Mohammad Faizan Khan, A. Conching, Lane Fry, Dillon Putzer, Ammar Haider, Ali S. Haider, G. Ferini, Mayur Sharma, G. Umana, Paolo Palmisciano, Gina Watanabe
Background: Intraventricular neoplasms are rare occurrences observed in 5 – 7% of all primary pediatric brain tumors. Pediatric intraventricular ependymomas are a complex subset of these tumors, poorly discussed across the current literature. Although surgery is generally the accepted treatment of choice, information on clinical course and outcomes is limited to heterogeneous case reports and small case series focusing on specific histologic subtypes or ventricular locations. We conducted a systematic review on pediatric intraventricular ependymomas to survey the patient population, tumor characteristics, management strategies, and associated outcomes. Project Methods: PubMed, Scopus, Web-of-Science, and Cochrane were searched upon the PRISMA guidelines to include studies reporting pediatric patients with intraventricular ependymomas. Clinical characteristics, treatment protocols, and outcomes were analyzed. Results: A total of 9 studies with 70 patients were included. Most patients were male (54%), diagnosed at a mean age of 7 years (range, 0.2-17), and frequently exhibited nausea and vomiting (38%), headache (31%), and ataxia (25%). Tumors were predominantly located in the fourth ventricle (79%) and most tumors were WHO grade 2 (73%). Mean tumor volume was 3 cm3 (range, 0.1-13.2). Management included surgical resection (96%), radiotherapy (87%), and chemotherapy (38%). Gross total resection was achieved in 69% of cases. Cranial nerve deficit was the most common post-surgical complication (71%). Most common combination of treatment included surgical resection and radiotherapy (53%). Mean overall survival was 50 months in these patients. Conclusion/Impact: Pediatric intraventricular ependymomas are rare tumors with limited information on management strategies. The mainstay of treatment is complete surgical resection. Compared to ependymomas, intraventricular ependymomas appear to have a worse overall prognosis.
{"title":"Intraventricular Ependymoma in Pediatric Patients: A Systematic Review of Demographics, Clinical Characteristics, and Outcomes","authors":"Mohammad Faizan Khan, A. Conching, Lane Fry, Dillon Putzer, Ammar Haider, Ali S. Haider, G. Ferini, Mayur Sharma, G. Umana, Paolo Palmisciano, Gina Watanabe","doi":"10.18060/28051","DOIUrl":"https://doi.org/10.18060/28051","url":null,"abstract":"Background: Intraventricular neoplasms are rare occurrences observed in 5 – 7% of all primary pediatric brain tumors. Pediatric intraventricular ependymomas are a complex subset of these tumors, poorly discussed across the current literature. Although surgery is generally the accepted treatment of choice, information on clinical course and outcomes is limited to heterogeneous case reports and small case series focusing on specific histologic subtypes or ventricular locations. We conducted a systematic review on pediatric intraventricular ependymomas to survey the patient population, tumor characteristics, management strategies, and associated outcomes. \u0000Project Methods: PubMed, Scopus, Web-of-Science, and Cochrane were searched upon the PRISMA guidelines to include studies reporting pediatric patients with intraventricular ependymomas. Clinical characteristics, treatment protocols, and outcomes were analyzed. \u0000Results: A total of 9 studies with 70 patients were included. Most patients were male (54%), diagnosed at a mean age of 7 years (range, 0.2-17), and frequently exhibited nausea and vomiting (38%), headache (31%), and ataxia (25%). Tumors were predominantly located in the fourth ventricle (79%) and most tumors were WHO grade 2 (73%). Mean tumor volume was 3 cm3 (range, 0.1-13.2). Management included surgical resection (96%), radiotherapy (87%), and chemotherapy (38%). Gross total resection was achieved in 69% of cases. Cranial nerve deficit was the most common post-surgical complication (71%). Most common combination of treatment included surgical resection and radiotherapy (53%). Mean overall survival was 50 months in these patients. \u0000Conclusion/Impact: Pediatric intraventricular ependymomas are rare tumors with limited information on management strategies. The mainstay of treatment is complete surgical resection. Compared to ependymomas, intraventricular ependymomas appear to have a worse overall prognosis.","PeriodicalId":20522,"journal":{"name":"Proceedings of IMPRS","volume":"9 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139780564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohammad Faizan Khan, Kurtis Young, Erin Rauber, Christian T. Ogasawara, G. Umana, Paolo Palmisciano, Gina Watanabe
Background: Meningioma is the most common type of intracranial neoplasm, accounting for approximately 40% of all primary brain tumors. Although these tumors are usually benign and slow-growing, extracranial metastasis can occur in less than 1% of cases. Due to the rarity, diagnosis can pose a challenge. In this systematic review, we summarize and analyze patient demographics, clinical characteristics, management strategies, and outcomes of patients with extracranial meningioma metastasis. Project Methods: A systematic review was performed following the (PRISMA) guidelines. PubMed, Ovid EMBASE, Cochrane, Scopus, and Web of Science databases were searched. Clinical characteristics, management, and outcomes were analyzed. Results: A total of 127 studies with 164 patients were included. There were 51% males and mean age of primary tumor diagnosis was 48 years (range, 8-91). Primary tumors were mostly located on the convexity of the brain (52%) and WHO grade 1 (38%) or grade 2 (37%). Histological findings were predominantly atypical (37%). Mean number of intracranial recurrences was 2 (range, 0-7) and occurred in 81% of cases. Average time between primary tumor and the first extracranial metastasis was 103 months (range, 2-450). The top three most common locations of metastases were the lungs (39%), spine (15%), and liver (12%). Most often, there was no change in grade (68%) from the primary tumor to the first metastasis. Gross total resection of the primary tumor was achieved in 76% of cases. Mean survival from primary diagnosis and survival from first metastasis was 118 and 31 months, respectively. Conclusion/Impact: Mechanisms by which extracranial meningioma metastasis occur are still unclear, though do not appear to involve evolution into a more aggressive histologic type in most cases. In a patient with a history of intracranial meningioma recurrence and symptoms of lung, spine, or liver, dysfunction, extracranial meningioma metastasis should be considered within the differential.
{"title":"Extracranial Meningioma Metastasis: A Systematic Review of Clinical Characteristics, Management Strategies, and Outcomes","authors":"Mohammad Faizan Khan, Kurtis Young, Erin Rauber, Christian T. Ogasawara, G. Umana, Paolo Palmisciano, Gina Watanabe","doi":"10.18060/28050","DOIUrl":"https://doi.org/10.18060/28050","url":null,"abstract":"Background: Meningioma is the most common type of intracranial neoplasm, accounting for approximately 40% of all primary brain tumors. Although these tumors are usually benign and slow-growing, extracranial metastasis can occur in less than 1% of cases. Due to the rarity, diagnosis can pose a challenge. In this systematic review, we summarize and analyze patient demographics, clinical characteristics, management strategies, and outcomes of patients with extracranial meningioma metastasis. \u0000Project Methods: A systematic review was performed following the (PRISMA) guidelines. PubMed, Ovid EMBASE, Cochrane, Scopus, and Web of Science databases were searched. Clinical characteristics, management, and outcomes were analyzed. \u0000Results: A total of 127 studies with 164 patients were included. There were 51% males and mean age of primary tumor diagnosis was 48 years (range, 8-91). Primary tumors were mostly located on the convexity of the brain (52%) and WHO grade 1 (38%) or grade 2 (37%). Histological findings were predominantly atypical (37%). Mean number of intracranial recurrences was 2 (range, 0-7) and occurred in 81% of cases. Average time between primary tumor and the first extracranial metastasis was 103 months (range, 2-450). The top three most common locations of metastases were the lungs (39%), spine (15%), and liver (12%). Most often, there was no change in grade (68%) from the primary tumor to the first metastasis. Gross total resection of the primary tumor was achieved in 76% of cases. Mean survival from primary diagnosis and survival from first metastasis was 118 and 31 months, respectively. \u0000Conclusion/Impact: Mechanisms by which extracranial meningioma metastasis occur are still unclear, though do not appear to involve evolution into a more aggressive histologic type in most cases. In a patient with a history of intracranial meningioma recurrence and symptoms of lung, spine, or liver, dysfunction, extracranial meningioma metastasis should be considered within the differential.","PeriodicalId":20522,"journal":{"name":"Proceedings of IMPRS","volume":"35 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139840372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohammad Faizan Khan, Kurtis Young, Erin Rauber, Christian T. Ogasawara, G. Umana, Paolo Palmisciano, Gina Watanabe
Background: Meningioma is the most common type of intracranial neoplasm, accounting for approximately 40% of all primary brain tumors. Although these tumors are usually benign and slow-growing, extracranial metastasis can occur in less than 1% of cases. Due to the rarity, diagnosis can pose a challenge. In this systematic review, we summarize and analyze patient demographics, clinical characteristics, management strategies, and outcomes of patients with extracranial meningioma metastasis. Project Methods: A systematic review was performed following the (PRISMA) guidelines. PubMed, Ovid EMBASE, Cochrane, Scopus, and Web of Science databases were searched. Clinical characteristics, management, and outcomes were analyzed. Results: A total of 127 studies with 164 patients were included. There were 51% males and mean age of primary tumor diagnosis was 48 years (range, 8-91). Primary tumors were mostly located on the convexity of the brain (52%) and WHO grade 1 (38%) or grade 2 (37%). Histological findings were predominantly atypical (37%). Mean number of intracranial recurrences was 2 (range, 0-7) and occurred in 81% of cases. Average time between primary tumor and the first extracranial metastasis was 103 months (range, 2-450). The top three most common locations of metastases were the lungs (39%), spine (15%), and liver (12%). Most often, there was no change in grade (68%) from the primary tumor to the first metastasis. Gross total resection of the primary tumor was achieved in 76% of cases. Mean survival from primary diagnosis and survival from first metastasis was 118 and 31 months, respectively. Conclusion/Impact: Mechanisms by which extracranial meningioma metastasis occur are still unclear, though do not appear to involve evolution into a more aggressive histologic type in most cases. In a patient with a history of intracranial meningioma recurrence and symptoms of lung, spine, or liver, dysfunction, extracranial meningioma metastasis should be considered within the differential.
{"title":"Extracranial Meningioma Metastasis: A Systematic Review of Clinical Characteristics, Management Strategies, and Outcomes","authors":"Mohammad Faizan Khan, Kurtis Young, Erin Rauber, Christian T. Ogasawara, G. Umana, Paolo Palmisciano, Gina Watanabe","doi":"10.18060/28050","DOIUrl":"https://doi.org/10.18060/28050","url":null,"abstract":"Background: Meningioma is the most common type of intracranial neoplasm, accounting for approximately 40% of all primary brain tumors. Although these tumors are usually benign and slow-growing, extracranial metastasis can occur in less than 1% of cases. Due to the rarity, diagnosis can pose a challenge. In this systematic review, we summarize and analyze patient demographics, clinical characteristics, management strategies, and outcomes of patients with extracranial meningioma metastasis. \u0000Project Methods: A systematic review was performed following the (PRISMA) guidelines. PubMed, Ovid EMBASE, Cochrane, Scopus, and Web of Science databases were searched. Clinical characteristics, management, and outcomes were analyzed. \u0000Results: A total of 127 studies with 164 patients were included. There were 51% males and mean age of primary tumor diagnosis was 48 years (range, 8-91). Primary tumors were mostly located on the convexity of the brain (52%) and WHO grade 1 (38%) or grade 2 (37%). Histological findings were predominantly atypical (37%). Mean number of intracranial recurrences was 2 (range, 0-7) and occurred in 81% of cases. Average time between primary tumor and the first extracranial metastasis was 103 months (range, 2-450). The top three most common locations of metastases were the lungs (39%), spine (15%), and liver (12%). Most often, there was no change in grade (68%) from the primary tumor to the first metastasis. Gross total resection of the primary tumor was achieved in 76% of cases. Mean survival from primary diagnosis and survival from first metastasis was 118 and 31 months, respectively. \u0000Conclusion/Impact: Mechanisms by which extracranial meningioma metastasis occur are still unclear, though do not appear to involve evolution into a more aggressive histologic type in most cases. In a patient with a history of intracranial meningioma recurrence and symptoms of lung, spine, or liver, dysfunction, extracranial meningioma metastasis should be considered within the differential.","PeriodicalId":20522,"journal":{"name":"Proceedings of IMPRS","volume":"141 51","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139780517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohammad Faizan Khan, A. Conching, Lane Fry, Dillon Putzer, Ammar Haider, Ali S. Haider, G. Ferini, Mayur Sharma, G. Umana, Paolo Palmisciano, Gina Watanabe
Background: Intraventricular neoplasms are rare occurrences observed in 5 – 7% of all primary pediatric brain tumors. Pediatric intraventricular ependymomas are a complex subset of these tumors, poorly discussed across the current literature. Although surgery is generally the accepted treatment of choice, information on clinical course and outcomes is limited to heterogeneous case reports and small case series focusing on specific histologic subtypes or ventricular locations. We conducted a systematic review on pediatric intraventricular ependymomas to survey the patient population, tumor characteristics, management strategies, and associated outcomes. Project Methods: PubMed, Scopus, Web-of-Science, and Cochrane were searched upon the PRISMA guidelines to include studies reporting pediatric patients with intraventricular ependymomas. Clinical characteristics, treatment protocols, and outcomes were analyzed. Results: A total of 9 studies with 70 patients were included. Most patients were male (54%), diagnosed at a mean age of 7 years (range, 0.2-17), and frequently exhibited nausea and vomiting (38%), headache (31%), and ataxia (25%). Tumors were predominantly located in the fourth ventricle (79%) and most tumors were WHO grade 2 (73%). Mean tumor volume was 3 cm3 (range, 0.1-13.2). Management included surgical resection (96%), radiotherapy (87%), and chemotherapy (38%). Gross total resection was achieved in 69% of cases. Cranial nerve deficit was the most common post-surgical complication (71%). Most common combination of treatment included surgical resection and radiotherapy (53%). Mean overall survival was 50 months in these patients. Conclusion/Impact: Pediatric intraventricular ependymomas are rare tumors with limited information on management strategies. The mainstay of treatment is complete surgical resection. Compared to ependymomas, intraventricular ependymomas appear to have a worse overall prognosis.
{"title":"Intraventricular Ependymoma in Pediatric Patients: A Systematic Review of Demographics, Clinical Characteristics, and Outcomes","authors":"Mohammad Faizan Khan, A. Conching, Lane Fry, Dillon Putzer, Ammar Haider, Ali S. Haider, G. Ferini, Mayur Sharma, G. Umana, Paolo Palmisciano, Gina Watanabe","doi":"10.18060/28051","DOIUrl":"https://doi.org/10.18060/28051","url":null,"abstract":"Background: Intraventricular neoplasms are rare occurrences observed in 5 – 7% of all primary pediatric brain tumors. Pediatric intraventricular ependymomas are a complex subset of these tumors, poorly discussed across the current literature. Although surgery is generally the accepted treatment of choice, information on clinical course and outcomes is limited to heterogeneous case reports and small case series focusing on specific histologic subtypes or ventricular locations. We conducted a systematic review on pediatric intraventricular ependymomas to survey the patient population, tumor characteristics, management strategies, and associated outcomes. \u0000Project Methods: PubMed, Scopus, Web-of-Science, and Cochrane were searched upon the PRISMA guidelines to include studies reporting pediatric patients with intraventricular ependymomas. Clinical characteristics, treatment protocols, and outcomes were analyzed. \u0000Results: A total of 9 studies with 70 patients were included. Most patients were male (54%), diagnosed at a mean age of 7 years (range, 0.2-17), and frequently exhibited nausea and vomiting (38%), headache (31%), and ataxia (25%). Tumors were predominantly located in the fourth ventricle (79%) and most tumors were WHO grade 2 (73%). Mean tumor volume was 3 cm3 (range, 0.1-13.2). Management included surgical resection (96%), radiotherapy (87%), and chemotherapy (38%). Gross total resection was achieved in 69% of cases. Cranial nerve deficit was the most common post-surgical complication (71%). Most common combination of treatment included surgical resection and radiotherapy (53%). Mean overall survival was 50 months in these patients. \u0000Conclusion/Impact: Pediatric intraventricular ependymomas are rare tumors with limited information on management strategies. The mainstay of treatment is complete surgical resection. Compared to ependymomas, intraventricular ependymomas appear to have a worse overall prognosis.","PeriodicalId":20522,"journal":{"name":"Proceedings of IMPRS","volume":"80 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139840321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Kidney stones are a common medical condition that impact approximately 10% of US population. Management of stone disease is based on size and location of stones. Percutaneous nephrolithotomy (PCNL) is typically indicated in patients with large renal stone burden (typically >2 cm) or complex anatomy. In the setting of complex stones, multiple, staged PCNLs are required. We hypothesize that there is no significant difference in the perioperative change in lab values in bilateral PCNLs compared to unilateral PCNLs. Methods: The data was gathered by retrospectively reviewing the electronic medical record of 50 patients in the IU health system who underwent planned staged PCNLs between January and December 2018. We identified patients who underwent both bilateral and unilateral staged procedures. Data for BMI, sex, ethnicity, hemoglobin, estimated glomerular filtration rate (GFR) (typically formula CKD-EPI or MDRD), urine and stone cultures, stone composition, and bilaterality vs. unilaterality was collected. Two-tailed T-tests were performed to analyze data between bilateral and unilateral cases. Results: We identified a total of 50 patients, 19 men vs. 31 women; 9 men and 10 women underwent bilateral PCNLs, while 11 men and 20 women had unilateral PCNLs. BMI ranged from 14.2 to 62.3, and age ranged from 15 to 81. Significant differences were found between the changes in hemoglobin levels in patients who underwent bilateral PCNLs when compared to unilateral PCNLs (p value 0.018). No significant differences were noted when comparing changes of estimated GFR, BMI, age or any other variables. Conclusion: Patients who underwent bilateral staged PCNLs demonstrated a greater drop in perioperative hemoglobin compared to unilateral PCNLs without an increase in blood transfusion. This finding suggests that Bilateral PCNLs requiring multiple stages are safe in complex stone patients.
{"title":"Analysis of Perioperative Events in Bilateral vs Unilateral Staged Percutaneous Nephrolithotomy","authors":"Kyle Edwards, T. Shelton, Marcelino Rivera","doi":"10.18060/27894","DOIUrl":"https://doi.org/10.18060/27894","url":null,"abstract":"Introduction: Kidney stones are a common medical condition that impact approximately 10% of US population. Management of stone disease is based on size and location of stones. Percutaneous nephrolithotomy (PCNL) is typically indicated in patients with large renal stone burden (typically >2 cm) or complex anatomy. In the setting of complex stones, multiple, staged PCNLs are required. We hypothesize that there is no significant difference in the perioperative change in lab values in bilateral PCNLs compared to unilateral PCNLs. \u0000Methods: The data was gathered by retrospectively reviewing the electronic medical record of 50 patients in the IU health system who underwent planned staged PCNLs between January and December 2018. We identified patients who underwent both bilateral and unilateral staged procedures. Data for BMI, sex, ethnicity, hemoglobin, estimated glomerular filtration rate (GFR) (typically formula CKD-EPI or MDRD), urine and stone cultures, stone composition, and bilaterality vs. unilaterality was collected. Two-tailed T-tests were performed to analyze data between bilateral and unilateral cases. \u0000Results: We identified a total of 50 patients, 19 men vs. 31 women; 9 men and 10 women underwent bilateral PCNLs, while 11 men and 20 women had unilateral PCNLs. BMI ranged from 14.2 to 62.3, and age ranged from 15 to 81. Significant differences were found between the changes in hemoglobin levels in patients who underwent bilateral PCNLs when compared to unilateral PCNLs (p value 0.018). No significant differences were noted when comparing changes of estimated GFR, BMI, age or any other variables. \u0000Conclusion: Patients who underwent bilateral staged PCNLs demonstrated a greater drop in perioperative hemoglobin compared to unilateral PCNLs without an increase in blood transfusion. This finding suggests that Bilateral PCNLs requiring multiple stages are safe in complex stone patients.","PeriodicalId":20522,"journal":{"name":"Proceedings of IMPRS","volume":"6 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139438232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Garrett Maag, Hallel C. Paraiso, Hannah Huang, Ivorine Yu
Background and Hypothesis:Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder with undefined etiology and is the fifth leading cause of death worldwide. AD pathology is characterized by amyloid-beta (Aβ) plaques. Previous work demonstrated that alterations in the microvasculature are some of the earliest recognizable changes in AD, and that most patients with dementia have mixed vascular pathologies. We investigated the functional impacts of metabolic disease associated immune-vascular perturbation on the underlying mechanisms of AD. Methods:Adult male Leprdb/J (db/db) were obtained from the Jackson Laboratory. Activated microglia and brain vessel density levels were assessed using immunofluorescence. Cerebral microvessels were isolated for RNA examination using qPCR, and FACS-based analysis of brain endothelial cells. Immunofluorescence of hAβ42 transport in microvessels were observed via confocal microscope. Quantification of images were performed using Fiji (NIH) software. Results:Db/db mice brains displayed higher levels of activated microglia with increased soma area and decreased circularity (p<0.05). This confirms early vascular stress leads to increased immune cell activation. Brain vessel density analysis revealed a non-statistically significant trend with decreased density in db/db mice. Given that functional changes occur before structural changes, we shifted our examination to the microvasculature. Brain microvessels were isolated and validated and both qPCR and FACS results demonstrated increased levels of inflammatory mediators and cell adhesion molecules in db/db mice (p<0.05), confirming microvessel dysfunction and neuroinflammation. Finally, quantification of luminal area fluorescence demonstrated decreased hAβ42 transport in db/db mice (p<0.01), validating functional disturbance in the cerebral microvasculature. Conclusion and Impact:The vascular risk factors of metabolic disease can lead to dysfunction and inflammation in cerebral microvasculature, causing accelerated progression of AD. Our results emphasize the contributory role of cerebral small vessel health in the origin and evolution of AD and present an opportunity for novel development of surrogate biomarkers and therapeutic treatments.
{"title":"Investigating the Functional Impacts of Metabolic Disease Associated Immune-Vascular Interactions in Alzheimer’s Disease","authors":"Garrett Maag, Hallel C. Paraiso, Hannah Huang, Ivorine Yu","doi":"10.18060/27724","DOIUrl":"https://doi.org/10.18060/27724","url":null,"abstract":"Background and Hypothesis:Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder with undefined etiology and is the fifth leading cause of death worldwide. AD pathology is characterized by amyloid-beta (Aβ) plaques. Previous work demonstrated that alterations in the microvasculature are some of the earliest recognizable changes in AD, and that most patients with dementia have mixed vascular pathologies. We investigated the functional impacts of metabolic disease associated immune-vascular perturbation on the underlying mechanisms of AD. \u0000Methods:Adult male Leprdb/J (db/db) were obtained from the Jackson Laboratory. Activated microglia and brain vessel density levels were assessed using immunofluorescence. Cerebral microvessels were isolated for RNA examination using qPCR, and FACS-based analysis of brain endothelial cells. Immunofluorescence of hAβ42 transport in microvessels were observed via confocal microscope. Quantification of images were performed using Fiji (NIH) software. \u0000Results:Db/db mice brains displayed higher levels of activated microglia with increased soma area and decreased circularity (p<0.05). This confirms early vascular stress leads to increased immune cell activation. Brain vessel density analysis revealed a non-statistically significant trend with decreased density in db/db mice. Given that functional changes occur before structural changes, we shifted our examination to the microvasculature. Brain microvessels were isolated and validated and both qPCR and FACS results demonstrated increased levels of inflammatory mediators and cell adhesion molecules in db/db mice (p<0.05), confirming microvessel dysfunction and neuroinflammation. Finally, quantification of luminal area fluorescence demonstrated decreased hAβ42 transport in db/db mice (p<0.01), validating functional disturbance in the cerebral microvasculature. \u0000Conclusion and Impact:The vascular risk factors of metabolic disease can lead to dysfunction and inflammation in cerebral microvasculature, causing accelerated progression of AD. Our results emphasize the contributory role of cerebral small vessel health in the origin and evolution of AD and present an opportunity for novel development of surrogate biomarkers and therapeutic treatments.","PeriodicalId":20522,"journal":{"name":"Proceedings of IMPRS","volume":"10 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139438735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Megan E. Sullivan, Aditya A. Shanghavi, Sarah Elizabeth Zauber, Anne B. Sereno
Background/Objective: Numerous studies have examined motor and cognitive decline in neurodegenerative diseases such as Parkinson’s Disease (PD) and results vary considerably. Studies also show that decline does not occur synchronously across all aspects of cognition or motor functions in PD. The goal was to examine if correlations exist between decline in specific motor and cognitive functions. Experimental Design: A cohort of 15 PD patients (age 49-81;6 female) and 9 healthy controls (age 53-75;4 female) were enrolled and their motor and cognitive functions were assessed. Decline in motor function, covering tremor, rigidity and bradykinesia was evaluated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MS-UPDRS) scores. Cognition, covering attention, memory, language, and visuospatial functions, was assessed using the Montreal Cognitive Assessment (MoCA) test. Inertial measurement units (recording at 100 Hz), placed on both wrists, recorded linear acceleration and angular velocity while subjects performed the pronation/supination and kinetic tremor tasks of the MS-UPDRS. Using angular velocity, response time (RT) to initiate movement in each task was computed. Data analysis correlated MS-UPDRS scores with MoCA scores, and RTs. Results: There were no significant correlations between MS-UPDRS and cognitive MoCA scores. There was a significant relationship between deficits in visuospatial function (MoCA) and increased RT in the pronation/supination task. Conclusion/Potential Impact: Using correlation analyses, no correlation was found between MS-UPDRS and MoCA scores. However, RT on the pronation/supination task correlated positively with visuospatial deficits, suggesting a common voluntary attentional deficit. Although no relationship was found between a clinical score of bradykinesia and RT, measures of movement velocities (measured but not analyzed) may correlate better. Identification of interrelating factors between hard-to-measure cognitive and easy-to-measure motor changes in PD patients may aid clinicians in implementing simple and timely interventions to more easily track and ameliorate cognitive deficits and improve patients' overall functional status.
{"title":"Parkinson’s Disease Progression: Exploring the Relationship between Motor Performance and Cognitive Function","authors":"Megan E. Sullivan, Aditya A. Shanghavi, Sarah Elizabeth Zauber, Anne B. Sereno","doi":"10.18060/27791","DOIUrl":"https://doi.org/10.18060/27791","url":null,"abstract":"Background/Objective: Numerous studies have examined motor and cognitive decline in neurodegenerative diseases such as Parkinson’s Disease (PD) and results vary considerably. Studies also show that decline does not occur synchronously across all aspects of cognition or motor functions in PD. The goal was to examine if correlations exist between decline in specific motor and cognitive functions. \u0000Experimental Design: A cohort of 15 PD patients (age 49-81;6 female) and 9 healthy controls (age 53-75;4 female) were enrolled and their motor and cognitive functions were assessed. Decline in motor function, covering tremor, rigidity and bradykinesia was evaluated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MS-UPDRS) scores. Cognition, covering attention, memory, language, and visuospatial functions, was assessed using the Montreal Cognitive Assessment (MoCA) test. Inertial measurement units (recording at 100 Hz), placed on both wrists, recorded linear acceleration and angular velocity while subjects performed the pronation/supination and kinetic tremor tasks of the MS-UPDRS. Using angular velocity, response time (RT) to initiate movement in each task was computed. Data analysis correlated MS-UPDRS scores with MoCA scores, and RTs. \u0000Results: There were no significant correlations between MS-UPDRS and cognitive MoCA scores. There was a significant relationship between deficits in visuospatial function (MoCA) and increased RT in the pronation/supination task. \u0000Conclusion/Potential Impact: Using correlation analyses, no correlation was found between MS-UPDRS and MoCA scores. However, RT on the pronation/supination task correlated positively with visuospatial deficits, suggesting a common voluntary attentional deficit. Although no relationship was found between a clinical score of bradykinesia and RT, measures of movement velocities (measured but not analyzed) may correlate better. Identification of interrelating factors between hard-to-measure cognitive and easy-to-measure motor changes in PD patients may aid clinicians in implementing simple and timely interventions to more easily track and ameliorate cognitive deficits and improve patients' overall functional status.","PeriodicalId":20522,"journal":{"name":"Proceedings of IMPRS","volume":"40 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139533316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Allyse M. Emmel, Tara S. Umberger, Emma H. Doud, T. Zimmers, Amber L. Mosley
Background and Hypothesis:Cachexia is a wasting syndrome commonly occurring in cancer patients that cannot be explained by decreased calorie intake alone. It results in decreased quality of life and increased mortality, and there are currently no effective treatments. To better understand cachexia, we aimed to profile protein heterogeneity seen in pancreatic ductal adenocarcinoma (PDAC) mouse models with cachexia. Since muscle is a readily available protein resource during catabolism, we hypothesize there are significant changes in protein sequence and post-translational modifications (PTMs) of muscle proteins during cachexia progression. As these proteins are scavenged, precise analysis of sequence variation can identify the exact mechanism of protein/muscle breakdown and better elucidate the molecular processes of PDAC-induced cachexia. Experimental Design:We performed bioinformatic analysis of two proteomics datasets of cardiac and skeletal muscle samples from PDAC-induced cachexia mouse models. Two proteomics software algorithms, SEQUEST (within Proteome Discoverer (PD)) and PEAKS (a machine-learning algorithm), were used to identify all sample proteins and their PTMs. Because PEAKS can identify more PTMs than PD, we compared the most abundant proteins identified in PD and PEAKS, hypothesizing PEAKS would yield greater protein sequence coverage. Finally, we compiled unpublished PTMs and protein processing events for 25 of the most abundant proteins in both datasets. Results:Notably, PEAKS reported greater sequence coverage for cardiac muscle than PD, while the skeletal muscle sample had similar coverage in both algorithms. This discrepancy may suggest cachectic processes degrade skeletal muscle at a greater rate than cardiac muscle, preventing PEAKS from increasing skeletal muscle sequence coverage relative to PD. In addition, several unpublished modifications, including those of actin and acetyl-CoA acetyltransferase, were recorded. Potential Impact:These newly discovered protein modifications may indicate previously unknown molecular processes in the course of PDAC-induced cachexia. These modifications may serve as cornerstones of future research to identify novel therapeutic targets in cachexia treatment.
背景与假设：恶病质是一种常见于癌症患者的消耗性综合征，不能仅用热量摄入减少来解释。恶病质会导致生活质量下降和死亡率升高，目前尚无有效的治疗方法。为了更好地了解恶病质，我们旨在分析胰腺导管腺癌（PDAC）小鼠恶病质模型中蛋白质的异质性。由于肌肉是分解代谢过程中随时可用的蛋白质资源，我们推测在恶病质进展过程中，肌肉蛋白质的蛋白质序列和翻译后修饰（PTM）会发生显著变化。随着这些蛋白质被清除，对序列变异的精确分析可以确定蛋白质/肌肉分解的确切机制，从而更好地阐明PDAC诱导的恶病质的分子过程。实验设计：我们对PDAC诱导的恶病质小鼠模型的心肌和骨骼肌样本的两个蛋白质组学数据集进行了生物信息学分析。两种蛋白质组学软件算法SEQUEST（蛋白质组发现者（PD））和PEAKS（一种机器学习算法）被用来鉴定所有样本蛋白质及其PTMs。由于 PEAKS 能比 PD 鉴定出更多的 PTM，我们比较了 PD 和 PEAKS 鉴定出的最丰富的蛋白质，假设 PEAKS 会产生更大的蛋白质序列覆盖率。最后，我们汇编了两个数据集中 25 个最丰富蛋白质的未发表 PTM 和蛋白质加工事件。结果：值得注意的是，PEAKS报告的心肌序列覆盖率高于PD，而骨骼肌样本在两种算法中的覆盖率相似。这种差异可能表明，骨骼肌的缓存过程比心肌的降解速度更快，从而阻碍了 PEAKS 提高骨骼肌序列覆盖率。此外，还记录了几种未发表的修饰，包括肌动蛋白和乙酰-CoA乙酰转移酶的修饰。潜在影响：这些新发现的蛋白质修饰可能表明了 PDAC 诱导的恶病质过程中以前未知的分子过程。这些修饰可作为未来研究的基石，以确定治疗恶病质的新靶点。
{"title":"Precision analysis of protein sequence and post-translational modification heterogeneity in pancreatic cancer induced cachexia","authors":"Allyse M. Emmel, Tara S. Umberger, Emma H. Doud, T. Zimmers, Amber L. Mosley","doi":"10.18060/27895","DOIUrl":"https://doi.org/10.18060/27895","url":null,"abstract":"Background and Hypothesis:Cachexia is a wasting syndrome commonly occurring in cancer patients that cannot be explained by decreased calorie intake alone. It results in decreased quality of life and increased mortality, and there are currently no effective treatments. To better understand cachexia, we aimed to profile protein heterogeneity seen in pancreatic ductal adenocarcinoma (PDAC) mouse models with cachexia. Since muscle is a readily available protein resource during catabolism, we hypothesize there are significant changes in protein sequence and post-translational modifications (PTMs) of muscle proteins during cachexia progression. As these proteins are scavenged, precise analysis of sequence variation can identify the exact mechanism of protein/muscle breakdown and better elucidate the molecular processes of PDAC-induced cachexia. \u0000Experimental Design:We performed bioinformatic analysis of two proteomics datasets of cardiac and skeletal muscle samples from PDAC-induced cachexia mouse models. Two proteomics software algorithms, SEQUEST (within Proteome Discoverer (PD)) and PEAKS (a machine-learning algorithm), were used to identify all sample proteins and their PTMs. Because PEAKS can identify more PTMs than PD, we compared the most abundant proteins identified in PD and PEAKS, hypothesizing PEAKS would yield greater protein sequence coverage. Finally, we compiled unpublished PTMs and protein processing events for 25 of the most abundant proteins in both datasets. \u0000Results:Notably, PEAKS reported greater sequence coverage for cardiac muscle than PD, while the skeletal muscle sample had similar coverage in both algorithms. This discrepancy may suggest cachectic processes degrade skeletal muscle at a greater rate than cardiac muscle, preventing PEAKS from increasing skeletal muscle sequence coverage relative to PD. In addition, several unpublished modifications, including those of actin and acetyl-CoA acetyltransferase, were recorded. \u0000Potential Impact:These newly discovered protein modifications may indicate previously unknown molecular processes in the course of PDAC-induced cachexia. These modifications may serve as cornerstones of future research to identify novel therapeutic targets in cachexia treatment.","PeriodicalId":20522,"journal":{"name":"Proceedings of IMPRS","volume":"16 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139534270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Cancer patients frequently develop skeletal muscle wasting and weakness, which are hallmarks of cachexia, a wasting disease which worsens quality of life and is directly responsible for up to 30% of all cancer-related deaths. While advancements in detection and treatment have increased the population of cancer survivors, skeletal muscle dysfunction can persist for years following cancer remission. We previously demonstrated that late-stage cachexia is associated with impaired skeletal muscle innervation, linking loss of motor unit (MU) connectivity to cancer-induced wasting and weakness. In the present study, we investigated the onset of neuromuscular dysfunction in a preclinical model of cancer cachexia. Methods: CD2F1 male mice (8-week-old) were subcutaneously injected with C26 colorectal cancer cells (1.0x106) or saline and randomized into one the following timepoint groups: day 6, day 8, or day 10 (n=8-10). Animals were assessed for indices of MU connectivity and muscle function at each timepoint. Following functional assessment, skeletal muscles were harvested, weighed, and processed for molecular analyses. Results: 6 days post tumor injection, C26 hosts displayed reductions in neuromuscular junction (NMJ) transmission and motor unit connectivity, while muscle torque and mass were preserved. Specific torque was reduced in C26 hosts at day 8, while reductions in muscle mass or cross-sectional area did not occur until day 10. Molecular analysis revealed alterations of NMJ components as early as day 6 in C26 hosts, further suggesting that neuromuscular dysfunction precedes muscle atrophy. Conclusions: Altogether our data demonstrate that cancer-induced neuromuscular dysfunction precedes cancer-induced muscle atrophy, identifying impaired innervation as an early prognosticator of cachexia progression. Our work supports strategies to counteract impaired neuromuscular function in the treatment of cancer cachexia, in hopes of sustaining quality of life in cancer patients and the growing population of cancer survivors.
{"title":"Neuromuscular dysfunction precedes muscle atrophy in C26 tumor-bearing mice","authors":"Davis Giffin, Morgan Clouse, J. Huot","doi":"10.18060/27854","DOIUrl":"https://doi.org/10.18060/27854","url":null,"abstract":"Background: Cancer patients frequently develop skeletal muscle wasting and weakness, which are hallmarks of cachexia, a wasting disease which worsens quality of life and is directly responsible for up to 30% of all cancer-related deaths. While advancements in detection and treatment have increased the population of cancer survivors, skeletal muscle dysfunction can persist for years following cancer remission. We previously demonstrated that late-stage cachexia is associated with impaired skeletal muscle innervation, linking loss of motor unit (MU) connectivity to cancer-induced wasting and weakness. In the present study, we investigated the onset of neuromuscular dysfunction in a preclinical model of cancer cachexia. \u0000Methods: CD2F1 male mice (8-week-old) were subcutaneously injected with C26 colorectal cancer cells (1.0x106) or saline and randomized into one the following timepoint groups: day 6, day 8, or day 10 (n=8-10). Animals were assessed for indices of MU connectivity and muscle function at each timepoint. Following functional assessment, skeletal muscles were harvested, weighed, and processed for molecular analyses. \u0000Results: 6 days post tumor injection, C26 hosts displayed reductions in neuromuscular junction (NMJ) transmission and motor unit connectivity, while muscle torque and mass were preserved. Specific torque was reduced in C26 hosts at day 8, while reductions in muscle mass or cross-sectional area did not occur until day 10. Molecular analysis revealed alterations of NMJ components as early as day 6 in C26 hosts, further suggesting that neuromuscular dysfunction precedes muscle atrophy. \u0000Conclusions: Altogether our data demonstrate that cancer-induced neuromuscular dysfunction precedes cancer-induced muscle atrophy, identifying impaired innervation as an early prognosticator of cachexia progression. Our work supports strategies to counteract impaired neuromuscular function in the treatment of cancer cachexia, in hopes of sustaining quality of life in cancer patients and the growing population of cancer survivors.","PeriodicalId":20522,"journal":{"name":"Proceedings of IMPRS","volume":"33 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139534337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background/Objective:Sciatica affects nearly half of all Americans and can often become debilitating, leading to severe pain that can limit performing activities of daily living. Brace application has not been tried for alleviation of pain. In this study, we seek to find if a novel brace can decrease pain and decrease bothersome level of symptoms for those suffering from sciatica. In addition, this study utilizes a cadaveric dissection to understand how the sciatic nerve stretches and tensions upon lower limb manipulation. Methods:Fourteen patients self-reported pain, functionality, and bothersome levels pre- and post-bracing. Excel’s data analysis tool was utilized to run statistical tests. One cadaver (2 lower limbs) was dissected, revealing the sciatic nerve at the hip and knee, while tibial nerve at the ankle. Excursion was measured utilizing a fixed pin and an initial distance, the leg manipulated, and final distance from pin measured. Ultimately, excursion was deemed final distance minus initial distance from the pin. Results:The brace decreases Visual Analogue Scale (VAS) scores, increases Patient Reported Outcomes, and decreases Sciatica Bothersome Indexes. There was a significant difference in VAS pre- versus post-brace values at initial and 7-day post-visit but not at 21- or 42-day postvisit. Sciatic nerve excursion was greatest at the ankle. Conclusion and Potential Impact:Brace use decreases pain levels, increases functionality, and decreases bothersome level of symptoms. The distal nerve moves more upon manipulation and therefore is more prone to tensioning than the proximal nerve. Dissection data illustrates how the brace positions the limb in a way that promotes “detensioning” of the nerve, alleviating sciatica. More cadaver data is needed.
{"title":"Efficacy of Novel Bracing for Treating Sciatica and Cadaveric Dissection to Examine Excursion of the Sciatic Nerve","authors":"Kyle Callahan, Dale Dellacqua","doi":"10.18060/27891","DOIUrl":"https://doi.org/10.18060/27891","url":null,"abstract":"Background/Objective:Sciatica affects nearly half of all Americans and can often become debilitating, leading to severe pain that can limit performing activities of daily living. Brace application has not been tried for alleviation of pain. In this study, we seek to find if a novel brace can decrease pain and decrease bothersome level of symptoms for those suffering from sciatica. In addition, this study utilizes a cadaveric dissection to understand how the sciatic nerve stretches and tensions upon lower limb manipulation. \u0000Methods:Fourteen patients self-reported pain, functionality, and bothersome levels pre- and post-bracing. Excel’s data analysis tool was utilized to run statistical tests. One cadaver (2 lower limbs) was dissected, revealing the sciatic nerve at the hip and knee, while tibial nerve at the ankle. Excursion was measured utilizing a fixed pin and an initial distance, the leg manipulated, and final distance from pin measured. Ultimately, excursion was deemed final distance minus initial distance from the pin. \u0000Results:The brace decreases Visual Analogue Scale (VAS) scores, increases Patient Reported Outcomes, and decreases Sciatica Bothersome Indexes. There was a significant difference in VAS pre- versus post-brace values at initial and 7-day post-visit but not at 21- or 42-day postvisit. Sciatic nerve excursion was greatest at the ankle. \u0000Conclusion and Potential Impact:Brace use decreases pain levels, increases functionality, and decreases bothersome level of symptoms. The distal nerve moves more upon manipulation and therefore is more prone to tensioning than the proximal nerve. Dissection data illustrates how the brace positions the limb in a way that promotes “detensioning” of the nerve, alleviating sciatica. More cadaver data is needed.","PeriodicalId":20522,"journal":{"name":"Proceedings of IMPRS","volume":"27 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139534358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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