Several studies have indicated that 30-day morbidity and mortality risk is higher among pediatric... more Several studies have indicated that 30-day morbidity and mortality risk is higher among pediatric and adult patients who are admitted on the weekends. This "weekend effect" has been observed among patients admitted with and for a variety of diagnoses and procedures, respectively, including myocardial infarction, pulmonary embolism, ruptured abdominal aortic aneurysm, stroke, peptic ulcer disease, and pediatric surgery. We sought to compare morbidity and mortality outcomes for emergent pediatric neurosurgical procedures done on the weekend or after-hours with emergent surgical procedures performed during regular weekday "business hours." We conducted a retrospective collection of data. A total of 710 urgent or emergent neurosurgical procedures between December 1, 2011 and August 20, 2014 at Texas Children's Hospital in children less than 18 years of age were performed. These surgical occurrences were then stratified into 3 groups: weekday regular-hours; weekda...
Endoscopic third ventriculostomy (ETV) is an established and effective treatment for obstructive ... more Endoscopic third ventriculostomy (ETV) is an established and effective treatment for obstructive hydrocephalus. In its most common application, surgeons plan their entry point and endoscope trajectory for the procedure based on anatomic landmarks, then free-handedly control the endoscope. We have introduced the Rosa robot assistance to our ETV procedure to stereotactically optimize endoscope trajectories, to reduce risk of traction on neural structures by the endoscope, and to provide a stable mechanical holder of the endoscope. Here, we present our series of Rosa robot-assisted ETVs. At our institution, we performed Rosa robot-assisted ETVs on 6 consecutive subjects within a 3-month period. Patients had to have a favorable expected response to ETV (ETV success score = 70) without additional endoscopic procedures (eg, choroid plexus cauterization, septum pellucidum fenestration). The modality of image registration (CT, MRI, surface mapping, or bone fiducials) was dependent on the ca...
Extracellular vesicles (EVs) are cell-secreted vesicles that range from 30-2000 nm in size. These... more Extracellular vesicles (EVs) are cell-secreted vesicles that range from 30-2000 nm in size. These vesicles are secreted by both normal and neoplastic cells. Physiologically, EVs serve multiple critical biologic functions, including cellular remodeling, intracellular communication, modulation of the tumor microenvironment and regulation of immune function. Because EVs contain genetic and proteomic contents that reflect the cell of origin, it is possible to detect tumor-specific material in EVs secreted by cancer cells. Importantly, EVs secreted by cancer cells transgress anatomic compartments and can be detected in the blood, cerebrospinal fluid, and other biofluids of cancer patients. In this context, there is a growing interest in analyzing EVs from the biofluid of cancer patients as a means of disease diagnosis and therapeutic monitoring. In this article, we review the development of EVs as a diagnostic platform for the most common form of brain cancer, glioblastoma, discuss potential clinical translational opportunities and identify the central challenges associated with future clinical applications.
Between 2005 and 2010, we treated patients with hydrocephalus related to cerebral metastases, who... more Between 2005 and 2010, we treated patients with hydrocephalus related to cerebral metastases, who were not good candidates for surgical resection by either endoscopic third ventriculostomy (ETV) or ventriculoperitoneal shunting (VPS). Patients were excluded from ETV if they had a clinical history suggestive of non-obstructive hydrocephalus, including: (1) history of infection or ventricular hemorrhage and (2) leptomeningeal carcinomatosis. The rest of the patients were treated with VPS. We analyzed the clinical outcome of these patient cohorts, to determine whether the efficacy of VPS was compromised due to a history of infection, ventricular hemorrhage, or leptomeningeal carcinomatosis, and compared these results to those patients who underwent ETV. Sixteen patients were treated with ETV and 36 patients were treated with VPS. The overall efficacy of symptomatic palliation was comparable in the ETV and VPS patients (ETV = 69%, VPS = 75%). In both groups, patients with more severe hydrocephalic symptoms such as nausea, vomiting, and lethargy were more likely to benefit from the procedure. The overall complication rate for the two groups was comparable (ETV = 12.6%, VPS = 19.4%), although the spectrum of complications differed. The overall survival, initial Karnofsky performance status (KPS), and three-month KPS, were similarly comparable (median survival: ETV 3 months, VPS 5.5 months; initial KPS: ETV = 66 ± 7, VPS = 69 ± 12; 3 months KPS: ETV = 86 ± 7, KPS = 84 ± 12). VPS remains a reasonable option for poor RPA grade metastasis patients with hydrocephalus, even in the setting of a previous infection, hemorrhage, or in those with leptomeningeal disease. Optimal treatment of this population will involve the judicious consideration of the relative merits of VPS and ETV.
The ubiquitin-dependent degradation of a test protein beta-galactosidase (beta gal) is preceded b... more The ubiquitin-dependent degradation of a test protein beta-galactosidase (beta gal) is preceded by ubiquitination of beta gal. The many (from 1 to more than 20) ubiquitin moieties attached to a molecule of beta gal occur as an ordered chain of branched ubiquitin-ubiquitin conjugates in which the carboxyl-terminal Gly76 of one ubiquitin is jointed to the internal Lys48 of an adjacent ubiquitin. This multiubiquitin chain is linked to one of two specific Lys residues in beta gal. These same Lys residues have been identified by molecular genetic analysis as components of the aminoterminal degradation signal in beta gal. The experiments with ubiquitin mutated at its Lys48 residue indicate that the multiubiquitin chain in a targeted protein is essential for the degradation of the protein.
ABSTRACT INTRODUCTION: Object: To overcome the temporal and spacial limitations of classical subc... more ABSTRACT INTRODUCTION: Object: To overcome the temporal and spacial limitations of classical subcortical mapping of the corticospinal tract. We evaluated the feasibility and safety of continuous and dynamic subcortical motor mapping especially at low motor thresholds. METHODS: We prospectively studied 69 patients who underwent tumor surgery adjacent to the CST with simultaneous subcortical monopolar motor mapping. Continuous (temporal coverage) and dynamic (spacial coverage) mapping was technically realized by integrating the mapping probe at the tip of a new suction device with the concept that this device will be in contact with the tissue where the resection is performed. Motor function was assessed 1 day after surgery, at discharge, and at 3 months. RESULTS: The initial evaluation in 24 patients showed a 1:1 correlation of MTs for stimulation sites simultaneously mapped with the new suction mapping device and the classic fingerstick probe (74 stimulation points, r = 0.996, P < .001). Thereafter, the fingerstick probe was no longer used and mapping was performed only using the continuous dynamic technique. All procedures were technically successful. Lowest individual motor thresholds (MTs) were as follows (MT, number of patients): >20 mA, n = 7; 11-20 mA, n = 13; 6-10 mA, n = 8; 4-5 mA, n = 17; 1-3 mA, n = 24. At 3 months, 2 patients had a persisting postoperative motor deficit (3%), both were caused by a vascular injury. There was no permanent motor deficit caused by a mechanical injury of the CST. CONCLUSION: Continuous dynamic mapping was found to be a feasible and ergonomic technique of localizing the exact site and distance to the CST. The acoustic feedback and the ability to continuously stimulate the tissue exactly at the site of tissue removal improves the accuracy of mapping especially at low (<5 mA) stimulation intensities. This new technique may increase the safety of motor eloquent tumor surgery. Copyright (C) by the Congress of Neurological Surgeons
Hospital readmission within 30 days of discharge is a major contributor to the high cost of healt... more Hospital readmission within 30 days of discharge is a major contributor to the high cost of health care in the US and is also a major indicator of patient care quality. The purpose of this study was to investigate the incidence, causes, and predictors of 30-day readmission following craniotomy for malignant supratentorial tumor resection. The longitudinal California Office of Statewide Health Planning & Development inpatient-discharge administrative database is a data set that consists of 100% of all inpatient hospitalizations within the state of California and allows each patient to be followed throughout multiple inpatient hospital stays, across multiple institutions, and over multiple years (from 1995 to 2010). This database was used to identify patients who underwent a craniotomy for resection of primary malignant brain tumors. Causes for unplanned 30-day readmission were identified by principle ICD-9 diagnosis code and multivariate analysis was used to determine the independent effect of various patient factors on 30-day readmissions. A total of 18,506 patients received a craniotomy for the treatment of primary malignant brain tumors within the state of California between 1995 and 2010. Four hundred ten patients (2.2%) died during the index surgical admission, 13,586 patients (73.4%) were discharged home, and 4510 patients (24.4%) were transferred to another facility. Among patients discharged home, 1790 patients (13.2%) were readmitted at least once within 30 days of discharge, with 27% of readmissions occurring at a different hospital than the initial surgical institution. The most common reasons for readmission were new onset seizure and convulsive disorder (20.9%), surgical infection of the CNS (14.5%), and new onset of a motor deficit (12.8%). Medi-Cal beneficiaries were at increased odds for readmission relative to privately insured patients (OR 1.52, 95% CI 1.20-1.93). Patients with a history of prior myocardial infarction were at an increased risk of readmission (OR 1.64, 95% CI 1.06-2.54) as were patients who developed hydrocephalus (OR 1.58, 95% CI 1.20-2.07) or venous complications during index surgical admission (OR 3.88, 95% CI 1.84-8.18). Using administrative data, this study demonstrates a baseline glioma surgery 30-day readmission rate of 13.2% in California for patients who are initially discharged home. This paper highlights the medical histories, perioperative complications, and patient demographic groups that are at an increased risk for readmission within 30 days of home discharge. An analysis of conditions present on readmission that were not present at the index surgical admission, such as infection and seizures, suggests that some readmissions may be preventable. Discharge planning strategies aimed at reducing readmission rates in neurosurgical practice should focus on patient groups at high risk for readmission and comprehensive discharge planning protocols should be implemented to specifically target the mitigation of potentially preventable conditions that are highly associated with readmission.
Glioma is the most common brain tumor. For the more aggressive form, glioblastoma, standard treat... more Glioma is the most common brain tumor. For the more aggressive form, glioblastoma, standard treatment includes surgical resection, irradiation with adjuvant temozolomide and, on recurrence, experimental chemotherapy. However, the survival of patients remains poor. There is a critical need for minimally invasive biomarkers for diagnosis and as measures of response to therapeutic interventions. Glioma shed extracellular vesicles (EVs), which invade the surrounding tissue and circulate within both the cerebrospinal fluid and the systemic circulation. These tumor-derived EVs and their content serve as an attractive source of biomarkers. In this review, we discuss the current state of the art of biomarkers for glioma with emphasis on their EV derivation.
Craniofacial procedures may be needed to address symptomatic intracranial hypertension. The autho... more Craniofacial procedures may be needed to address symptomatic intracranial hypertension. The authors review their institutional experience in the treatment of children with symptomatic increased intracranial pressure (ICP) utilizing craniofacial reconstructive procedures. The senior authors' (HSM, SRC) craniofacial experience of 222 patients over a 7-year period from 2000 to 2007 at a single institution (Rady Children's Hospital, San Diego) is reviewed. Seventeen patients were identified who were felt to be candidates for craniofacial surgery with symptomatic increased ICP. Patient diagnoses included single-suture craniosynostosis, craniofacial dysostoses, shunt-induced craniostenosis, and shunt-associated intracranial hypertension (slit-ventricle syndrome). Seventeen patients underwent 21 craniofacial procedures. Age at surgery ranged from 3 months to 13 years with a mean of 5 years. Preoperative symptoms and signs included headaches, unexplained irritability, seizures, papilledema, and visual loss. All patients had diagnostic neuroimaging. Seven patients had preoperative invasive ICP measurements. Surgery was deferred on three of these patients based on these measurements. The mean total operative (including anesthetic preparation) and surgical times were 3 h 12 min and 2 h 20 min, respectively. Percentage operative blood loss averaged 11.3%. In six procedures, no transfusions were required. Average hospital stay was 4 days. There was no perioperative mortality or significant surgery associated morbidity. All patients have had postoperative clinical improvement in signs and symptoms of increased ICP. Using modern diagnostic and surgical techniques, including invasive ICP monitoring, increased intracranial pressure can be successfully managed by an experienced, multidisciplinary, craniofacial team. Our treatment paradigm and operative management scheme is discussed.
Several studies have indicated that 30-day morbidity and mortality risk is higher among pediatric... more Several studies have indicated that 30-day morbidity and mortality risk is higher among pediatric and adult patients who are admitted on the weekends. This "weekend effect" has been observed among patients admitted with and for a variety of diagnoses and procedures, respectively, including myocardial infarction, pulmonary embolism, ruptured abdominal aortic aneurysm, stroke, peptic ulcer disease, and pediatric surgery. We sought to compare morbidity and mortality outcomes for emergent pediatric neurosurgical procedures done on the weekend or after-hours with emergent surgical procedures performed during regular weekday "business hours." We conducted a retrospective collection of data. A total of 710 urgent or emergent neurosurgical procedures between December 1, 2011 and August 20, 2014 at Texas Children's Hospital in children less than 18 years of age were performed. These surgical occurrences were then stratified into 3 groups: weekday regular-hours; weekda...
Endoscopic third ventriculostomy (ETV) is an established and effective treatment for obstructive ... more Endoscopic third ventriculostomy (ETV) is an established and effective treatment for obstructive hydrocephalus. In its most common application, surgeons plan their entry point and endoscope trajectory for the procedure based on anatomic landmarks, then free-handedly control the endoscope. We have introduced the Rosa robot assistance to our ETV procedure to stereotactically optimize endoscope trajectories, to reduce risk of traction on neural structures by the endoscope, and to provide a stable mechanical holder of the endoscope. Here, we present our series of Rosa robot-assisted ETVs. At our institution, we performed Rosa robot-assisted ETVs on 6 consecutive subjects within a 3-month period. Patients had to have a favorable expected response to ETV (ETV success score = 70) without additional endoscopic procedures (eg, choroid plexus cauterization, septum pellucidum fenestration). The modality of image registration (CT, MRI, surface mapping, or bone fiducials) was dependent on the ca...
Extracellular vesicles (EVs) are cell-secreted vesicles that range from 30-2000 nm in size. These... more Extracellular vesicles (EVs) are cell-secreted vesicles that range from 30-2000 nm in size. These vesicles are secreted by both normal and neoplastic cells. Physiologically, EVs serve multiple critical biologic functions, including cellular remodeling, intracellular communication, modulation of the tumor microenvironment and regulation of immune function. Because EVs contain genetic and proteomic contents that reflect the cell of origin, it is possible to detect tumor-specific material in EVs secreted by cancer cells. Importantly, EVs secreted by cancer cells transgress anatomic compartments and can be detected in the blood, cerebrospinal fluid, and other biofluids of cancer patients. In this context, there is a growing interest in analyzing EVs from the biofluid of cancer patients as a means of disease diagnosis and therapeutic monitoring. In this article, we review the development of EVs as a diagnostic platform for the most common form of brain cancer, glioblastoma, discuss potential clinical translational opportunities and identify the central challenges associated with future clinical applications.
Between 2005 and 2010, we treated patients with hydrocephalus related to cerebral metastases, who... more Between 2005 and 2010, we treated patients with hydrocephalus related to cerebral metastases, who were not good candidates for surgical resection by either endoscopic third ventriculostomy (ETV) or ventriculoperitoneal shunting (VPS). Patients were excluded from ETV if they had a clinical history suggestive of non-obstructive hydrocephalus, including: (1) history of infection or ventricular hemorrhage and (2) leptomeningeal carcinomatosis. The rest of the patients were treated with VPS. We analyzed the clinical outcome of these patient cohorts, to determine whether the efficacy of VPS was compromised due to a history of infection, ventricular hemorrhage, or leptomeningeal carcinomatosis, and compared these results to those patients who underwent ETV. Sixteen patients were treated with ETV and 36 patients were treated with VPS. The overall efficacy of symptomatic palliation was comparable in the ETV and VPS patients (ETV = 69%, VPS = 75%). In both groups, patients with more severe hydrocephalic symptoms such as nausea, vomiting, and lethargy were more likely to benefit from the procedure. The overall complication rate for the two groups was comparable (ETV = 12.6%, VPS = 19.4%), although the spectrum of complications differed. The overall survival, initial Karnofsky performance status (KPS), and three-month KPS, were similarly comparable (median survival: ETV 3 months, VPS 5.5 months; initial KPS: ETV = 66 ± 7, VPS = 69 ± 12; 3 months KPS: ETV = 86 ± 7, KPS = 84 ± 12). VPS remains a reasonable option for poor RPA grade metastasis patients with hydrocephalus, even in the setting of a previous infection, hemorrhage, or in those with leptomeningeal disease. Optimal treatment of this population will involve the judicious consideration of the relative merits of VPS and ETV.
The ubiquitin-dependent degradation of a test protein beta-galactosidase (beta gal) is preceded b... more The ubiquitin-dependent degradation of a test protein beta-galactosidase (beta gal) is preceded by ubiquitination of beta gal. The many (from 1 to more than 20) ubiquitin moieties attached to a molecule of beta gal occur as an ordered chain of branched ubiquitin-ubiquitin conjugates in which the carboxyl-terminal Gly76 of one ubiquitin is jointed to the internal Lys48 of an adjacent ubiquitin. This multiubiquitin chain is linked to one of two specific Lys residues in beta gal. These same Lys residues have been identified by molecular genetic analysis as components of the aminoterminal degradation signal in beta gal. The experiments with ubiquitin mutated at its Lys48 residue indicate that the multiubiquitin chain in a targeted protein is essential for the degradation of the protein.
ABSTRACT INTRODUCTION: Object: To overcome the temporal and spacial limitations of classical subc... more ABSTRACT INTRODUCTION: Object: To overcome the temporal and spacial limitations of classical subcortical mapping of the corticospinal tract. We evaluated the feasibility and safety of continuous and dynamic subcortical motor mapping especially at low motor thresholds. METHODS: We prospectively studied 69 patients who underwent tumor surgery adjacent to the CST with simultaneous subcortical monopolar motor mapping. Continuous (temporal coverage) and dynamic (spacial coverage) mapping was technically realized by integrating the mapping probe at the tip of a new suction device with the concept that this device will be in contact with the tissue where the resection is performed. Motor function was assessed 1 day after surgery, at discharge, and at 3 months. RESULTS: The initial evaluation in 24 patients showed a 1:1 correlation of MTs for stimulation sites simultaneously mapped with the new suction mapping device and the classic fingerstick probe (74 stimulation points, r = 0.996, P < .001). Thereafter, the fingerstick probe was no longer used and mapping was performed only using the continuous dynamic technique. All procedures were technically successful. Lowest individual motor thresholds (MTs) were as follows (MT, number of patients): >20 mA, n = 7; 11-20 mA, n = 13; 6-10 mA, n = 8; 4-5 mA, n = 17; 1-3 mA, n = 24. At 3 months, 2 patients had a persisting postoperative motor deficit (3%), both were caused by a vascular injury. There was no permanent motor deficit caused by a mechanical injury of the CST. CONCLUSION: Continuous dynamic mapping was found to be a feasible and ergonomic technique of localizing the exact site and distance to the CST. The acoustic feedback and the ability to continuously stimulate the tissue exactly at the site of tissue removal improves the accuracy of mapping especially at low (<5 mA) stimulation intensities. This new technique may increase the safety of motor eloquent tumor surgery. Copyright (C) by the Congress of Neurological Surgeons
Hospital readmission within 30 days of discharge is a major contributor to the high cost of healt... more Hospital readmission within 30 days of discharge is a major contributor to the high cost of health care in the US and is also a major indicator of patient care quality. The purpose of this study was to investigate the incidence, causes, and predictors of 30-day readmission following craniotomy for malignant supratentorial tumor resection. The longitudinal California Office of Statewide Health Planning & Development inpatient-discharge administrative database is a data set that consists of 100% of all inpatient hospitalizations within the state of California and allows each patient to be followed throughout multiple inpatient hospital stays, across multiple institutions, and over multiple years (from 1995 to 2010). This database was used to identify patients who underwent a craniotomy for resection of primary malignant brain tumors. Causes for unplanned 30-day readmission were identified by principle ICD-9 diagnosis code and multivariate analysis was used to determine the independent effect of various patient factors on 30-day readmissions. A total of 18,506 patients received a craniotomy for the treatment of primary malignant brain tumors within the state of California between 1995 and 2010. Four hundred ten patients (2.2%) died during the index surgical admission, 13,586 patients (73.4%) were discharged home, and 4510 patients (24.4%) were transferred to another facility. Among patients discharged home, 1790 patients (13.2%) were readmitted at least once within 30 days of discharge, with 27% of readmissions occurring at a different hospital than the initial surgical institution. The most common reasons for readmission were new onset seizure and convulsive disorder (20.9%), surgical infection of the CNS (14.5%), and new onset of a motor deficit (12.8%). Medi-Cal beneficiaries were at increased odds for readmission relative to privately insured patients (OR 1.52, 95% CI 1.20-1.93). Patients with a history of prior myocardial infarction were at an increased risk of readmission (OR 1.64, 95% CI 1.06-2.54) as were patients who developed hydrocephalus (OR 1.58, 95% CI 1.20-2.07) or venous complications during index surgical admission (OR 3.88, 95% CI 1.84-8.18). Using administrative data, this study demonstrates a baseline glioma surgery 30-day readmission rate of 13.2% in California for patients who are initially discharged home. This paper highlights the medical histories, perioperative complications, and patient demographic groups that are at an increased risk for readmission within 30 days of home discharge. An analysis of conditions present on readmission that were not present at the index surgical admission, such as infection and seizures, suggests that some readmissions may be preventable. Discharge planning strategies aimed at reducing readmission rates in neurosurgical practice should focus on patient groups at high risk for readmission and comprehensive discharge planning protocols should be implemented to specifically target the mitigation of potentially preventable conditions that are highly associated with readmission.
Glioma is the most common brain tumor. For the more aggressive form, glioblastoma, standard treat... more Glioma is the most common brain tumor. For the more aggressive form, glioblastoma, standard treatment includes surgical resection, irradiation with adjuvant temozolomide and, on recurrence, experimental chemotherapy. However, the survival of patients remains poor. There is a critical need for minimally invasive biomarkers for diagnosis and as measures of response to therapeutic interventions. Glioma shed extracellular vesicles (EVs), which invade the surrounding tissue and circulate within both the cerebrospinal fluid and the systemic circulation. These tumor-derived EVs and their content serve as an attractive source of biomarkers. In this review, we discuss the current state of the art of biomarkers for glioma with emphasis on their EV derivation.
Craniofacial procedures may be needed to address symptomatic intracranial hypertension. The autho... more Craniofacial procedures may be needed to address symptomatic intracranial hypertension. The authors review their institutional experience in the treatment of children with symptomatic increased intracranial pressure (ICP) utilizing craniofacial reconstructive procedures. The senior authors' (HSM, SRC) craniofacial experience of 222 patients over a 7-year period from 2000 to 2007 at a single institution (Rady Children's Hospital, San Diego) is reviewed. Seventeen patients were identified who were felt to be candidates for craniofacial surgery with symptomatic increased ICP. Patient diagnoses included single-suture craniosynostosis, craniofacial dysostoses, shunt-induced craniostenosis, and shunt-associated intracranial hypertension (slit-ventricle syndrome). Seventeen patients underwent 21 craniofacial procedures. Age at surgery ranged from 3 months to 13 years with a mean of 5 years. Preoperative symptoms and signs included headaches, unexplained irritability, seizures, papilledema, and visual loss. All patients had diagnostic neuroimaging. Seven patients had preoperative invasive ICP measurements. Surgery was deferred on three of these patients based on these measurements. The mean total operative (including anesthetic preparation) and surgical times were 3 h 12 min and 2 h 20 min, respectively. Percentage operative blood loss averaged 11.3%. In six procedures, no transfusions were required. Average hospital stay was 4 days. There was no perioperative mortality or significant surgery associated morbidity. All patients have had postoperative clinical improvement in signs and symptoms of increased ICP. Using modern diagnostic and surgical techniques, including invasive ICP monitoring, increased intracranial pressure can be successfully managed by an experienced, multidisciplinary, craniofacial team. Our treatment paradigm and operative management scheme is discussed.
Uploads