardive tremor after bilateral subthalamic nucleus deep brain stimulation placement. Surgical neurology international Kashyap, S., Ceponiene, R., Savla, P., Bernstein, J., Ghanchi, H., Ananda, A. 2020; 11: 444

  Abstract

  Tardive tremor (TT) is an underrecognized manifestation of tardive syndrome (TS). In our experience, TT is a rather common manifestation of TS, especially in a setting of treatment with aripiprazole, and is a frequent cause of referrals for the evaluation of idiopathic Parkinson disease. There are reports of successful treatment of tardive orofacial dyskinesia and dystonia with deep brain stimulation (DBS) using globus pallidus interna (GPi) as the primary target, but the literature on subthalamic nucleus (STN) DBS for tardive dyskinesia (TD) is lacking. To the best of our knowledge, there are no reports on DBS treatment of TT.A 75-year-old right-handed female with the medical history of generalized anxiety disorder and major depressive disorder had been treated with thioridazine and citalopram from 1980 till 2010. Around 2008, she developed orolingual dyskinesia. She was started on tetrabenazine in June 2011. She continued to have tremors and developed Parkinsonian gait, both of which worsened overtime. She underwent DBS placement in the left STN in January 2017 with near-complete resolution of her tremors. She underwent right STN implantation in September 2017 with similar improvement in symptoms.While DBS-GPi is the preferred treatment in treating oral TD and dystonia, DBS-STN could be considered a safe and effective target in patients with predominating TT and/or tardive Parkinsonism. This patient saw a marked improvement in her symptoms after implantation of DBS electrodes, without significant relapse or recurrence in the years following implantation.

  View details for DOI 10.25259/SNI_723_2020

  View details for PubMedID 33408929

  View details for PubMedCentralID PMC7771401

• Use of Endovascular Simulator in Training of Neurosurgery Residents - A Review and Single Institution Experience. Cureus Patchana, T., Wiginton, J., Ghanchi, H., Favre, A. W., Tayag, E. C., Schiraldi, M., Miulli, D. E. 2020; 12 (12): e11931

  Abstract

  Simulators for surgical procedures and interventions have undergone significant technological advancement in the past decade and are becoming more commonplace in medical training. Neurosurgery residents across multiple training levels underwent performance evaluation using a neuro-interventional simulator, employing a variety of metrics for assessment. We identified seven core metrics used in the evaluation of neurosurgery residents performing simulated mechanical thrombectomies. Additionally, a systematic PubMed search for studies related to Neurointerventional Radiology training via simulation was performed. The purpose of this study is to examine the validity and benefits of training with these simulation devices and compare our institution's experience. Additionally, an exploration of their applicability to neurosurgery resident training is discussed.

  View details for DOI 10.7759/cureus.11931

  View details for PubMedID 33425512

  View details for PubMedCentralID PMC7785465

• Spinal Arteriovenous Malformation: Case Report and Review of the Literature. Cureus Patchana, T., Savla, P., Taka, T. M., Ghanchi, H., Wiginton, J., Schiraldi, M., Cortez, V. 2020; 12 (11): e11614

  Abstract

  Spinal arteriovenous malformations (AVMs) are a rare form of spinal blood vessel defect that results in vessel engorgement leading to clinical signs secondary to mass effect and ischemia. We present the patient's clinical course following suspicion of spinal AVM along with a review of current classification and imaging modalities.

  View details for DOI 10.7759/cureus.11614

  View details for PubMedID 33364131

  View details for PubMedCentralID PMC7752798

• Generalized Dystonia Treated With Deep Brain Stimulator: An Institutional Single Surgeon Experience. Cureus Ghanchi, H., Bernstein, J. E., Taka, T. M., Patchana, T., Kashyap, S., Hariri, O. R., Jamshidi, A. O., Ananda, A. K. 2020; 12 (10): e10992

  Abstract

  Introduction Dystonia can cause severe disability when left untreated. Once a patient has exhausted medical management, surgical intervention may be the only treatment option. Although not curative, deep brain stimulation has been shown to be beneficial for patients affected by this condition. Our study sought to review patients undergoing deep brain stimulation for medically refractory dystonia to assess outcomes. Methods Our institution's operative database was reviewed retrospectively for all patients undergoing deep brain stimulator placement over the last six years. These medical records were reviewed for the severity of dystonia preoperatively and followed postoperatively for 24 months, focusing on the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Patients with less than two-year postoperative follow-up were excluded from the study. The patients were further stratified by age into Group A, consisting of patients less than 40 years old, and Group B, patients greater than or equal to 40 years old. Other attributes such as age, sex, age of disease onset, disease duration at the time of surgery, genetic tests for dystonia-related genes, and any complication associated with surgery were also reviewed. Results Four hundred fifty-five operative cases for deep brain stimulator placement were reviewed, and 16 patients met inclusion criteria for the study. The mean age for our patient cohort was 43.75 years, with four males and 12 females. The average time from the age of disease onset to time of surgery was 9.7 years for Group A and 10.8 years for Group B; the overall average was 10.3 years. All patients had globus pallidus interna (GPi) as their surgical target. The first incidence of a statistically significant decrease in BFMDRS score was noted at three months postoperatively (p<0.001) when compared to preoperative values. Fourteen patients in our cohort underwent preoperative genetic testing for DYT gene mutations, out of which four were found to have a mutation. Conclusion Our review of outcomes for primary generalized dystonia at our institution found that deep brain stimulator targeting the GPi is safe and effective. We found an overall 88% response rate with younger patients (< 40-year-old) showing a better response at two years than older patients.

  View details for DOI 10.7759/cureus.10992

  View details for PubMedID 33209548

  View details for PubMedCentralID PMC7668228

• Pentobarbital Coma With Therapeutic Hypothermia for Treatment of Refractory Intracranial Hypertension in Traumatic Brain Injury Patients: A Single Institution Experience. Cureus Bernstein, J. E., Ghanchi, H., Kashyap, S., Podkovik, S., Miulli, D. E., Wacker, M. R., Sweiss, R. 2020; 12 (9): e10591

  Abstract

  Introduction Traumatic brain injury (TBI) results in primary and secondary brain injuries. Secondary brain injury can lead to cerebral edema resulting in increased intracranial pressure (ICP) secondary to the rigid encasement of the skull. Increased ICP leads to decreased cerebral perfusion pressure which leads to cerebral ischemia. Refractory intracranial hypertension (RICH) occurs when ICP remains elevated despite first-tier therapies such as head elevation, straightening of the neck, analgesia, sedation, paralytics, cerebrospinal fluid (CSF) drainage, mannitol and/or hypertonic saline administration. If unresponsive to these measures, second-tier therapies such as hypothermia, barbiturate infusion, and/or surgery are employed. Methods This was a retrospective review of patients admitted at Arrowhead Regional Medical Center from 2008 to 2019 for severe TBI who developed RICH requiring placement into a pentobarbital-induced coma with therapeutic hypothermia. Primary endpoints included mortality, good recovery which was designated at Glasgow outcome scale (GOS) of 4 or 5, and improvement in ICP (goal is <20 mmHg). Secondary endpoints included complications, length of intensive care unit (ICU) stay, length of hospital stay, length of pentobarbital coma, length of hypothermia, need for vasopressors, and decompressive surgery versus no decompressive surgery. Results Our study included 18 patients placed in pentobarbital coma with hypothermia for RICH. The overall mortality rate in our study was 50%; with 60% mortality in pentobarbital/hypothermia only group, and 46% mortality in surgery plus pentobarbital/hypothermia group. Maximum ICP prior to pentobarbital/hypothermia was significantly lower in patients who had a prior decompressive craniectomy than in patients who were placed into pentobarbital/hypothermia protocol first (28.3 vs 35.4, p<0.0238). ICP was significantly reduced at 4 hours, 8 hours, 12 hours, 24 hours, and 48 hours after pentobarbital and hypothermia treatment. Initial ICP and maximum ICP prior to pentobarbital/hypothermia was significantly correlated with mortality (p=0.022 and p=0.026). Patients with an ICP>25 mmHg prior to pentobarbital/hypothermia initiation had an increased risk of mortality (p=0.0455). There was no statistically significant difference in mean ICP after 24 hours after pentobarbital/hypothermia protocol in survivors vs non-survivors. Increased time to reach 33°C was associated with increased mortality (r=0.47, p=0.047); with a 10.5-fold increase in mortality for >7 hours (OR 10.5, p=0.039). Conclusion Prolonged cooling time >7 hours was associated with a 10.5-fold increase in mortality and ICP>25 mmHg prior to initiation of pentobarbital and hypothermia is suggestive of a poor response to treatment. We recommend patients with severe TBI who develop RICH should first undergo a 12 x 15 cm decompressive hemicraniectomy because they have better survival and are more likely to have ICP <25 mmHg as the highest elevation of ICP if the ICP were to become and stay elevated again. Pentobarbital and hypothermia should be initiated if the ICP becomes elevated and sustained above 20 mmHg with a prior decompressive hemicraniectomy and refractory to other medical therapies. However, our data suggests that patients are unlikely to survive if there ICP does not decrease to less than 15mmHg at 8 and 12 hours after pentobarbital/hypothermia and remain less than 20 mmHg within first 48 hours.

  View details for DOI 10.7759/cureus.10591

  View details for PubMedID 33110727

  View details for PubMedCentralID PMC7581220

• Racial Disparity Amongst Stroke Patients During the Coronavirus Disease 2019 Pandemic. Cureus Ghanchi, H., Patchana, T., Wiginton, J., Browne, J. D., Ohno, A., Farahmandian, R., Duong, J., Cortez, V., Miulli, D. E. 2020; 12 (9): e10369

  Abstract

  Introduction The global coronavirus disease 2019 (COVID-19) pandemic has had deleterious effects on our healthcare system. Lockdown measures have decreased the number of patients presenting to the hospital for non-respiratory illnesses, such as strokes. Moreover, there appears to be a racial disparity among those afflicted with the virus. We sought to assess whether this disparity also existed for patients presenting with strokes. Methods The Get with the Guidelines National Stroke Database was reviewed to assess patients presenting with a final diagnosis of ischemic stroke, transient ischemic attack (TIA), subarachnoid hemorrhage (SAH), or spontaneous/nontraumatic intraparenchymal hemorrhage (IPH). The period of February - May 2020 was chosen given the surge of patients affected with the virus and national shutdowns. Data from this same time during 2019 was used as the control population. Our hospital numbers and four additional regions were assessed (California hospitals, Pacific State hospitals, Western Region hospitals, and all hospitals in the United States). Patients were categorized by race (White, Black/African American, Asian, Native American, Hispanic) in each cohort. The primary endpoint of this study is to compare whether there was a significant difference in the proportion of patients in each reported racial category presenting with stroke during the COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results A downward trend in total number of patients was noted in all five regional cohorts assessed. A statistically significant increase in the number of Black and Hispanic patients presenting with strokes was noted in California, Pacific hospitals, Western hospitals, and all hospitals in the United States during various months studied comparing 2020 to 2019. A statistically significant increase in the Hispanic population was noted in February and March in all California hospitals (p=0.005 and 0.02, respectively) and Pacific Coast hospitals (p=0.005 and 0.039, respectively). The Western region and all national hospitals noted a significant increase in strokes in the Hispanic population in April (p=0.039 and 0.023, respectively). A statistically significant increase of strokes in the Black population was noted in April in Pacific hospitals, Western region hospitals, and all national hospitals (p=0.039, 0.03, and 0.03, respectively). Conclusion The COVID-19 pandemic has adversely affected certain racial groups more than others. A similar increase is noted in patients presenting with strokes in these specific racial populations. Moreover, lack of testing for the SARS-CoV-2 virus may be missing a possible link between racial disparity for patients infected with the virus and patients presenting with stroke. The authors advocate for widespread testing for all patients to further assess this correlation.

  View details for DOI 10.7759/cureus.10369

  View details for PubMedID 33062492

  View details for PubMedCentralID PMC7549889

• Acquired Holmes Tremor in a Human Immunodeficiency Virus Immune Reconstitution Inflammatory Syndrome Patient Treated with Deep Brain Stimulation. World neurosurgery Ghanchi, H., Siddiqi, I., Patchana, T., Ananda, A. 2020; 141: 253-259

  Abstract

  The authors present a case of a 66-year-old male who was diagnosed with human immunodeficiency virus, and his medical course of highly active antiretroviral therapy was complicated with the development of immune reconstitution inflammatory syndrome, which led to development of movement disorder consisting of right-sided resting tremor, neck dystonia, and jaw clenching.The patient's symptoms resembled that of rubral tremor, and he underwent placement of a deep brain stimulation electrode into the left ventral intermediate nucleus of the thalamus with significant improvement of symptoms.This is the first reported case in the literature of a human immunodeficiency virus-positive patient's treatment course complicated with immune reconstitution inflammatory syndrome with neurologic manifestation, which was refractory to medical therapy and thus treated with deep brain stimulation.

  View details for DOI 10.1016/j.wneu.2020.06.099

  View details for PubMedID 32565375

• Effects of the COVID-19 Pandemic on Stroke Patients. Cureus Ghanchi, H., Takayanagi, A., Savla, P., Hariri, O. R., Tayag, E. C., Schiraldi, M., Jorgensen, L., Miulli, D. E. 2020; 12 (8): e9995

  Abstract

  Introduction The severe acute respiratory syndrome coronavirus 2 (SARS2-CoV-2) induced pandemic (COVID-19 pandemic) has affected healthcare in all aspects, including stroke care. We sought to investigate this effect with analysis of our hospital's stroke treatment protocols as well as stroke volume on state, regional, and national levels. Methods This was a retrospective review of prospectively collected data from our stroke registry to assess the impact of the SARS2-CoV-2 induced pandemic on the volume of stroke patients presenting to our facility. Demographics collected included age, sex, race, National Institute of Health Stroke Scale (NIHSS) on admission, discharge modified Rankin Score (mRS), type of stroke (ischemic, hemorrhagic, or transient ischemic attack), time of symptom onset, and time to initial imaging. Data were also stratified by date and comparison was made between the intra-COVID-period (March and April 2020), pre-COVID period (March and April 2019), and peri-COVID period (January and February 2020). To determine stroke trends on a national level, we utilized the Get with the Guidelines (GWTG) stroke database to compare stroke volumes in the pre-COVID, peri-COVID, and intra-COVID periods between our hospital, all California hospitals, and the West and Pacific regions. Results There was a significant increase in last known well time (LKWT) to arrival to the emergency department (ED) (LKWT to door) as well as time from arrival to the ED to obtaining a computed tomography (CT) of the head (door to CT) in March 2020 compared to 2019 (p=0.0220 and p=0.0475, respectively). There were significantly fewer transient ischemic attacks (TIAs) in California hospitals as well as in March and April 2020 in comparison to January and February 2020 (p=0.0417). Similarly, there were significantly fewer TIAs in March and April 2019 compared to March and April 2020 (p=0.0360). The decrease in TIAs was also seen at our hospital in both time frame comparisons as well as in West Regional Hospitals in March and April 2020 compared to March and April 2019 (p=0.0111, p=0.0215, and p=0.0414, respectively). Conclusion Stroke care has been disrupted by the COVID-19 pandemic worldwide. We identified a delay in LKWT to door as well as time from door to CT in March 2020 compared to March 2019 at our institution. There was a statistically significant decrease in final diagnosis of TIA at our hospital, all California hospitals, and all West Regional hospitals during the March-April 2020 window, suggesting that some patients with minor stroke symptoms may not be presenting to the hospital in the midst of the pandemic. Strategies to minimize delays in care and maximize functional recovery must continue to evolve as new challenges are met during the COVID-19 pandemic.

  View details for DOI 10.7759/cureus.9995

  View details for PubMedID 32983694

  View details for PubMedCentralID PMC7511064

• Subgaleal hematoma evacuation in a pediatric patient: A case report and review of the literature. Surgical neurology international Patchana, T., Ghanchi, H., Taka, T., Calayag, M. 2020; 11: 243

  Abstract

  Subgaleal hematoma (SGH) is generally documented within the neonatal period and is rarely reported as a result of trauma or hair braiding in children. While rare, complications of SGH can result in ophthalmoplegia, proptosis, visual deficit, and corneal ulceration secondary to hematoma extension into the orbit. Although conservative treatment is preferential, expanding SGH should be aspirated to reduce complications associated with further expansion.A 12-year-old African-American female with no recent history of trauma presented with a chief complaint of headache along with a 2-day history of enlarging 2-3 cm ballotable bilateral frontal mass. Hematological workup was negative. The patient's family confirmed a long history of hair braiding. The patient was initially prescribed a period of observation but returned 1-week later with enlarging SGH, necessitating surgical aspiration.SGH is rare past the neonatal period, but can be found in pediatric and adolescent patients secondary to trauma or hair pulling. Standard workup includes evaluation of the patient's hematological profile for bleeding or coagulation deficits, as well as evaluation for child abuse. Although most cases of SGH resolve spontaneously over the course of several weeks, close follow-up is recommended. The authors present a case of a 12-year-old female presenting with enlarging subgaleal hemorrhages who underwent surgical aspiration and drainage without recurrence. A literature review was also conducted with 32 pediatric cases identified, 20 of which were related to hair pulling, combing, or braiding. We review the clinical course, imaging characteristics, surgical management, as well as a review of the literature involving subgaleal hemorrhage in pediatric patients and hair pulling.

  View details for DOI 10.25259/SNI_207_2020

  View details for PubMedID 32905325

  View details for PubMedCentralID PMC7468241

• Pediatric sellar solitary fibrous tumor/ hemangiopericytoma: A rare case report and review of the literature. Surgical neurology international Ghanchi, H., Patchana, T., Christian, E., Li, C., Calayag, M. 2020; 11: 238

  Abstract

  Solitary fibrous tumor (SFT)/hemangiopericytoma (HPC) is a rare tumor which originates from the walls of capillaries and has historically been thought to be able to occur anywhere in the body that blood vessels are found. It is rarely found in the sellar region.InS this report, we present the first case of this tumor occurring in the sellar region of a pediatric patient. This 12-year-old male presented with progressive vision loss which prompted surgical resection after a sellar lesion was discovered on imaging. The initial transsphenoidal approach resulted in subtotal resection and the patient experienced reoccurrence within 3 months. He underwent an orbitozygomatic craniotomy to achieve gross total tumor resection.We conducted a literature review of intracranial SFT/HPC in the pediatric population and found it to be an extremely rare occurrence, with <30 cases reported. The incidence of SFT/HPC occurring in the sellar region for any age group was also found to be a rare entity. Treatment recommendations for this tumor are also scarce, based on retrospective chart reviews from the adult population. The role for adjuvant radiation has mixed results.

  View details for DOI 10.25259/SNI_234_2020

  View details for PubMedID 32874741

  View details for PubMedCentralID PMC7451149

• Spontaneous Spinal Subdural Hematoma Mimicking Myocardial Infarction. Cureus Ghanchi, H., Siddiqi, I., Takayanagi, A., Patchana, T., Fakhoury, F. J. 2020; 12 (7): e9486

  Abstract

  Spontaneous spinal subdural hematomas (SSDHs) are rarely encountered in clinical practice. In this paper, we report a case of a 70-year-old female who presented to the Emergency Department with symptoms of mid-epigastric pain radiating to her mid-scapular region. Her workup demonstrated mildly elevated cardiac troponin I levels and electrocardiogram (ECG) leads V3-V5 ST-depressions. She was subsequently treated through the non-ST elevation myocardial infarction (NSTEMI) protocol and given an antiplatelet agent. The next morning, she developed bilateral lower extremity paresthesias, progressive left lower extremity weakness, and urinary retention. Magnetic resonance imaging (MRI) of the spine demonstrated a hematoma in the thoracic region resulting in spinal cord compression. The patient underwent surgical decompression. After the decompression of the thoracic spinal cord, the patient's neurological symptoms gradually improved and she regained lower extremity function. This report brings to light a very unusual presentation of an uncommon clinical entity. To the best knowledge of the authors, spontaneous SSDH presenting as myocardial injury and subsequently exacerbated by anticoagulation therapy has not been reported in the literature to date.

  View details for DOI 10.7759/cureus.9486

  View details for PubMedID 32874813

  View details for PubMedCentralID PMC7455467

• Case Report: Projectile Into Right Frontal Lobe From a Nail Gun. Cureus Patchana, T., Taka, T. M., Ghanchi, H., Wiginton, J., Wacker, M. 2020; 12 (7): e9460

  Abstract

  We present a case of a nail gun injury penetrating the right maxillary sinus and frontal lobe with complaints of headache and right eye blindness. After surgical removal and treatment, there were no neurological deficits aside from the persistence of right eye blindness that the patient initially presented with. Our report describes the patient's clinical course, the multidisciplinary medical and surgical management, along with the clinical workup and important mental health considerations for patients presenting with intracranial nail gun injuries.

  View details for DOI 10.7759/cureus.9460

  View details for PubMedID 32874792

  View details for PubMedCentralID PMC7455395

• Primary Angiitis of the Central Nervous System Presenting as a Cerebral Mass Lesion: A Case Report and Literature Review. Cureus Bernstein, J. E., Podkovik, S., Kashyap, S., Ghanchi, H., Ananda, A. K. 2020; 12 (6): e8511

  Abstract

  Primary angiitis of the central nervous system (PACNS) is a rare form of vasculitis and is confined entirely to the central nervous system (CNS)without systemic involvement. We report a rare case of PACNS in a 39-year-old female with new onset seizures and a right frontal enhancing mass. Initially the patient was thought to have a high-grade glioma and thus underwent a right frontal craniotomy for resection of right frontal mass. Intraoperatively, two fresh tissue samples were sent for intraoperative consultation. Sample 1 showed predominantly necrotic tissue and scant glial cells while sample 2 revealed glial tissue favoring gliosis versus low-grade neoplasm with necrosis and a few acute inflammatory cells. Final pathological diagnosis was consistent with PACNS. Postoperatively, the patient recovered well from surgery with no neurological deficits and was discharged on postoperative day 3. Two weeks after surgery the patient was started on cyclophosphamide and prednisone by Rheumatology. At one month follow up, the patient remained asymptomatic and seizure free.

  View details for DOI 10.7759/cureus.8511

  View details for PubMedID 32656027

  View details for PubMedCentralID PMC7346301

• The Unsuccessful Twiddler: A Case of Twiddler's Syndrome Without Deep Brain Stimulator Lead Breakage. Cureus Ghanchi, H., Taka, T. M., Bernstein, J. E., Kashyap, S., Ananda, A. K. 2020; 12 (4): e7786

  Abstract

  The authors present the case of a 78-year-old right-handed female with a past medical history of Parkinson's disease, treated with implantation of a left-sided subthalamic nucleus St. Jude Medical Infinity® (Abbott Medical, Austin, TX) deep brain stimulator, who presented with lead-associated discomfort, or "bowstringing". Further investigation by chest X-ray revealed an extensive case of distal lead coiling. However, it was surprising that, despite the extensive coiling, the lead stayed intact without hardware failure as proven by patient remaining asymptomatic from her Parkinson's disease and intraoperative impedance testing demonstrating normal results. After revision surgery, the patient remained asymptomatic. Due to paucity of cases of this disease in the literature, specific predictive risk factors are not known, but certain patient characteristics may help take precautions.

  View details for DOI 10.7759/cureus.7786

  View details for PubMedID 32461858

  View details for PubMedCentralID PMC7243634

• Increased Brain Tissue Oxygen Monitoring Threshold to Improve Hospital Course in Traumatic Brain Injury Patients. Cureus Patchana, T., Wiginton, J., Brazdzionis, J., Ghanchi, H., Zampella, B., Toor, H., Dorkoski, R., Mannickarottu, A., Wacker, M., Sweiss, R., Miulli, D. E. 2020; 12 (2): e7115

  Abstract

  Introduction This article is a retrospective analysis of the neurosurgical census at our institution to determine an optimal threshold for brain tissue oxygenation (PbtO2). The use of brain tissue oxygen monitoring has been in place for approximately three decades but data suggesting optimal thresholds to improve outcomes have been lacking. Though there are multiple modalities to monitor cerebral oxygenation, the monitoring of brain tissue oxygen tension has been deemed the gold standard. Still, it is not clear exactly how reductions in PbtO2 should be treated or what appropriate thresholds to treat might be. The aim of our study was to determine if our threshold of 28 mmHg for a good functional outcome could be correlated to the Glasgow Coma Scale (GCS) and Glasgow Outcome Scale (GOS). Methods A retrospective analysis of the Arrowhead Regional Medical Center (ARMC) Neurosurgery Census was performed. Patients from 2017-2019 who had placement of Licox® cerebral oxygen monitoring sensors (Integra® Lifesciences, Plainsboro Township, New Jersey) were included in the analysis. Fifteen patients were consecutively identified, all of which presented with traumatic brain injury (TBI). Data on age, gender, days in the intensive care unit (ICU), days before discharge or end of medical care, admission GCS, hospital length of stay, GOS, maximum and minimum PbtO2 values for five days following insertion, minimum and maximum intracranial pressures (ICPs), and brain temperature were included for analysis. Patient data were separated into two groups; those with consistently higher PbtO2 scores (≥ 28 mmHg; n = 7) and those with inconsistent/lower PbtO2 scores (< 28 mmHg; n = 8). Standard student t-tests were used to find potential statistical differences between the groups (α = 0.05). Results There were seven patients in the consistently high PbtO2 category (≥ 28 mmHg) and eight patients in the inconsistent/low PbtO2 category (<28 mmHg). The average maximum and minimum PbtO2 for the group displaying worse outcomes (as defined by GCS/GOS) was 23.0 mmHg and 14 mmHg, respectively. Those with consistent Day 2 PbtO2 scores of ≥ 28 mmHg had significantly higher GCS scores at discharge/end of medical care (p < 0.05). Average GCS for the patient group with >28 mmHg PbtO2 averaged over Days 2-5 group was 11.4 (n=7). Average GCS for the <28 group was 7.0 (n=8). The GCS for the >28 group was 63% higher than found in the <28 group (p = 0.03). GOS scores were significantly higher in those with consistently higher PbtO2 (≥ 28) than those with lower PbtO2 scores (< 28). The averages were 3.5 in the higher PbtO2 group as compared to 2 in the lower PbtO2 group. Conclusion Along with ICP monitors and monitoring in the assessment of CPP, brain tissue oxygenation allows yet another metric by which to optimize treatment in TBI patients. At our institution, a PbtO2 level of ≥ 28 mmHg is targeted in order to facilitate a good functional outcome in TBI patients. Keeping patients at this level improves GCS and GOS at discharge/end of medical treatment.

  View details for DOI 10.7759/cureus.7115

  View details for PubMedID 32257661

  View details for PubMedCentralID PMC7101240

• Cervical osteochondroma: surgical planning. Spinal cord series and cases Fowler, J. n., Takayanagi, A. n., Siddiqi, I. n., Ghanchi, H. n., Siddiqi, J. n., Veeravagu, A. n., Desai, A. n., Vrionis, F. n., Hariri, O. R. 2020; 6 (1): 44

  Abstract

  Osteochondromas are benign bone tumors which occur as solitary lesions or as part of the syndrome multiple hereditary exostoses. While most osteochondromas occur in the appendicular skeleton, they can also occur in the spine. Most lesions are asymptomatic however some may encroach on the spinal cord or the nerve roots causing neurological symptoms. While most patients with osteochondromas undergo laminectomy without fusion, laminectomy with fusion is indicated in appropriately selected cases of spinal decompression.We present a case of a 32-year-old male with history of multiple hereditary exostoses who presented with symptoms of bilateral upper extremity numbness and complaints of gait imbalance and multiple falls. He reported rapid progression of his symptoms during the 10 days before presentation. Computed tomography of the cervical spine revealed a lobulated bony tumor along the inner margin of the cervical 4 lamina. He underwent cervical 3 and 4 laminectomies, partial cervical 2 and 5 laminectomies and cervical 3-5 mass screw placement. Pathology was consistent with osteochondroma. The patient's symptoms had markedly improved at follow-up.According to our literature review, osteochondromas most commonly occur at cervical 2 and cervical 5. We present a case of an osteochondroma at a less common level, cervical 4. While most osteochondromas are addressed with laminectomy without arthrodesis, the decision of whether arthrodesis is necessary should be considered in all patients with osteochondroma as with any cervical decompression.

  View details for DOI 10.1038/s41394-020-0292-7

  View details for PubMedID 32467563

• Diagnosis of Rhinocerebral Mucormycosis by Treatment of Cavernous Right Internal Carotid Artery Occlusion With Mechanical Thrombectomy: Special Case Presentation and Literature Review. Frontiers in neurology Kashyap, S., Bernstein, J., Ghanchi, H., Bowen, I., Cortez, V. 2019; 10: 264

  Abstract

  Background: Mucormycosis is a rapidly progressive, angioinvasive fungal infection that has a predilection for the paranasal sinuses and adjacent mucosa. Rhinocerebral mucormycosis (RCM) is the most common form and is known to invade the skull base and its associated blood vessels-leading to mycotic aneurysms, ischemic infarcts, and intracerebral hemorrhage. There are documented cases of mechanical thrombectomy in ischemic stroke due to RCM, however, there are no known cases that were diagnosed primarily by histological and pathological analysis of the embolus. We present a case of treatment of large vessel occlusion that led to the diagnosis and treatment of RCM. Case Presentation: A 21 year-old male inmate with history of type 1 diabetes presented with generalized weakness, abdominal pain, right eye blindness, and ophthalmoplegia after an assault in prison. He underwent treatment for diabetic ketoacidosis, but subsequently developed left hemiplegia and was found to have complete occlusion of his right internal carotid artery. He underwent successful mechanical thrombectomy and pathological analysis of the embolus revealed a diagnosis of mucormycosis. He completed a course of amphotericin B, micafungin, and posaconazole. With the aid of acute rehabilitation he achieved a modified Rankin score of 2. Discussion: We review the pathogenesis, diagnosis, and treatment of RCM. A comprehensive multidisciplinary approach is critical in the management of this often-fatal disease. Early diagnosis and treatment are essential in RCM as delaying treatment by more than 6 days significantly increases mortality. Treatment includes surgical debridement and intravenous antifungal therapy (amphotericin B + micafungin or caspofungin) for a minimum of 6-8 weeks.

  View details for DOI 10.3389/fneur.2019.00264

  View details for PubMedID 30972005

  View details for PubMedCentralID PMC6443639

• Bedside Intracranial Hematoma Evacuation and Intraparenchymal Drain Placement for Spontaneous Intracranial Hematoma Larger than 30cc in Volume: Institutional Experience and Patient Outcomes. Journal of neurosciences in rural practice Carson, T., Ghanchi, H., Billings, M., Cortez, V., Sweiss, R., Miulli, D. 2018; 9 (4): 582-586

  Abstract

  Intracranial hemorrhage (ICH) accounts for significant morbidity and mortality in the United States. Many studies have looked at the benefits of surgical intervention for ICH. Recent results for Minimally Invasive Surgery Plus Recombinant Tissue-type Plasminogen Activator for Intracerebral Hemorrhage-II trials have shown promise for a minimally invasive clot evaluation on improving perihematomal edema. Often rural or busy county medical centers may not have the resources available for immediate operative procedures that are nonemergent. In addition, ICH disproportionally affects the elderly which may not be stable for general anesthetics. This study looks at a minimally invasive bedside approach under conscious sedation for evacuation of ICH.Placement of the intraparenchymal hemorrhage drain utilizes bony anatomical landmarks referenced from computed tomography (CT) head to localize the entry point for the trajectory of drain placement. Using the hand twist drill intracranial access is gained the clot accessed with a brain needle. A Frazier suction tip with stylet is inserted along the tract then the stylet is removed. The clot is then aspirated, and suction is then turned off, and Frazier sucker is removed. A trauma style ventricular catheter is then passed down the tract into the center of hematoma and if no active bleeding is noted on postplacement CT and catheter is in an acceptable position then 2 mg recombinant tissue plasminogen activator are administered through the catheter and remaining clot is allowed to drain over days.A total of 12 patients were treated from October 2014 to December 2017. The average treatment was 6.4 days. The glascow coma scale score improved on an average from 8 to 11 posttreatment with a value of P is 0.094. The average clot size was reduced by 77% with a value of P = 0.0000035. All patients experienced an improvement in expected mortality when compared to the predicted ICH score.The results for our series of 12 patients show a trend toward improvement in Glasgow Coma Scale after treatment with minimally invasive intraparenchymal clot evacuation and drain placement at the bedside; although, it did not reach statistical significance. There was a reduction in clot size after treatment, which was statistically significant. In addition, the 30-day mortality actually observed in our patients was lower than that estimated using ICH score. Based on our experience, this procedure can be safely performed at the bedside and has resulted in better outcomes for these patients.

  View details for DOI 10.4103/jnrp.jnrp_93_18

  View details for PubMedID 30271055

  View details for PubMedCentralID PMC6126292

• Novel Method of Non-contact Remote Measurement of Neuronal Electrical Activity. Cureus Carson, T. A., Ghanchi, H., Toor, H., Majeed, G., Wiginton, J. G., Zhang, Y., Miulli, D. E. 2018; 10 (9): e3384

  Abstract

  Measuring the electrical potential of a neuron cell currently requires direct contact with the cell surface. This method requires invasive probing and is limited by the deflection of electricity from baseline. From a clinical perspective, the electrical potential of the brain's surface can only be measured to a depth of one centimeter using an electroencephalogram (EEG), however, it cannot measure much deeper structures. In this trial, we attempt a novel method to remotely record the electromagnetic field (EMF) of action potential provoked from hippocampal neurons without contact. A bipolar stimulating electrode was placed in contact with the CA1 region of viable hippocampal slice from donor mice. The specimen was bathed in artifical cerebrospinal fluid (aCSF) to simulate in vivo conditions. This setup was then placed into a magnetic shielded tube. Very low-frequency EMF sensors were used to obtain recordings. The impedance of the aCSF and hippocampal slice were measured after each stimulation individually and in combination. An electromagnetic signal was detected in three out of four scenarios: (a) aCSF alone with electrical stimulus without a hippocampal slice, (b) Hippocampal slice in aCSF without electrical stimulus and, (c) Hippocampal slice in aCSF with an electric stimulus applied. Therefore, our trial suggests that EMFs from neuronal tissue can be recorded through non-invasive non-contact sensors.

  View details for DOI 10.7759/cureus.3384

  View details for PubMedID 30519523

  View details for PubMedCentralID PMC6263614

• Metastatic Nongestational Choriocarcinoma to the Brain: Case Report and Proposed Treatment Recommendations. World neurosurgery Duong, J., Ghanchi, H., Miulli, D., Kahlon, A. 2018; 115: 170-175

  Abstract

  Nongestational choriocarcinoma (NGC) is a rare germ cell tumor, accounting for <0.6% of all gestational tumors, and has a poor prognosis when metastasized. NGC with metastasis to the brain is reported even less frequently. Gestational choriocarcinoma (GC) when metastasized to the brain has a higher morbidity and mortality but has been known to be a chemosensitive and radiosensitive lesion, and NGC is chemoresistant with an even worse prognosis. Currently, there is no consensus for treatment for metastatic NGC to the brain.This 66-year-old postmenopausal female presented with left upper extremity weakness more pronounced in her hand and a workup demonstrating a hemorrhagic lesion over the right frontal parietal lobe. Her metastatic workup was negative, leading to a craniotomy for resection of the mass. The pathology was consistent with metastatic GC of nongestational origin.Because of its chemosensitive nature, reports of optimal metastatic GC treatment include radiation alone, chemotherapy without radiation, surgical resection, or combined multimodal therapy. No recommendations for NGC metastasized to the brain have been reported. We propose a systematic workup for hemorrhagic brain lesions to include the proposed imaging modalities and serum markers, including β-human chorionic gonadotropin, to aid early diagnosis. Based on a review of the literature, we recommend surgical resection with adjuvant therapy for accessible symptomatic metastatic GC and NGC to the brain for optimal patient outcomes. Chemotherapy and radiation alone without surgical resection can be considered for asymptomatic GC metastasis to the brain.

  View details for DOI 10.1016/j.wneu.2018.04.050

  View details for PubMedID 29678709

• Multiple Extradural Spinal Meningiomas in a Patient with Acquired Immunodeficiency Syndrome: Case Report and Literature Review. World neurosurgery Ghanchi, H. n., Hariri, O. R., Takayanagi, A. n., Li, G. n. 2018

  View details for PubMedID 29966786

• Abdominal pseudocyst as a complication of ventriculoperitoneal shunt placement: Review of the literature and a proposed algorithm for treatment using 4 illustrative cases. Surgical neurology international Kashyap, S., Ghanchi, H., Minasian, T., Dong, F., Miulli, D. 2017; 8: 78

  Abstract

  Ventriculoperitoneal (VP) shunt placement is one of the most commonly performed procedures in neurosurgery. One rare complication is the formation of an abdominal pseudocyst, which can cause shunt malfunction.We present four unique cases of abdominal pseudocyst formation. Our first patient initially presented with a right upper quadrant pseudocyst. Shunt was externalized and the distal end was revised with placement of catheter on the opposite side. He developed another pseudocyst within 5 months of shunt revision and developed another shunt failure. Our second patient had a history of shunt revisions and a known pseudocyst, presented with small bowel obstruction, and underwent laparotomy for the lysis of adhesions with improvement in his symptoms. After multiple readmissions for the same problem, it was thought that the pseudocyst was causing gastric outlet obstruction and his VP shunt was converted into a ventriculopleural shunt followed by percutaneous drainage of his pseudocyst. Our third patient developed hydrocephalus secondary to cryptococcal meningitis. He developed abdominal pain secondary to an abdominal pseudocyst, which was drained percutaneously with relief of symptoms. The fourth patient had a history of multiple shunt revisions and a previous percutaneous pseudocyst drainage that recurred with cellulitis and abscess secondary to hardware infection.Abdominal pseudocysts are a rare but important complication of VP shunt placement. Treatment depends on etiology, patient presentation, and clinical manifestations. Techniques for revision include distal repositioning of peritoneal catheter, revision of catheter into pleural space or right atrium, or removal of the shunt completely.

  View details for DOI 10.4103/2152-7806.206007

  View details for PubMedID 28584681

  View details for PubMedCentralID PMC5445654

• Unusual Metastasis of Papillary Thyroid Cancer to the Thoracic Spine: A Case Report, New Surgical Management Proposal, and Review of the Literature. Cureus Takayanagi, A., Hariri, O., Ghanchi, H., Miulli, D. E., Siddiqi, J., Vrionis, F., Asgarzadie, F. 2017; 9 (4)

  Abstract

  Papillary thyroid carcinoma (PTC) is significantly more common than follicular thyroid carcinoma (FTC), yet FTC has a much higher tendency to metastasize to the spinal column. We present a rare case of a metastatic thoracic spinal column lesion originating from the PTC. Thyroid carcinoma is known to be highly vascular with a significant tendency to hemorrhage during surgical resection. This increased tendency to hemorrhage leads to unanticipated intraoperative risks when the type of cancer is not diagnosed before surgical resection. Complications related to intraoperative bleeding can be prevented by visualization using angiography and preoperative embolization. The type of cancer is ideally diagnosed before tumor resection either by the standard metastatic workup or histologically after the biopsy. However, limitations exist in these methods, therefore, hypervascular tumors such as metastatic thyroid cancer can go undiagnosed until after surgical resection. In addition to our case report, we present a review of the literature regarding diagnostic and treatment strategies for hypervascular thyroid tumors and propose a new algorithm for the surgical management of spinal tumors with an unknown origin for optimization of preoperative and perioperative care.

  View details for DOI 10.7759/cureus.1132

  View details for PubMedID 28473950

  View details for PubMedCentralID PMC5415380