The latest medical research on Neurosurgery

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about neurosurgery gathered by our medical AI research bot.

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Assessment of Use of Arteriovenous Graft vs Arteriovenous Fistula for First-time Permanent Hemodialysis Access.

JAMA Surgery

Initial hemodialysis access with arteriovenous fistula (AVF) is associated with superior clinical outcomes compared with arteriovenous graft (AVG) and should be the procedure of choice whenever possible. To address the national underuse of AVF in the United States, the Centers for Medicare & Medicaid has established an AVF goal of 66% or greater in 2009.

To explore contemporary practice patterns and physician characteristics associated with high AVG use compared with AVF use.

This review of 100% Medicare Carrier claims between January 1, 2016, and December 31, 2017, includes both inpatient and outpatient Medicare claims data. All patients undergoing initial permanent hemodialysis access placement with an AVF or AVG were included. All surgeons performing more than 10 hemodialysis access procedures during the study period were analyzed.

Placement of an AVF or AVG for initial permanent hemodialysis access.

A surgeon-level AVG (vs AVF) use rate was calculated for all included surgeons. Hierarchical logistic regression modeling was used to identify patient-level and surgeon-level factors associated with AVG use.

A total of 85 320 patients (median age, 70 [range, 18-103] years; 47 370 men [55.5%]) underwent first-time hemodialysis access placement, of whom 66 489 (77.9%) had an AVF and 18 831 (22.1%) had an AVG. Among the 2397 surgeons who performed more than 10 procedures per year, the median surgeon level AVG use rate was 18.2% (range, 0.0%-96.4%). However, 498 surgeons (20.8%) had an AVG use rate greater than 34%. After accounting for patient characteristics, surgeon factors that were independently associated with AVG use included more than 30 years of clinical practice (vs 21-30 years; odds ratio, 0.85 [95% CI, 0.75-0.96]), metropolitan setting (odds ratio, 1.25 [95% CI, 1.02-1.54]), and vascular surgery specialty (vs general surgery; odds ratio, 0.77 [95% CI, 0.69-0.86]). Surgeons in the Northeast region had the lowest rate of AVG use (vs the South; odds ratio, 0.83 [95% CI, 0.73-0.96]). First-time hemodialysis access benchmarking reports for individual surgeons were created for potential distribution.

In this study, one-fifth of surgeons had an AVG use rate above the recommended best practices guideline of 34%. Although some of these differences may be explained by patient referral practices, sharing benchmarked performance data with surgeons could be an actionable step in achieving more high-value care in hemodialysis access surgery.

Comparison of Targeted vs Systematic Prostate Biopsy in Men Who Are Biopsy Naive: The Prospective Assessment of Image Registration in the Diagnosis of Prostate Cancer (PAIREDCAP) Study.

JAMA Surgery

Magnetic resonance imaging (MRI) guidance improves the accuracy of prostate biopsy for the detection of clinically significant prostate cancer, but the optimal use of such guidance is not yet clear.

To determine the cancer detection rate (CDR) of targeting MRI-visible lesions vs systematic prostate sampling in the diagnosis of clinically significant prostate cancer in men who were biopsy naive.

This paired cohort trial, known as the Prospective Assessment of Image Registration in the Diagnosis of Prostate Cancer (PAIREDCAP) study, was conducted in an academic medical center from January 2015 to April 2018. Men undergoing first-time prostate biopsy were enrolled. Paired-cohort participants were a consecutive series of men with MRI-visible lesions (defined by a Prostate Imaging Reporting & Data System version 2 score  ≥ 3), who each underwent 3 biopsy methods at the same sitting: first, a systematic biopsy; second, an MRI-lesion biopsy targeted by cognitive fusion; and third, an MRI-lesion targeted by software fusion. Another consecutive series of men without MRI-visible lesions underwent systematic biopsies to help determine the false-negative rate of MRI during the trial period.

The primary end point was the detection rate of clinically significant prostate cancer (Gleason grade group ≥2) overall and by each biopsy method separately. The secondary end points were the effects of the Prostate Imaging Reporting & Data System version 2 grade, prostate-specific antigen density, and prostate volume on the primary end point. Tertiary end points were the false-negative rate of MRI and concordance of biopsy-method results by location of detected cancers within the prostate.

A total of 300 men participated; 248 had MRI-visible lesions (mean [SD] age, 65.5 [7.7] years; 197 were white [79.4%]), and 52 were control participants (mean [SD] age, 63.6 [5.9] years; 39 were white [75%]). The overall CDR was 70% in the paired cohort group, achieved by combining systematic and targeted biopsy results. The CDR by systematic sampling was 15% in the group without MRI-visible lesions. In the paired-cohort group, CDRs varied from 47% (116 of 248 men) when using cognitive fusion biopsy alone, to approximately 60% when using systematic biopsy (149 of 248 men) or either fusion method alone (154 of 248 men), to 70% (174 of 248 men) when combining systematic and targeted biopsy. Discordance of tumor locations suggests that the different biopsy methods detect different tumors. Thus, combining targeting and systematic sampling provide greatest sensitivity for detection of clinically significant prostate cancer. For all biopsy methods, the Prostate Imaging Reporting & Data System version 2 grade and prostate-specific antigen density were directly associated with CDRs, and prostate volume was inversely associated.

An MRI-visible lesion in men undergoing first-time prostate biopsy identifies those with a heightened risk of clinically significant prostate cancer. Combining targeted and systematic biopsy offers the best chances of detecting the cancer.

Role of Hepatic Artery Infusion Chemotherapy in Treatment of Initially Unresectable Colorectal Liver Metastases: A Review.

JAMA Surgery

Although liver metastasis develops in more than half of patients with colorectal cancer, only 15% to 20% of these patients have resectable liver metastasis at presentation. Moreover, patients with initially unresectable colorectal liver metastasis (IU-CRLM) who progress on first-line systemic chemotherapy have limited treatment options. Hepatic arterial infusion chemotherapy (HAIC), in combination with systemic chemotherapy, leverages a multimodality approach to achieving control of hepatic disease and/or expanding resectability in patients with liver-only disease or liver-dominant disease.

Intra-arterial delivery of agents with high first-pass hepatic extraction (eg, floxuridine) limits systemic toxic effects and allows for administration of systemic chemotherapy at near-full doses. Hepatic arterial infusion chemotherapy in conjunction with systemic chemotherapy augments response rates up to 92% in patients who are chemotherapy naive, and up to 85% in pretreated patients with IU-CRLM. In turn, these responses translate into encouraging rates of conversion to resectability (CTR). Prospective trials have reported CTR rates as high as 52% in heavily pretreated patients with IU-CRLM who have an extensive hepatic disease burden. As such, CTR remains a compelling indication for liver-directed chemotherapy in this subset of patients. This review discusses the biological rationale for HAIC, evolution of rational combinations with systemic chemotherapy, contemporary evidence for CTR using HAIC and systemic chemotherapy, juxtaposition with rates of CTR using systemic chemotherapy alone, and morbidity and toxic effect profiles of HAIC.

The argument is made for consideration of earlier initiation of HAIC in patients with IU-CRLM who are chemotherapy naive and for adoption of HAIC strategies to augment rates of resectability in patients who have failed first-line systemic chemotherapy before proceeding to second-line or third-line regimens.

Comparison of Costs of Radical Cystectomy vs Trimodal Therapy for Patients With Localized Muscle-Invasive Bladder Cancer.

JAMA Surgery

Earlier studies on the cost of muscle-invasive bladder cancer treatments lack granularity and are limited to 180 days.

To compare the 1-year costs associated with trimodal therapy vs radical cystectomy, accounting for survival and intensity effects on total costs.

This population-based cohort study used the US Surveillance, Epidemiology, and End Results-Medicare database and included 2963 patients aged 66 to 85 years who had received a diagnosis of clinical stage T2 to T4a muscle-invasive bladder cancer from January 1, 2002, through December 31, 2011. The data analysis was performed from March 5, 2018, through December 4, 2018.

Total Medicare costs within 1 year of diagnosis following radical cystectomy vs trimodal therapy were compared using inverse probability of treatment-weighted propensity score models that included a 2-part estimator to account for intrinsic selection bias.

Of 2963 participants, 1030 (34.8%) were women, 2591 (87.4%) were white, 129 (4.4%) were African American, and 98 (3.3%) were Hispanic. Median costs were significantly higher for trimodal therapy than radical cystectomy in 90 days ($83 754 vs $68 692; median difference, $11 805; 95% CI, $7745-$15 864), 180 days ($187 162 vs $109 078; median difference, $62 370; 95% CI, $55 581-$69 160), and 365 days ($289 142 vs $148 757; median difference, $109 027; 95% CI, $98 692-$119 363), respectively. Outpatient care, radiology, medication expenses, and pathology/laboratory costs contributed largely to the higher costs associated with trimodal therapy. On inverse probability of treatment-weighted adjusted analyses, patients undergoing trimodal therapy had $136 935 (95% CI, $122 131-$152 115) higher mean costs compared with radical cystectomy 1 year after diagnosis.

Compared with radical cystectomy, trimodal therapy was associated with higher costs among patients with muscle-invasive bladder cancer. The differences in costs were largely attributed to medication and radiology expenses associated with trimodal therapy. Extrapolating cost figures resulted in a nationwide excess spending of $468 million for trimodal therapy compared with radical cystectomy for patients who received a diagnosis of bladder cancer in 2017.

Contributors to Postinjury Mental Health in Urban Black Men With Serious Injuries.

JAMA Surgery

Physical injury is associated with postinjury mental health problems, which typically increase disability, cost, recidivism, and self-medication for symptoms.

To determine risk and protective factors across the life span that contribute to depression and posttraumatic stress symptom severity at 3 months after hospital discharge.

This prospective cohort study used a 3-month postdischarge follow-up of patients who had been treated at an urban, level 1 trauma center in the Northeastern United States. Men with injuries who were hospitalized, self-identified as black, were 18 years or older, and resided in the Philadelphia, Pennsylvania, region were eligible and consecutively enrolled. Those who were experiencing a cognitive dysfunction or psychotic disorder, hospitalized because of attempted suicide, or receiving current treatment for depression or posttraumatic stress disorder (PTSD) were excluded. Data were collected from January 2013 to October 2017. Data analysis took place from January 2018 to August 2018.

A serious injury requiring hospitalization; adverse childhood experiences, childhood neighborhood disadvantage, and preinjury physical and mental health; and emotional resources, injury intent, and acute stress responses.

Depression and PTSD symptom severity were assessed with the Quick Inventory of Depressive Symptoms-Self-report and the PTSD Check List-5. The a priori hypothesis was that risk and protective factors are associated with depression and PTSD symptom severity. The analytic approach was structural equation modeling.

A total of 623 black men were enrolled. Of these, 502 participants (80.6%) were retained at 3-month follow-up. Their mean (SD) age was 35.6 (14.9) years; 346 (55.5%) had experienced intentional injuries, and the median (range) Injury Severity Score was 9 (1-45). Of the 500 participants with complete primary outcome data, 225 (45.0%) met the cut point criteria for mental health diagnoses at 3 months. For both mental health outcomes, the models fit the data well (depression: root mean square error of approximation [RMSEA], 0.044; comparative fit index [CFI], 0.93; PTSD: RMSEA = 0.045; CFI = 0.93), and all hypothesized paths were significant and in the hypothesized direction. Outcomes were associated with poor preinjury health (standardized weights: depression, 0.28; P < .001; PTSD, 0.17; P = .02), acute psychological reactions (depression, 0.34; PTSD, 0.38; both P < .001), and intentional injury (depression, 0.16; PTSD, 0.24; both P < .001). Acute psychological reactions were associated with childhood adversity (depression, 0.33; PTSD, 0.36; both P < .001). A history of prior mental health challenges (depression, 0.70; PTSD, 0.70; both P < .001) and psychological or emotional health resources (depression, -0.22; PTSD, -0.23; both P = .003) affected poor preinjury health, which was in turn associated with acute psychological reaction (depression, 0.44; PTSD, 0.42; both P < .001).

The intersection of prior trauma and adversity, prior exposure to neighborhood disadvantage, and poorer preinjury health and functioning are important, even in the midst of acute medical care for traumatic injury. These results support the importance of trauma-informed health care and focused assessment to identified patients with injuries who are at highest risk for poor postinjury mental health outcomes.

To randomize, or not to randomize, that is the question: using data from prior clinical trials to guide future designs.

Neuro-Oncology

Understanding the value of randomization is critical in designing clinical trials. Here, we introduce a simple and interpretable quantitative method to compare randomized designs versus single arm designs using indication-specific parameters derived from the literature. We demonstrate the approach through application to phase II trials in newly diagnosed glioblastoma (ndGBM).

We abstracted data from prior ndGBM trials and derived relevant parameters to compare phase II RCT and single arm designs within a quantitative framework. Parameters included in our model were (i) the variability of the primary endpoint distributions across studies, (ii) potential for incorrectly specifying the single arm trial's benchmark, and (iii) the hypothesized effect size. Strengths and weaknesses of RCT and single arm designs were quantified by various metrics, including power and false positive errors rates.

We applied our method to show that RCTs should be preferred to single arm trials for evaluating overall survival in ndGBM patients based on parameters estimated from prior trials. More generally, for a given effect size, the utility of randomization compared to single arm designs is highly dependent on (i) inter-study variability of the outcome distributions and (ii) on potential errors in selecting standard of care efficacy estimates for single arm studies.

A quantitative framework using historical data is useful in understanding the utility of randomization in designing prospective trials. For typical phase II ndGBM trials using OS as the primary endpoint, randomization should be preferred over single arm designs.

DNA methylation profiling to predict recurrence risk in meningioma: development and validation of a nomogram to optimize clinical management.

Neuro-Oncology

Variability in standard-of-care classifications precludes accurate predictions of early tumor recurrence for individual patients with meningioma, limiting the appropriate selection of patients who would benefit from adjuvant radiotherapy to delay recurrence. We aimed to develop an individualized prediction model of early recurrence risk combining clinical and molecular factors in meningioma.

DNA methylation profiles of clinically annotated tumor samples across multiple institutions were used to develop a methylome model of 5-year recurrence-free survival (RFS). Subsequently, a 5-year meningioma recurrence score was generated using a nomogram that integrated the methylome model with established prognostic clinical factors. Performance of both models was evaluated and compared with standard-of-care models using multiple independent cohorts.

The methylome-based predictor of 5-year RFS performed favorably compared with a grade-based predictor when tested using the 3 validation cohorts (ΔAUC = 0.10, 95% CI: 0.03-0.018) and was independently associated with RFS after adjusting for histopathologic grade, extent of resection, and burden of copy number alterations (hazard ratio 3.6, 95% CI: 1.8-7.2, P < 0.001). A nomogram combining the methylome predictor with clinical factors demonstrated greater discrimination than a nomogram using clinical factors alone in 2 independent validation cohorts (ΔAUC = 0.25, 95% CI: 0.22-0.27) and resulted in 2 groups with distinct recurrence patterns (hazard ratio 7.7, 95% CI: 5.3-11.1, P < 0.001) with clinical implications.

The models developed and validated in this study provide important prognostic information not captured by previously established clinical and molecular factors which could be used to individualize decisions regarding postoperative therapeutic interventions, in particular whether to treat patients with adjuvant radiotherapy versus observation alone.

Targeting the PI3K/Akt/mTOR-pathway with the pan-Akt inhibitor GDC-0068 in PIK3CA-mutant breast cancer brain metastases.

Neuro-Oncology

Activating mutations in the PI3K/AKT/mTOR-pathway occur in 43-70% of breast cancer brain metastasis patients. To date, the treatment of these patients presents an ongoing challenge, mainly because of the lack of targeted agents that are able to sufficiently penetrate the blood-brain barrier. GDC-0068 is a pan-Akt-inhibitor that has shown to be effective in various preclinical tumor models as well as in clinical trials. The purpose of this study was to analyze the efficacy of GDC-0068 in a breast cancer brain metastases model.

In in vitro studies, antitumor activity of GDC-0068 was assessed in PIK3CA-mutant and PIK3CA-wildtype breast cancer cell lines using cell viability and apoptosis assays, cell cycle analysis and Western blots. In vivo, the efficacy of GDC-0068 was analyzed in a PIK3CA-mutant breast cancer brain metastasis orthotopic xenograft mouse model and evaluated by repeated bioluminescent imaging and immunohistochemistry.

GDC-0068 decreased cell viability, induced apoptosis and inhibited phosphorylation of PRAS40 and p70 S6 kinase in a dose-dependent manner in PIK3CA-mutant breast cancer brain metastatic cell lines compared to PIK3CA-wildtype cell lines. In vivo, treatment with GDC-0068 notably inhibited the growth of PIK3CA-mutant tumors and resulted in a significant survival benefit compared to sham whereas no effect was detected in a PIK3CA-wildtype model.

This study suggests that the Akt-inhibitor GDC-0068 may be an encouraging targeted treatment strategy for breast cancer brain metastasis patients with activating mutations in the PI3K pathway. These data provide a rationale to further evaluate the efficacy of GDC-0068 in patients with brain metastases.

Barriers to Accrual and Enrollment in Brain Tumor Trials.

Neuro-Oncology

Many factors contribute to the poor survival of malignant brain tumor patients, some of which are not easily remedied. However, one contributor to ...

Transition Planning for the Senior Surgeon: Guidance and Recommendations From the Society of Surgical Chairs.

JAMA Surgery

Aging is well documented to be associated with declines in cognitive function and psychomotor performance, but only limited guidance is currently available from medical professional societies or regulatory agencies on how to translate these observations into the appropriate monitoring of physician performance.

The Society of Surgical Chairs conducted a panel discussion at its 2017 annual meeting and a subsequent survey of its membership in 2018 to develop recommendations for the transitioning of the senior surgeon.

Recommendations include mandatory cognitive and psychomotor testing of surgeons by at least age 65 years, potentially as a component of ongoing professional practice evaluation; career transition discussions with surgeons beginning early in their careers; respectful consideration of the potential financial needs, long-standing work commitments, and work-life concerns of retiring surgeons; and creation of teaching, mentoring or coaching, and/or administrative opportunities for senior surgeons in modified clinical or nonclinical roles. Ideally, these initiatives will catalyze a thoughtful and comprehensive new vista in supporting an aging workforce while ensuring the safety of patients, the efficient management of health care organizations, and the avoidance of unnecessary depletions to a sufficiently sized cadre of physicians with case-specific competencies.

Fracture Risk After Roux-en-Y Gastric Bypass vs Adjustable Gastric Banding Among Medicare Beneficiaries.

JAMA Surgery

Roux-en-Y gastric bypass (RYGB) is associated with significant bone loss and may increase fracture risk, whereas substantial bone loss and increased fracture risk have not been reported after adjustable gastric banding (AGB). Previous studies have had little representation of patients aged 65 years or older, and it is currently unknown how age modifies fracture risk.

To compare fracture risk after RYGB and AGB procedures in a large, nationally representative cohort enriched for older adults.

This population-based retrospective cohort analysis used Medicare claims data from January 1, 2006, to December 31, 2014, from 42 345 severely obese adults, of whom 29 624 received RYGB and 12 721 received AGB. Data analysis was performed from April 2017 to November 2018.

The primary outcome was incident nonvertebral (ie, wrist, humerus, pelvis, and hip) fractures after RYGB and AGB surgery defined using a combination of International Classification of Diseases, Ninth Edition and Current Procedural Terminology 4 codes.

Of 42 345 participants, 33 254 (78.5%) were women. With a mean (SD) age of 51 (12) years, recipients of RYGB were younger than AGB recipients (55 [12] years). Both groups had similar comorbidities, medication use, and health care utilization in the 365 days before surgery. Over a mean (SD) follow-up of 3.5 (2.1) years, 658 nonvertebral fractures were documented. The fracture incidence rate was 6.6 (95% CI, 6.0-7.2) after RYGB and 4.6 (95% CI, 3.9-5.3) after AGB, which translated to a hazard ratio (HR) of 1.73 (95% CI, 1.45-2.08) after multivariable adjustment. Site-specific analyses demonstrated an increased fracture risk at the hip (HR, 2.81; 95% CI, 1.82-4.49), wrist (HR, 1.70; 95% CI, 1.33-2.14), and pelvis (HR, 1.48; 95% CI, 1.08-2.07) among RYGB recipients. No significant interactions of fracture risk with age, sex, diabetes status, or race were found. In particular, adults 65 years and older showed similar patterns of fracture risk to younger adults. Sensitivity analyses using propensity score matching showed similar results (nonvertebral fracture: HR 1.75; 95% CI, 1.22-2.52).

This study of a large, US population-based cohort including a substantial population of older adults found a 73% increased risk of nonvertebral fracture after RYGB compared with AGB, including increased risk of hip, wrist, and pelvis fractures. Fracture risk was consistently increased among RYGB patients vs AGB across different subgroups, and to a similar degree among older and younger adults. Increased fracture risk appears to be an important unintended consequence of RYGB.

A systematic review of cross-sectional differences and longitudinal changes to the morphometry of the brain following paediatric traumatic brain injury.

NeuroImage

Paediatric traumatic brain injury (pTBI) is a leading cause of disability for children and young adults. Children are a uniquely vulnerable group w...