The latest medical research on Neurosurgery
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Perceptions of Surgery Residents About Parental Leave During Training.JAMA Surgery
- design, setting, and participants
- main outcomes and measures
- conclusions and relevance
To our knowledge, there has been little research conducted on the attitudes of residents toward their pregnant peers and parental leave.
To examine the perceptions of current surgery residents regarding parental leave.
A 36-item survey was distributed to current US general surgery residents and residents in surgical subspecialties through the Association of Program Directors in Surgery listserv and social media platforms. Questions were associated with general information/demographics, parental leave, having children, and respondents' knowledge regarding the current parental leave policy as set by the American Board of Surgery. The study was conducted from August to September 2018 and the data were analyzed in October 2018.
Main outcomes included the attitudes of residents toward pregnancy and parental leave, parental leave policy, and the association of parental leave with residency programs.
A total of 2188 completed responses were obtained; of these, 1049 (50.2%) were women, 1572 (75.8%) were white, 164 (7.9%) were Hispanic/Latinx, 75 (3.6%) were African American, 2 (0.1%) were American Indian or Alaskan Native, 263 (12.7%) were Asian, and 5 (0.2%) were Native Hawaiian or Pacific Islander. From the number of residents who had/were expecting children (581 [28.6%]), 474 (81.6%) had or were going to have a child during the clinical years of residency. Many residents (247 [42.5%]) took fewer than 2 weeks of parental leave. Many residents did not feel supported in taking parental leave (177 [30.4%] did not feel supported by other residents and 190 [32.71%] did not feel supported by the faculty). Only 83 respondents (3.8%%) correctly identified the current American Board of Surgery parental leave policy. Residents who took parental leave identified a lack of a universal leave policy, strain on the residency program, a loss of education/training time, a lack of flexibility of programs, and a perceived or actual lack of support from faculty/peers as the top 5 biggest obstacles to taking leave during the clinical years of residency.
Most of the modifiable factors that inhibit residents from having children during residency are associated with policies (eg, a lack of universal leave policy and lack of flexibility) and personnel (eg, a strain on the residency program and lack of support from peers/faculty). These data suggest that policies at the level of the Accreditation Council for Graduate Medical Education or Resident Review Committee (RRC), as well as education and the normalization of pregnancy during training, may be effective interventions.
Association of Residents' Neural Signatures With Stress Resilience During Surgery.JAMA Surgery
- design, setting, and participants
- main outcomes and measures
- conclusions and relevance
Intraoperative stressors may compound cognitive load, prompting performance decline and threatening patient safety. However, not all surgeons cope equally well with stress, and the disparity between performance stability and decline under high cognitive demand may be characterized by differences in activation within brain areas associated with attention and concentration such as the prefrontal cortex (PFC).
To compare PFC activation between surgeons demonstrating stable performance under temporal stress with those exhibiting stress-related performance decline.
Cohort study conducted from July 2015 to September 2016 at the Imperial College Healthcare National Health Service Trust, England. One hundred two surgical residents (postgraduate year 1 and greater) were invited to participate, of which 33 agreed to partake.
Participants performed a laparoscopic suturing task under 2 conditions: self-paced (SP; without time-per-knot restrictions), and time pressure (TP; 2-minute per knot time restriction).
A composite deterioration score was computed based on between-condition differences in task performance metrics (task progression score [arbitrary units], error score [millimeters], leak volume [milliliters], and knot tensile strength [newtons]). Based on the composite score, quartiles were computed reflecting performance stability (quartile 1 [Q1]) and decline (quartile 4 [Q4]). Changes in PFC oxygenated hemoglobin concentration (HbO2) measured at 24 different locations using functional near-infrared spectroscopy were compared between Q1 and Q4. Secondary outcomes included subjective workload (Surgical Task Load Index) and heart rate.
Of the 33 participants, the median age was 33 years, the range was 29 to 56 years, and 27 were men (82%). The Q1 residents demonstrated task-induced increases in HbO2 across the bilateral ventrolateral PFC (VLPFC) and right dorsolateral PFC in the SP condition and in the VLPFC in the TP condition. In contrast, Q4 residents demonstrated decreases in HbO2 in both conditions. The magnitude of PFC activation (change in HbO2) was significantly greater in Q1 than Q4 across the bilateral VLPFC during both SP (mean [SD] left VLPFC: Q1, 0.44 [1.30] μM; Q4, -0.21 [2.05] μM; P < .001; right VLPFC: Q1, 0.46 [1.12] μM; Q4, -0.15 [2.14] μM; P < .001) and TP (mean [SD] left VLPFC: Q1, 0.44 [1.36] μM; Q4, -0.03 [1.83] μM; P = .001; right VLPFC: Q1, 0.49 [1.70] μM; Q4, -0.32 [2.00] μM; P < .001) conditions. There were no significant between-group differences in Surgical Task Load Index or heart rate in either condition.
Performance stability within TP is associated with sustained prefrontal activation indicative of preserved attention and concentration, whereas performance decline is associated with prefrontal deactivation that may represent task disengagement.
Efficacy of EGFR plus TNF inhibition in a preclinical model of temozolomide-resistant glioblastoma.Neuro-Oncology
Glioblastoma (GBM) is the most common primary malignant adult brain tumor. Temozolomide (TMZ) is the standard of care and is most effective in GBMs that lack the DNA repair protein MGMT. Moreover, even initially responsive tumors develop a secondary resistance to TMZ and become untreatable. Since aberrant EGFR signaling is widespread in GBM, EGFR inhibition has been tried in multiple clinical trials without success. We recently reported that inhibiting EGFR leads to increased secretion of TNF and activation of a survival pathway in GBM. Here, we compare the efficacy of TMZ versus EGFR plus TNF inhibition in an orthotopic mouse model of GBM.
We use an orthotopic model to examine the efficacy of TMZ versus EGFR plus TNF inhibition in multiple subsets of GBMs including MGMT methylated and unmethylated primary GBMs, recurrent GBMs and GBMs rendered experimentally resistant to TMZ.
The efficacy of the two treatments was similar in MGMT methylated GBMs. However, in MGMT unmethylated GBMs, a combination of EGFR plus TNF inhibition was more effective. We demonstrate that the two treatment approaches target distinct and non-overlapping pathways. Thus, importantly, EGFR plus TNF inhibition remains effective in TMZ resistant recurrent GBMs and in GBMs rendered experimentally resistant to TMZ.
EGFR inhibition combined with a blunting of the accompanying TNF-driven adaptive response could be a viable therapeutic approach in MGMT unmethylated and recurrent EGFR-expressing GBMs.
Temporal muscle thickness is an independent prognostic marker in patients with progressive glioblastoma: translational imaging analysis of the EORTC 26101 trial.Neuro-Oncology
Temporal muscle thickness (TMT) was described as surrogate marker of skeletal muscle mass. This study aimed to evaluate the prognostic relevance of TMT in patients with progressive glioblastoma.
TMT was analyzed on cranial magnetic resonance images of 596 patients with progression of glioblastoma after radio-chemotherapy enrolled in the EORTC 26101 trial. An optimal TMT cutoff for overall survival (OS) and progression free survival (PFS) was defined in the training cohort (n=260, phase 2). Patients were grouped as "below" or "above" the TMT cutoff and associations with OS and PFS were tested using the Cox model adjusted for important risk factors. Findings were validated in a test cohort (n=308, phase 3).
An optimal baseline TMT cutoff of 7.2 mm was obtained in the training cohort for both OS and PFS (AUC=0.64). Univariate analyses estimated a hazard ratio (HR) of 0.54 (95% CI: 0.42, 0.70, p<0.0001) for OS and a HR of 0.49 (95% CI: 0.38, 0.64, p<0.0001) for PFS for the comparison of training cohort patients above versus below the TMT cutoff. Similar results were obtained in Cox models adjusted for important risk factors with relevance in the trial for OS (HR of 0.54, 95% CI: 0.41, 0.70, p<0.0001) and PFS (HR of 0.47, 95% CI: 0.36, 0.61, p<0.0001). Results were confirmed in the validation cohort.
Reduced TMT is an independent negative prognostic parameter in patients with progressive glioblastoma and may help to facilitate patient management by supporting patient stratification for therapeutic interventions or clinical trials.
Chronic kidney disease in the pathogenesis of acute ischemic stroke.J Cereb Blood
Chronic kidney disease has a graded and independent inverse impact on cerebrovascular health. Both thrombotic and hemorrhagic complications are hig...
Empathy in stroke rats is modulated by social settings.J Cereb Blood
Rodents display "empathy" defined as perceived physical pain or psychological stress by cagemates when co-experiencing socially distinct traumatic ...
Risk Factors For Childhood And Adult Primary Brain Tumors.Neuro-Oncology
Primary brain tumors account for ~1% of new cancer cases and ~2% of cancer deaths in the United States; however, they are the most commonly occurri...
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The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients.Neuro-Oncology
Accurate pathologic diagnoses, and molecularly informed treatment decisions for a wide variety of cancers, depend on robust clinical molecular test...
Establishment of patient-derived orthotopic xenograft model of 1q+ posterior fossa group A ependymoma.Neuro-Oncology
Treatment for pediatric posterior fossa group A (PFA) ependymoma with gain of chromosome 1q (1q+) has not improved over the past decade owed partially to lack of clinically relevant models. We described the first two 1q+ PFA cell lines, which has significantly enhanced our understanding of PFA tumor biology and provided a tool to identify specific 1q+ PFA therapies. However, cell lines do not accurately replicate the tumor microenvironment. Our present goal is to establish patient-derived xenograft (PDX) mouse models.
Disaggregated tumors from two 1q+ PFA patients were injected into the flanks of NSG mice. Flank tumors were then transplanted into the 4th ventricle or lateral ventricle of NSG mice. Characterization of intracranial tumors was performed using imaging, histology, and bioinformatics.
MAF-811_XC and MAF-928_XC established intracranially within the 4th ventricle and retained histological, methylomic, and transcriptomic features of primary patient tumors. We tested the feasibility of treating PDX mice with fractionated radiation or chemotherapy. Mice tolerated radiation despite significant tumor burden, and follow-up imaging confirmed radiation can reduce tumor size. Treatment with Fluorouracil reduced tumor size but did not appear to prolong survival.
MAF-811_XC and MAF-928_XC are novel, authentic, and reliable models for studying 1q+ PFA1 in vivo. Given the successful response to radiation, these models will be advantageous for testing clinically relevant combination therapies to develop future clinical trials for this high-risk subgroup of pediatric ependymoma.
Targeting Hypoxia Downstream Signaling Protein, CAIX, for CAR-T Cell Therapy against Glioblastoma.Neuro-Oncology
Glioblastoma survival remains unchanged despite continuing therapeutic innovation. Herein, we aim to 1) develop CAR-T cells with a specificity to a unique antigen, carbonic anhydrase IX (CAIX), which is expressed in the hypoxic microenvironment characteristic of glioblastoma, and 2) demonstrate its efficacy with limited off-target effects.
First we demonstrated expression of CAIX in patient-derived glioblastoma samples and available databases. CAR-T cells were generated against CAIX and efficacy was assessed in four glioblastoma cell lines and two glioblastoma stem cell lines. Cytotoxicity of anti-CAIX CAR-T cells was assessed via IFN-γ, TNF-α, and IL-2 levels when co-cultured with tumor cells. Finally, we assessed efficacy of direct intra-tumoral injection of the anti-CAIX CAR-T cells on an in vivo xenograft mouse model using the U251 fluorescent cell line. Tumor infiltrating lymphocyte analyses were performed.
We confirm that CAIX is highly expressed in glioblastoma from patients. We demonstrate that CAIX is a suitable target for CAR-T therapy using anti-CAIX CAR-T cells against glioblastoma in vitro and in vivo. In our mouse model, a 20% cure rate was observed without detectable systemic effects.
By establishing the specificity of CAIX under hypoxic conditions in glioblastoma and highlighting its efficacy as a target for CAR-T therapy, our data suggest that anti-CAIX CAR-T may be a promising strategy to treat glioblastoma. Direct intra-tumoral injection increases anti-CAIX CAR-T potency while limiting its off-target effects.
Germline genetic landscape of pediatric central nervous system (CNS) tumors.Neuro-Oncology
Central nervous system (CNS) tumors are the second most common type of cancer among children. Depending on histopathology, anatomic location, and g...