159 research outputs found
Methodology used to develop the AANS/CNS management of brain metastases evidence-based clinical practice parameter guidelines
Congress of neurological surgeons systematic review and evidence-based guidelines update on the role of chemotherapeutic management and antiangiogenic treatment of newly diagnosed glioblastoma in adults
QUESTION: What is the role of temozolomide in the management of adult patients (aged 65 and under) with newly diagnosed glioblastoma?
TARGET POPULATION: These recommendations apply to adult patients diagnosed with newly diagnosed glioblastoma.
RECOMMENDATION: Level I: Concurrent and post-irradiation Temozolomide (TMZ) in combination with radiotherapy and post-radiotherapy as described by Stupp et al. is recommended to improve both PFS and OS in adult patients with newly diagnosed GBM. There is no evidence that alterations in the dosing regimen have additional beneficial effect.
QUESTION: Is there benefit to adjuvant temozolomide treatment in elderly patients (\u3e 65 years old?).
TARGET POPULATION: These recommendations apply to adult patients diagnosed with newly diagnosed glioblastoma.
RECOMMENDATION: Level III: Adjuvant TMZ treatment is suggested as a treatment option to improve PFS and OS in adult patients (over 70 years of age) with newly diagnosed GBM.
QUESTION: What is the role of local regional chemotherapy with BCNU biodegradable polymeric wafers in adult patients with newly diagnosed glioblastoma?
TARGET POPULATION: These recommendations apply to adult patients diagnosed with newly diagnosed glioblastoma.
RECOMMENDATION: Level III: There is insufficient evidence for the use of BCNU wafers following resection in patients with newly diagnosed glioblastoma who undergo the Stupp protocol after surgery. Further studies of higher quality are suggested to understand the role of BCNU wafer and other locoregional therapy in the setting of Stupp Protocol.
QUESTION: What is the role of bevacizumab in the adult patient with newly diagnosed glioblastoma?
TARGET POPULATION: These recommendations apply to adult patients diagnosed with newly diagnosed glioblastoma.
RECOMMENDATION: Level I: Bevacizumab in general is not recommended in the initial treatment of adult patients with newly diagnosed GBM. It continues to be strongly recommended that patients with newly diagnosed GBM be enrolled in properly designed clinical trials to assess the benefit of novel chemotherapeutic agents compared to standard therapy
Neuron-glia crosstalk mediate the neurotoxic effects of ketamine via extracellular vesicles
Background: General anesthetics (GA) are associated with neurodevelopmental abnormalities including cell death, cognitive and behavioral changes. There is now powerful evidence for non-cell autonomous mechanisms in almost every pathological condition in the brain, especially relevant to glial cells, mainly astrocytes and microglia, that exhibit structural and functional contacts with neurons. These interactions were recently reported to occur via the secretion of extracellular vesicles (EVs). Here, we employed primary human neural cells to analyze ketamine effects focusing on the functions of glial cells and their polarization/differentiation state. We also explored the roles of extracellular vesicles (EVs) and different components of the BDNF pathway.
Methods: Ketamine effects were analyzed on human neuronal and glial cell proliferation and apoptosis and astrocytic (A1/A2 ) and microglial (M1/M2) cell activation were analyzed. The impact of the neuron-glial cell interactions in the neurotoxic effects of ketamine was analyzed using transwell co-cultures. The role of the brainderived neurotrophic factor (BDNF) pathway, was analyzed using RT-PCR, ELISA western blot and gene silencing. EVs secreted by ketamine-treated cells were isolated, characterized and analyzed for their effects in neuron-glia cell interactions. Data were analyzed using analysis of variance or a Student\u27s t test with correction for data sets with unequal variances.
Results: Ketamine induced neuronal and oligodendrocytic cell apoptosis and promoted the expression of proinflammatory astrocytes (A1) and microglia (M1) phenotypes. Astrocytes and microglia enhanced the neurotoxic effects of ketamine on neuronal cells, whereas neurons increased oligodendrocyte cell death. Ketamine modulated different components in the BDNF pathway: decreasing BDNF secretion in neurons and astrocytes while increasing the expression of p75 in neurons and oligodendrocytes. In addition, ketamine treatment increased the lncRNA BDNF-AS levels and the secretion of pro-BDNF secretion. We found an important role of EVs secreted by ketamine-treated astrocytes in neuronal cell death by delivering BDNF-AS.
Conclusions: Ketamine neurotoxicity involves both autonomous and non-cell autonomous mechanisms andomponents of the BDNF pathway expressed by neurons and glial cells represent major regulators of ketamine effects. We demonstrated for the first time a role of EVs as important mediators of ketamine effects by the delivery of specific non-coding RNAs. These results may contribute to a better understanding of cellular and molecular mechanisms underlying ketamine neurotoxic effects in humans and to the development of potential approaches to decrease its neurodevelopmental impact
Methodology used to develop the AANS/CNS management of brain metastases evidence-based clinical practice parameter guidelines
Onward and Upward: The Legacy of Black Urologists in America
In partnership with the American Urological Association\u27s William P. Didusch Center for Urologic History, Henry Ford Health hosted a Grand Rounds event from 7 – 9 a.m. Wednesday, June 14, in the Buerki Auditorium at Henry Ford Hospital.
The event highlights the contributions of Black urologists to the history of medicine despite systemic racism in the medical field and across the country. Covering the impact of exclusion and segregation in the past, as well as present day issues such as microaggressions and cultural insensitivity, the lecture and discussion calls for a future of successfully integrating medicine to achieve better outcomes for physicians and their patients.
The schedule of the event is as follows:
7 a.m.: Welcome by Craig Rogers, M.D., Chair, Department of Urology, Vattikuti Urology Institute. Introductory remarks by Adnan Munkarah, M.D., President, Care Delivery System and Chief Clinical Officer and Steven Kalkanis, M.D., CEO of Henry Ford Medical Group and CEO of Henry Ford Hospital.
7:10 a.m.: Keynote speaker Arthur L. Burnett II, M.D., MBA., FACS., professor of urology, Johns Hopkins University School of Medicine will present “Onward and Upward: The Legacy of Black Urologists in America.
7:30 a.m.: Panel discussion moderated by Linda McIntire, M.D., President, R. Frank Jones Urological Society, and graduate of Henry Ford urology program, featuring the panelists listed below. Melvin Hollowell, M.D., FACS Dr. Hollowell earned his medical degree in 1959 and has practiced in Detroit for 64 years. At 93 years young, he is still practicing today. Isaac Powell, M.D. Dr. Powell graduated with his medical degree in 1969 and became the first African American graduate from the Henry Ford Hospital urology program in 1974. Conrad Maitland, M.D. Dr. Maitland has been practicing for 40 years and is himself a survivor of prostate cancer - a disease that disproportionately affects Black men. Ray Littleton, M.D. Dr. Littleton joined the senior staff at Henry Ford Hospital in 1980 and helped pioneer minimally invasive surgery by performing the first percutaneous kidney stone removal in Michigan in 1983
Reducing Superfluous Opioid Prescribing Practices After Brain Surgery: It Is Time to Talk About Drugs
BACKGROUND: Opioids are prescribed routinely after cranial surgery despite a paucity of evidence regarding the optimal quantity needed. Overprescribing may adversely contribute to opioid abuse, chronic use, and diversion.
OBJECTIVE: To evaluate the effectiveness of a system-wide campaign to reduce opioid prescribing excess while maintaining adequate analgesia.
METHODS: A retrospective cohort study of patients undergoing a craniotomy for tumor resection with home disposition before and after a 2-mo educational intervention was completed. The educational initiative was composed of directed didactic seminars targeting senior staff, residents, and advanced practice providers. Opioid prescribing patterns were then assessed for patients discharged before and after the intervention period.
RESULTS: A total of 203 patients were discharged home following a craniotomy for tumor resection during the study period: 98 who underwent surgery prior to the educational interventions compared to 105 patients treated post-intervention. Following a 2-mo educational period, the quantity of opioids prescribed decreased by 52% (median morphine milligram equivalent per day [interquartile range], 32.1 [16.1, 64.3] vs 15.4 [0, 32.9], P \u3c .001). Refill requests also decreased by 56% (17% vs 8%, P = .027) despite both groups having similar baseline characteristics. There was no increase in pain scores at outpatient follow-up (1.23 vs 0.85, P = .105).
CONCLUSION: A dramatic reduction in opioids prescribed was achieved without affecting refill requests, patient satisfaction, or perceived analgesia. The use of targeted didactic education to safely improve opioid prescribing following intracranial surgery uniquely highlights the ability of simple, evidence-based interventions to impact clinical decision making, lessen potential patient harm, and address national public health concerns
A Distinct DNA Methylation Shift in a Subset of Glioma CpG Island Methylator Phenotypes during Tumor Recurrence
Glioma diagnosis is based on histomorphology and grading; however, such classification does not have predictive clinical outcome after glioblastomas have developed. To date, no bona fide biomarkers that significantly translate into a survival benefit to glioblastoma patients have been identified. We previously reported that the IDH mutant G-CIMP-high subtype would be a predecessor to the G-CIMP-low subtype. Here, we performed a comprehensive DNA methylation longitudinal analysis of diffuse gliomas from 77 patients (200 tumors) to enlighten the epigenome-based malignant transformation of initially lower-grade gliomas. Intra-subtype heterogeneity among G-CIMP-high primary tumors allowed us to identify predictive biomarkers for assessing the risk of malignant recurrence at early stages of disease. G-CIMP-low recurrence appeared in 9.5% of all gliomas, and these resembled IDH-wild-type primary glioblastoma. G-CIMP-low recurrence can be characterized by distinct epigenetic changes at candidate functional tissue enhancers with AP-1/SOX binding elements, mesenchymal stem cell-like epigenomic phenotype, and genomic instability. Molecular abnormalities of longitudinal G-CIMP offer possibilities to defy glioblastoma progression
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