OBJECTIVE The comparative effectiveness of the 2 treatment options-surgical clipping and endovasc... more OBJECTIVE The comparative effectiveness of the 2 treatment options-surgical clipping and endovascular coiling-for unruptured cerebral aneurysms remains an issue of debate and has not been studied in clinical trials. The authors investigated the association between treatment method for unruptured cerebral aneurysms and outcomes in elderly patients. METHODS The authors performed a cohort study of 100% of Medicare fee-for-service claims data for elderly patients who had treatment for unruptured cerebral aneurysms between 2007 and 2012. To control for measured confounding, the authors used propensity score conditioning and inverse probability weighting with mixed effects to account for clustering at the level of the hospital referral region (HRR). An instrumental variable (regional rates of coiling) analysis was used to control for unmeasured confounding and to create pseudo-randomization on the treatment method. RESULTS During the study period, 8705 patients underwent treatment for unr...
Journal of neurointerventional surgery, Jan 24, 2016
The cost difference between the two treatment options (surgical clipping and endovascular therapy... more The cost difference between the two treatment options (surgical clipping and endovascular therapy) for unruptured cerebral aneurysms remains an issue of debate. We investigated the association between treatment method for unruptured cerebral aneurysms and Medicare expenditures in elderly patients. We performed a cohort study of 100% Medicare fee-for-service claims data for elderly patients who underwent treatment for unruptured cerebral aneurysms from 2007 to 2012. In order to control for measured confounding we used multivariable regression analysis with mixed effects to account for clustering at the Hospital Referral Region (HRR) level. An instrumental variable (regional rates of endovascular treatment) analysis was used to control for unmeasured confounding by creating pseudo-randomization on the treatment method. During the study period 8705 patients underwent treatment for unruptured cerebral aneurysms and met the inclusion criteria. Of these, 2585 (29.7%) had surgical clipping...
Background and purpose: Mutation of arteriovenous malformation (AVM) causal genes in the endothel... more Background and purpose: Mutation of arteriovenous malformation (AVM) causal genes in the endothelial cells (ECs) is essential for AVM formation. However, the relationship of the mutant EC-dose and AVM severity is not clear. We tested whether reduction of mutant ECs reduces bAVM severity using three mouse models that mimic human hereditary hemorrhagic telangiectasia (HHT), a familiar form of bAVM. Majority of HHT patients have Alk1 or endoglin ( Eng ) gene mutation. Methods: Model 1 is Pdgfb iCreER; Alk1 2f/2f mouse that expresses an EC-specific estrogen inducible cre recombinase and has its Alk1 gene exon 4-6 floxed. Alk1 gene deletion was induced by treating the mice with different doses of tamoxifen (TM, 1.25, 0.75, or 0.01 mg/25g of body weight). Model 2 is RosaCreER; Eng 2f/2f mouse that expresses a estrogen inducible cre globally and has exon 5 and 6 of its Eng gene floxed. Model 3 is Pdgfb iCreER; Eng 2f/2f mice. The EC Eng deletion in Model 2 & 3 was induced by three doses of TM (TM 2.5M/25g) treatment. The icre in Pdgfb iCreER transgene has a codon mutant, which is more efficient in deletion of floxed alleles than wild-type cre. BAVMs were induced in TM treated mice through intra-brain injection of AAV-VEGF. Gene deletion efficiency was quantified by qPCR and immunostaining. BAVM phenotypes were analyzed histologically. Results: In model 1, reduction of TM dose reduces the number of Alk1 null ECs and the severity of bAVM. The number of abnormal vessels in bAVM is positively correlated with the TM doses (R=0.8) and negatively correlated with Alk1 positive ECs (R=-0.9). Reduction of TM has also reduced mouse mortality. Compared to Rosa-CreER-mediated global Eng deletion, pdgfb- icreER-induced EC Eng deletion did not increase the number of abnormal vessels, but reduced vascular mural cell-coverage and increased hemorrhage in the bAVM lesion. Conclusion: Reduction of mutant ECs reduces bAVM severity.
OBJECTIVE Disposable supplies constitute a large portion of operating room (OR) costs and are oft... more OBJECTIVE Disposable supplies constitute a large portion of operating room (OR) costs and are often left over at the end of a surgical case. Despite financial and environmental implications of such waste, there has been little evaluation of OR supply utilization. The goal of this study was to quantify the utilization of disposable supplies and the costs associated with opened but unused items (i.e., "waste") in neurosurgical procedures. METHODS Every disposable supply that was unused at the end of surgery was quantified through direct observation of 58 neurosurgical cases at the University of California, San Francisco, in August 2015. Item costs (in US dollars) were determined from the authors' supply catalog, and statistical analyses were performed. RESULTS Across 58 procedures (36 cranial, 22 spinal), the average cost of unused supplies was $653 (range $89-$3640, median $448, interquartile range $230-$810), or 13.1% of total surgical supply cost. Univariate analyses ...
An updated species list on the herpetofauna of Siquijor Island is presented and briefly annotated... more An updated species list on the herpetofauna of Siquijor Island is presented and briefly annotated. Gekko mindorensis, Fejervarya cancrivora, and Cuora amboinensis are new additions to the island's herpetofauna. The zoogeography of Siquijor is briefly discussed. Due to certain morphological variations of the Gekko mindorensis, Lamprolepis smaragdina, and Draco spilopterus populations in Siquijor, further studies should be conducted, including the taxonomic re-evaluation of these species and on the subject of their biogeography.
A variety of pathogenic mechanisms have been described in the formation, maturation, and rupture ... more A variety of pathogenic mechanisms have been described in the formation, maturation, and rupture of brain arteriovenous malformations (bAVMs). While the understanding of bAVMs has largely been formulated based on animal models of rare hereditary diseases in which AVMs form, a new era of “omics” has permitted large-scale examinations of contributory genetic variations in human sporadic bAVMs. New findings regarding the pathogenesis of bAVMs implicate changes to endothelial and mural cells that result in increased angiogenesis, proinflammatory recruitment, and breakdown of vascular barrier properties that may result in hemorrhage; a greater diversity of cell populations that compose the bAVM microenvironment may also be implicated and complicate traditional models. Genomic sequencing of human bAVMs has uncovered inherited, de novo, and somatic activating mutations, such as KRAS, which contribute to the pathogenesis of bAVMs. New droplet-based, single-cell sequencing technologies have ...
Journal of Neurology, Neurosurgery & Psychiatry, 2015
ObjectiveTo delineate treatment and quality of life of non-motor symptoms (NMS) in early Parkinso... more ObjectiveTo delineate treatment and quality of life of non-motor symptoms (NMS) in early Parkinson's disease (PD) and first-degree relatives.BackgroundNon-motor symptoms (NMS) are an important prodromal feature of Parkinson's disease (PD). However, their frequency, treatment rates and impact on health-related quality of life (HRQoL) in the early motor phase is unclear.Methods769 population-ascertained PD subjects within 3.5 years of diagnosis and 287 control subjects were assessed. Validated severity questionnaires were employed to assess NMS symptoms across the following domains: (1) neuropsychiatric (2) gastrointestinal (3) sleep (4) sensory (5) autonomic (6) sexual. Health related quality of life (HRQoL), functional status and management were also evaluated.ResultsNMS were common in early PD. More than half of the PD cases had hyposmia, pain, fatigue, sleep disturbance or urinary dysfunction. PD cases had worse HRQoL scores than controls (OR 4.1, p<0.001) with depressi...
Patients with bilateral, multiple intracranial aneurysms (IA) can be safely treated using one lat... more Patients with bilateral, multiple intracranial aneurysms (IA) can be safely treated using one lateral craniotomy. However, in patients with an additional PcaA or distal ACA aneurysm, an interhemispheric approach through a bifrontal craniotomy is needed. Here, we investigate the safety of a single incision with dual ipsilateral craniotomies (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;squeeze play&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;) and compare results to two separate staged surgeries. Retrospective data collection and analysis of all patients with multiple IAs including a PcaA or complex ACA aneurysm between 1997 and 2016. Univariate statistical analysis was performed to compare radiological and clinical outcomes. Both the squeeze play (n=12) and control group (n=16) showed similar female gender and mean age distribution with a higher mean aneurysm number in the squeeze play group. Indication for surgery was mainly SAH for the control group (12/16). Mean aneurysm diameter of the largest aneurysm treated with the lateral craniotomy was higher in the squeeze play group (15.8 vs 4.7mm, p=0.005) with comparable craniotomy types between both groups. Cumulative EBL was higher in the control group with a comparable cumulative OR time, reoperation rate and favorable clinical outcome in both groups. Single-staged surgery with a single incision and dual ipsilateral craniotomies is a safe treatment for multiple unruptured aneurysms that include PcaA and distal ACA aneurysms. The squeeze play results in clinical and radiological outcomes comparable to a two-staged control group. In the setting of SAH, two-staged surgery with a recovery interval is preferred to prevent bilateral manipulation of the acutely injured brain.
Journal of neurological surgery. Part A, Central European neurosurgery, 2013
Anterior surgical approaches to the inferior frontal lobe require large craniotomies with long in... more Anterior surgical approaches to the inferior frontal lobe require large craniotomies with long incisions and some risk of cosmetic defects and surgical morbidity. A mini supraorbital keyhole approach is an alternative to these larger craniotomies. Inferior frontal lobe cavernous malformations are an excellent target for this minimally invasive approach, and we present our experience with two patients. Two patients with inferior frontal lobe cavernous malformations underwent elective resection of their cavernous malformations through a mini supraorbital craniotomy. The subfrontal exposure opened widely after draining cerebrospinal fluid (CSF) from the carotid cistern to relax the brain. Hemosiderin staining helped identify the underlying cavernous malformations. Both lesions were completely resected. No intraoperative complications, CSF leaks, or neurological deficits were observed. The mini supraorbital keyhole craniotomy with microsurgical technique and neuronavigation is an effect...
Safe, effective treatment of brain arteriovenous malformations (AVMs) remains a challenge despite... more Safe, effective treatment of brain arteriovenous malformations (AVMs) remains a challenge despite advances in endovascular technology, surgical technique, and stereotactic radiosurgery. Patients typically present between 20 and 40 years of age with hemorrhage, seizures, neurological deficits, or headaches (8). AVMs have an annual hemorrhage rate of 1 to 4% and a rehemorrhage rate of 6 to 18% in the year after hemorrhage, returning thereafter to an annual hemorrhage rate of 1 to 4%. The morbidity and mortality rates associated with AVM rupture are as high as 53 to 81% and 10 to 18%, respectively (8, 13, 21, 32). In light of these hemorrhage risks, the treatment of AVMs is an important priority for cerebrovascular specialists, with the goal of resecting or obliterating the nidus with acceptably low therapeutic risk, and thereby avoiding neurological deficits or deaths that accompany hemorrhage. Other less threatening symptoms, such as seizures, progressive neurological deficits, and headaches may also warrant consideration for treatment.
OBJECTIVE The comparative effectiveness of the 2 treatment options-surgical clipping and endovasc... more OBJECTIVE The comparative effectiveness of the 2 treatment options-surgical clipping and endovascular coiling-for unruptured cerebral aneurysms remains an issue of debate and has not been studied in clinical trials. The authors investigated the association between treatment method for unruptured cerebral aneurysms and outcomes in elderly patients. METHODS The authors performed a cohort study of 100% of Medicare fee-for-service claims data for elderly patients who had treatment for unruptured cerebral aneurysms between 2007 and 2012. To control for measured confounding, the authors used propensity score conditioning and inverse probability weighting with mixed effects to account for clustering at the level of the hospital referral region (HRR). An instrumental variable (regional rates of coiling) analysis was used to control for unmeasured confounding and to create pseudo-randomization on the treatment method. RESULTS During the study period, 8705 patients underwent treatment for unr...
Journal of neurointerventional surgery, Jan 24, 2016
The cost difference between the two treatment options (surgical clipping and endovascular therapy... more The cost difference between the two treatment options (surgical clipping and endovascular therapy) for unruptured cerebral aneurysms remains an issue of debate. We investigated the association between treatment method for unruptured cerebral aneurysms and Medicare expenditures in elderly patients. We performed a cohort study of 100% Medicare fee-for-service claims data for elderly patients who underwent treatment for unruptured cerebral aneurysms from 2007 to 2012. In order to control for measured confounding we used multivariable regression analysis with mixed effects to account for clustering at the Hospital Referral Region (HRR) level. An instrumental variable (regional rates of endovascular treatment) analysis was used to control for unmeasured confounding by creating pseudo-randomization on the treatment method. During the study period 8705 patients underwent treatment for unruptured cerebral aneurysms and met the inclusion criteria. Of these, 2585 (29.7%) had surgical clipping...
Background and purpose: Mutation of arteriovenous malformation (AVM) causal genes in the endothel... more Background and purpose: Mutation of arteriovenous malformation (AVM) causal genes in the endothelial cells (ECs) is essential for AVM formation. However, the relationship of the mutant EC-dose and AVM severity is not clear. We tested whether reduction of mutant ECs reduces bAVM severity using three mouse models that mimic human hereditary hemorrhagic telangiectasia (HHT), a familiar form of bAVM. Majority of HHT patients have Alk1 or endoglin ( Eng ) gene mutation. Methods: Model 1 is Pdgfb iCreER; Alk1 2f/2f mouse that expresses an EC-specific estrogen inducible cre recombinase and has its Alk1 gene exon 4-6 floxed. Alk1 gene deletion was induced by treating the mice with different doses of tamoxifen (TM, 1.25, 0.75, or 0.01 mg/25g of body weight). Model 2 is RosaCreER; Eng 2f/2f mouse that expresses a estrogen inducible cre globally and has exon 5 and 6 of its Eng gene floxed. Model 3 is Pdgfb iCreER; Eng 2f/2f mice. The EC Eng deletion in Model 2 &amp;amp;amp; 3 was induced by three doses of TM (TM 2.5M/25g) treatment. The icre in Pdgfb iCreER transgene has a codon mutant, which is more efficient in deletion of floxed alleles than wild-type cre. BAVMs were induced in TM treated mice through intra-brain injection of AAV-VEGF. Gene deletion efficiency was quantified by qPCR and immunostaining. BAVM phenotypes were analyzed histologically. Results: In model 1, reduction of TM dose reduces the number of Alk1 null ECs and the severity of bAVM. The number of abnormal vessels in bAVM is positively correlated with the TM doses (R=0.8) and negatively correlated with Alk1 positive ECs (R=-0.9). Reduction of TM has also reduced mouse mortality. Compared to Rosa-CreER-mediated global Eng deletion, pdgfb- icreER-induced EC Eng deletion did not increase the number of abnormal vessels, but reduced vascular mural cell-coverage and increased hemorrhage in the bAVM lesion. Conclusion: Reduction of mutant ECs reduces bAVM severity.
OBJECTIVE Disposable supplies constitute a large portion of operating room (OR) costs and are oft... more OBJECTIVE Disposable supplies constitute a large portion of operating room (OR) costs and are often left over at the end of a surgical case. Despite financial and environmental implications of such waste, there has been little evaluation of OR supply utilization. The goal of this study was to quantify the utilization of disposable supplies and the costs associated with opened but unused items (i.e., "waste") in neurosurgical procedures. METHODS Every disposable supply that was unused at the end of surgery was quantified through direct observation of 58 neurosurgical cases at the University of California, San Francisco, in August 2015. Item costs (in US dollars) were determined from the authors' supply catalog, and statistical analyses were performed. RESULTS Across 58 procedures (36 cranial, 22 spinal), the average cost of unused supplies was $653 (range $89-$3640, median $448, interquartile range $230-$810), or 13.1% of total surgical supply cost. Univariate analyses ...
An updated species list on the herpetofauna of Siquijor Island is presented and briefly annotated... more An updated species list on the herpetofauna of Siquijor Island is presented and briefly annotated. Gekko mindorensis, Fejervarya cancrivora, and Cuora amboinensis are new additions to the island's herpetofauna. The zoogeography of Siquijor is briefly discussed. Due to certain morphological variations of the Gekko mindorensis, Lamprolepis smaragdina, and Draco spilopterus populations in Siquijor, further studies should be conducted, including the taxonomic re-evaluation of these species and on the subject of their biogeography.
A variety of pathogenic mechanisms have been described in the formation, maturation, and rupture ... more A variety of pathogenic mechanisms have been described in the formation, maturation, and rupture of brain arteriovenous malformations (bAVMs). While the understanding of bAVMs has largely been formulated based on animal models of rare hereditary diseases in which AVMs form, a new era of “omics” has permitted large-scale examinations of contributory genetic variations in human sporadic bAVMs. New findings regarding the pathogenesis of bAVMs implicate changes to endothelial and mural cells that result in increased angiogenesis, proinflammatory recruitment, and breakdown of vascular barrier properties that may result in hemorrhage; a greater diversity of cell populations that compose the bAVM microenvironment may also be implicated and complicate traditional models. Genomic sequencing of human bAVMs has uncovered inherited, de novo, and somatic activating mutations, such as KRAS, which contribute to the pathogenesis of bAVMs. New droplet-based, single-cell sequencing technologies have ...
Journal of Neurology, Neurosurgery & Psychiatry, 2015
ObjectiveTo delineate treatment and quality of life of non-motor symptoms (NMS) in early Parkinso... more ObjectiveTo delineate treatment and quality of life of non-motor symptoms (NMS) in early Parkinson's disease (PD) and first-degree relatives.BackgroundNon-motor symptoms (NMS) are an important prodromal feature of Parkinson's disease (PD). However, their frequency, treatment rates and impact on health-related quality of life (HRQoL) in the early motor phase is unclear.Methods769 population-ascertained PD subjects within 3.5 years of diagnosis and 287 control subjects were assessed. Validated severity questionnaires were employed to assess NMS symptoms across the following domains: (1) neuropsychiatric (2) gastrointestinal (3) sleep (4) sensory (5) autonomic (6) sexual. Health related quality of life (HRQoL), functional status and management were also evaluated.ResultsNMS were common in early PD. More than half of the PD cases had hyposmia, pain, fatigue, sleep disturbance or urinary dysfunction. PD cases had worse HRQoL scores than controls (OR 4.1, p<0.001) with depressi...
Patients with bilateral, multiple intracranial aneurysms (IA) can be safely treated using one lat... more Patients with bilateral, multiple intracranial aneurysms (IA) can be safely treated using one lateral craniotomy. However, in patients with an additional PcaA or distal ACA aneurysm, an interhemispheric approach through a bifrontal craniotomy is needed. Here, we investigate the safety of a single incision with dual ipsilateral craniotomies (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;squeeze play&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;) and compare results to two separate staged surgeries. Retrospective data collection and analysis of all patients with multiple IAs including a PcaA or complex ACA aneurysm between 1997 and 2016. Univariate statistical analysis was performed to compare radiological and clinical outcomes. Both the squeeze play (n=12) and control group (n=16) showed similar female gender and mean age distribution with a higher mean aneurysm number in the squeeze play group. Indication for surgery was mainly SAH for the control group (12/16). Mean aneurysm diameter of the largest aneurysm treated with the lateral craniotomy was higher in the squeeze play group (15.8 vs 4.7mm, p=0.005) with comparable craniotomy types between both groups. Cumulative EBL was higher in the control group with a comparable cumulative OR time, reoperation rate and favorable clinical outcome in both groups. Single-staged surgery with a single incision and dual ipsilateral craniotomies is a safe treatment for multiple unruptured aneurysms that include PcaA and distal ACA aneurysms. The squeeze play results in clinical and radiological outcomes comparable to a two-staged control group. In the setting of SAH, two-staged surgery with a recovery interval is preferred to prevent bilateral manipulation of the acutely injured brain.
Journal of neurological surgery. Part A, Central European neurosurgery, 2013
Anterior surgical approaches to the inferior frontal lobe require large craniotomies with long in... more Anterior surgical approaches to the inferior frontal lobe require large craniotomies with long incisions and some risk of cosmetic defects and surgical morbidity. A mini supraorbital keyhole approach is an alternative to these larger craniotomies. Inferior frontal lobe cavernous malformations are an excellent target for this minimally invasive approach, and we present our experience with two patients. Two patients with inferior frontal lobe cavernous malformations underwent elective resection of their cavernous malformations through a mini supraorbital craniotomy. The subfrontal exposure opened widely after draining cerebrospinal fluid (CSF) from the carotid cistern to relax the brain. Hemosiderin staining helped identify the underlying cavernous malformations. Both lesions were completely resected. No intraoperative complications, CSF leaks, or neurological deficits were observed. The mini supraorbital keyhole craniotomy with microsurgical technique and neuronavigation is an effect...
Safe, effective treatment of brain arteriovenous malformations (AVMs) remains a challenge despite... more Safe, effective treatment of brain arteriovenous malformations (AVMs) remains a challenge despite advances in endovascular technology, surgical technique, and stereotactic radiosurgery. Patients typically present between 20 and 40 years of age with hemorrhage, seizures, neurological deficits, or headaches (8). AVMs have an annual hemorrhage rate of 1 to 4% and a rehemorrhage rate of 6 to 18% in the year after hemorrhage, returning thereafter to an annual hemorrhage rate of 1 to 4%. The morbidity and mortality rates associated with AVM rupture are as high as 53 to 81% and 10 to 18%, respectively (8, 13, 21, 32). In light of these hemorrhage risks, the treatment of AVMs is an important priority for cerebrovascular specialists, with the goal of resecting or obliterating the nidus with acceptably low therapeutic risk, and thereby avoiding neurological deficits or deaths that accompany hemorrhage. Other less threatening symptoms, such as seizures, progressive neurological deficits, and headaches may also warrant consideration for treatment.
Uploads
Papers by Dr. Michael Lawton