Head-to-head trial of pegunigalsidase alfa versus agalsidase beta in patients with Fabry disease and deteriorating renal function: results from the 2-year randomised phase III BALANCE study.

BACKGROUND: Pegunigalsidase alfa is a PEGylated α-galactosidase A enzyme replacement therapy. BALANCE (NCT02795676) assessed non-inferiority of pegunigalsidase alfa versus agalsidase beta in adults with Fabry disease with an annualised estimated glomerular filtration rate (eGFR) slope more negative than -2 mL/min/1.73 m2/year who had received agalsidase beta for ≥1 year. METHODS: Patients were randomly assigned 2:1 to receive 1 mg/kg pegunigalsidase alfa or agalsidase beta every 2 weeks for 2 years. The primary efficacy analysis assessed non-inferiority based on median annualised eGFR slope differences between treatment arms. RESULTS: Seventy-seven patients received either pegunigalsidase alfa (n=52) or agalsidase beta (n=25). At baseline, mean (range) age was 44 (18-60) years, 47 (61%) patients were male, median eGFR was 74.5 mL/min/1.73 m2 and median (range) eGFR slope was -7.3 (-30.5, 6.3) mL/min/1.73 m2/year. At 2 years, the difference between median eGFR slopes was -0.36 mL/min/1.73 m2/year, meeting the prespecified non-inferiority margin. Minimal changes were observed in lyso-Gb3 concentrations in both treatment arms at 2 years. Proportions of patients experiencing treatment-related adverse events and mild or moderate infusion-related reactions were similar in both groups, yet exposure-adjusted rates were 3.6-fold and 7.8-fold higher, respectively, with agalsidase beta than pegunigalsidase alfa. At the end of the study, neutralising antibodies were detected in 7 out of 47 (15%) pegunigalsidase alfa-treated patients and 6 out of 23 (26%) agalsidase beta-treated patients. There were no deaths. CONCLUSIONS: Based on rate of eGFR decline over 2 years, pegunigalsidase alfa was non-inferior to agalsidase beta. Pegunigalsidase alfa had lower rates of treatment-emergent adverse events and mild or moderate infusion-related reactions. TRIAL REGISTRATION NUMBER: NCT02795676.

Estimated Glomerular Filtration Rate Slope as an Endpoint in Cardiovascular Trials.

PURPOSE OF REVIEW: End stage kidney disease can be a slow process and it may be challenging to achieve required follow-up for sufficient events. Therefore, a surrogate kidney endpoint, such as estimated glomerular filtration rate (eGFR) slope maybe attractive to assess the kidney in cardiovascular trials, especially heart failure (HF). RECENT FINDINGS: eGFR slope can generate informative results in a shorter follow-up period, has decreased risk of type-2 error, and is less sensitive to eGFR shifts compared with other surrogate kidney endpoints (eGFR decline≥40% or doubling creatinine). However, eGFR slope has its limitations with acute effects, heterogeneity in slope calculation/reporting, and deviations from linearity. eGFR slope is a kidney endpoint which may be well-suited for HF trials. Cross-collaborated guideline recommendations are needed to optimize the use of eGFR slope as a kidney endpoint in patients with HF.

Effect of perioperative anticoagulant prophylaxis in patients with traumatic subdural hematoma and a history of anticoagulant use: a propensity-matched National Trauma Data Bank analysis.

OBJECTIVE: The use of anticoagulation to prevent venous thromboembolism (VTE) is controversial in the setting of neurosurgical decompression for traumatic subdural hematoma (SDH). In these patients, there is concern that anticoagulation may cause secondary hemorrhage, increasing the risk of death and other complications. Patients with a history of anticoagulant use are at further risk of VTE, but the effect of VTE prophylaxis (VTEP) following neurosurgery for SDH has not been thoroughly investigated in this population. This study aims to investigate the differences in in-hospital outcomes in patients with SDH and preexisting anticoagulant use who received VTEP following neurosurgical intervention compared with those who did not. METHODS: The National Trauma Data Bank was queried from 2017 to 2019 for all patients with preexisting anticoagulant use presenting with an SDH who subsequently underwent neurosurgical intervention. Patients who received VTEP were propensity score matched with patients who did not based on demographics, insurance type, injury severity, and comorbidities. Paired Student t-tests, Pearson's chi-square tests, and Benjamini-Hochberg multiple comparisons correction were used to compare differences in in-hospital complications, length of stay (LOS), and mortality rate between the two groups. A logistic regression model was developed to identify risk factors for in-hospital mortality. RESULTS: Two thousand seven hundred ninety-four patients matching the inclusion criteria were identified, of whom 950 received VTEP. Following one-to-one matching and multiple comparisons correction, the VTEP group had a lower mortality rate (18.53% vs 34.53%, p < 0.001) but longer LOS (14.09 vs 8.57 days, p < 0.001) and higher rates of pressure ulcers (2.11% vs 0.53%, p = 0.01), unplanned intensive care unit admission (9.05% vs 3.47%, p < 0.001), and unplanned intubation (9.47% vs 6.11%, p = 0.021). The multivariable logistic regression showed that use of unfractionated heparin (UH; OR 0.36, p < 0.001) and low-molecular-weight heparin (LMWH; OR 0.3, p < 0.001) were associated with lower odds of in-hospital mortality. CONCLUSIONS: In patients with traumatic SDH and a history of anticoagulant use, perioperative VTEP was associated with increased LOS but provided a mortality benefit. LMWH and UH use were the strongest predictors of survival.

Racial disparities in incidence, treatment, and survival in adult brain metastases: a 10-year national database analysis.

OBJECTIVE: The aim of this study was to assess demographic and racial disparities in incidence, treatment, and survival of adults with metastatic malignancy to the brain. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) Program database, the authors identified adults with nonprimary brain metastases between 2010 and 2019. Incidence was calculated for all 10 years while data from 2010 to 2014 were used for survival analysis. The primary outcome measure was all-cause mortality within 5 years, assessed by 6-month, 1-year, 2-year, and 5-year survival rates. Chi-square tests of independence and one-way ANOVA were used to compare categorical and continuous measures, respectively, between non-Hispanic White (NHW), Hispanic White (HW), Black, and Asian/Pacific Islander (API) patients. A multivariable Cox proportional hazards model was developed to evaluate the risk of death within 5 years. RESULTS: A total of 64,690 patient records were identified and analyzed following exclusion based on age (patients > 84 years or < 18 years were excluded), missing race data, and missing survival data. Incidences are reported per 100,000 adults. The incidence of brain metastases increased from 2.59 in 2010 to 2.78 in 2019, with an average 10-year incidence of 2.72. API patients had the highest population-adjusted incidence (3.52), followed by NHW (2.99), Black (2.32), and HW (1.59) patients. Black patients were the most likely to have low income and single status, while API patients were the most likely to have high income and married status. Subsequently, Black patients had the shortest survival time (9.05 months vs 9.19 months for NHW vs 12.93 months for HW vs 15.89 months for API patients, p < 0.001). After controlling for the effect of socioeconomic factors on survival, the multivariable analysis showed that Black (HR 0.91, 95% CI 0.88-0.94), HW (HR 0.73, 95% CI 0.69-0.76), and API (HR 0.69, 95% CI 0.66-0.73) patients all had a survival advantage compared with NHW patients. Surgery also conferred a strong survival advantage (HR 0.47, 95% CI 0.44-0.49). CONCLUSIONS: The incidence of brain metastases has increased slightly between 2010 and 2019, with the highest rate in API patients. Black patients had the lowest survival, potentially due to poor socioeconomic status and lower rates of surgery and chemotherapy. Black patients were the most likely to not be recommended surgery, suggesting a discrepancy in services offered to these patients. More research is warranted to understand the underlying causes of these disparities.

Characteristics of work-related spine injury in the USA: a National Trauma Data Bank analysis.

PURPOSE: Workplace injury is a commonplace occurrence in the USA. Spine injuries are especially devastating as they can cause chronic pain and limit mobility which prevents patients from returning to work. Gaining a better understanding of the patients, mechanisms, and treatments associated with these injuries can aid in improving outcomes. The purpose of this study is to characterize the nature of work-related spine injuries. METHODS: The National Trauma Data Bank was queried from 2017 to 2019 for all diagnoses involving the cervical, thoracic, lumbar, and sacral spine. Patient demographics, comorbidities, injury characteristics, spinal diagnoses, and procedures were identified for each occupation. Occupational industries, patient demographics, mechanisms of injury, diagnoses, and spinal procedures were characterized. RESULTS: A total of 100,842 work-related injuries were identified between 2017 and 2019. Of those, 19,002 (19%) were spine injuries, and subsequently, 3963 (21%) required spinal surgery. Eight thousand twenty-nine (42%) cases were seen among construction workers, which had the highest proportion of Hispanic patients (36%). Smoking was prevalent in labor-intensive occupations with high rates of spine injury such as building and grounds maintenance. The most common mechanism of injury was a fall from a roof. The most common injury diagnoses were L1, L2, and L3 fractures, and the most common procedures were T12-L1 fusion, multilevel thoracic fusion, and multilevel lumbar fusion. CONCLUSION: Spine injuries represent a significant portion of work-related injuries in the USA and a considerable portion require neurosurgical intervention. Initial efforts should focus on the prevention and management of lumbar spine injuries in the construction industry.

Outcomes of patients undergoing single-level arthroplasty versus anterior lumbar interbody fusion.

BACKGROUND: Compared to vertebral body fusion, artificial discs are thought to lessen the risks of adjacent segment disease and the need for additional surgery by maintaining spinal mobility as they mimic the intervertebral disc structure. No studies have compared the rates of postoperative complications and the requirement for secondary surgery at adjacent segments among patients who have undergone anterior lumbar interbody fusions (ALIF) versus those undergoing lumbar arthroplasty. METHODS: An all-payer claims database identified 11,367 individuals who underwent single-level ALIF and lumbar arthroplasty for degenerative disc disease (DDD) between January 2010 and October 2020. Rates of complications following surgery, the need for additional lumbar surgeries, length of stay (LOS), and postoperative opioid utilization were assessed in matched cohorts based on logistic regression models. Kaplan-Meyer plots were created to model the probability of additional surgery. RESULTS: Following 1:1 exact matching, 846 records of patients who had undergone ALIF or lumbar arthroplasty were analyzed. All-cause readmission within 30-30 days following surgery was significantly higher in patients undergoing ALIF versus arthroplasty (2.6% vs. 0.71%, p = 0.02). LOS was significantly lower among the patients who had undergone ALIF (1.043 ± 0.21 vs. 2.17 ± 1.7, p < .001). CONCLUSIONS: ALIF and lumbar arthroplasty procedures are equally safe and effective in treating DDD. Our findings do not support that single-level fusions may biomechanically necessitate revisional surgeries.

The role of bone mineral density in adult spinal deformity patients undergoing corrective surgery: a matched analysis.

STUDY DESIGN: Retrospective cohort. BACKGROUND: Over 44 million adults are estimated to have either osteoporosis or osteopenia. Adult spinal deformity (ASD) is estimated to affect between 32 and 68% of the elderly population. OBJECTIVE: Retrospective investigation comparing rates of postoperative complications following thoracolumbar scoliosis surgery in patients with normal bone mineral density (BMD) to those with osteopenia or osteoporosis in addition to analyzing the effects of pretreatment with anti-osteoporotic medications in patients with low BMD. METHODS: Using administrative database of Humana beneficiaries, ICD-9 and ICD-10 diagnosis codes were used to identify ASD patients undergoing multilevel thoracolumbar fusions between 2007 and 2017. RESULTS: The propensity matched population analyzed in this study contained 1044 patients equally represented by those with a history of osteopenia, osteoporosis, or normal BMD. Osteopenia and osteoporosis were associated with increased odds of revision surgery (OR 2.01 95% CI 1.36-2.96 and OR 1.57, 95% CI 1.05-2.35), respectively. Similarly, there was an almost twofold increased odds of proximal and distal junctional kyphosis in patients with osteopenia and osteoporosis (OR 1.95, 95% CI 1.40-2.74 and OR 1.88, 95% CI 1.34-2.64), respectively. A total of 258 (37.1%) patients with osteoporosis were pretreated with anti-osteoporotic medications and there was no statistically significant decrease in odds of proximal or distal junctional kyphosis or revision surgery in these patients. CONCLUSION: Patients with ASD undergoing multilevel thoracolumbar fusion surgery have significantly higher rates of postoperative pseudarthrosis, proximal and distal junctional kyphosis, and revision surgery rates compared to patients with normal BMD.

Comparison of Patiromer to Sodium Polystyrene Sulfonate in Acute Hyperkalemia.

Background: Patiromer and sodium polystyrene sulfonate (SPS) are cation-exchangers approved for the treatment of chronic hyperkalemia. Data regarding their efficacy acutely is lacking. Despite this, both drugs are frequently used in the emergent setting. Objective: The purpose of this study was to compare the potassium reduction of patiromer to SPS within 6 to 24 hours following a single dose. Methods: This retrospective quality improvement project included hyperkalemic patients receiving 1 dose of patiromer or SPS and had a second potassium level drawn in 6 to 24 hours. Doses of 8.4 g of patiromer and 15 g of SPS were considered "low dose" while 16.8 g of patiromer and 30 g of SPS were considered "high dose." The presence of a dose-response relationship was assessed through a linear regression analysis. Results: Mean (SD) potassium reduction was higher in SPS than patiromer [0.76 (0.63) mEq/L vs 0.32 (0.65) mEq/L, (P = .001)]. A dose response relationship was not demonstrated in low versus high dose groups [-0.21 (0.14), P = .13] and CKD, ESRD, and renal transplant patients when compared to patients with normal renal function [0.11 (0.17), P = .51, -0.07 (0.19), P = -0.07 (0.19), P = .73, and -0.10 (0.22), P = .65]. Conclusions: This study suggests a clinically significant reduction in potassium with SPS compared to patiromer. Although SPS was successful in demonstrating this outcome, due to well-documented adverse reactions in the literature and a time to onset of 6 hours, it cannot be recommended for use in acute hyperkalemia either.

Pediatric primary high-grade spinal glioma: a National Cancer Database analysis of current patterns in treatment and outcomes.

PURPOSE: Pediatric primary high-grade spinal glioma (p-HGSG) is an extremely rare disease process, with little data within the current literature. Akin to primary high-grade gliomas, this cancer has been exemplified by dismal prognosis and poor response to modern treatment paradigms. This study seeks to investigate the current trends affecting overall survival using the National Cancer Database (NCDB). METHODS: The NCDB was queried for p-HGSG between 2004 and 2016, by utilizing the designated diagnosis codes. Kaplan-Meier curves were generated, and log-rank testing was performed to analyze factors affecting overall survival. In addition, a Cox proportional-hazards model was used to perform multivariate regression analysis of survival outcomes. RESULTS: A cohort of 97 patients was identified with a histologically confirmed p-HGSG. The overall incidence of p-HGSG in all pediatric spinal cord tumors is 7.5%, with a mean survival time of 25.3 months (SD, 21.0) and 5-year overall survival of 17.0%. The majority of patients underwent surgery (n = 87, 89.7%), radiotherapy (n = 73, 75.3%), and chemotherapy (n = 60, 61.9%). Univariate, multivariate, and Kaplan-Meier log-rank testing failed to demonstrate an association between performing surgery, extent of resection, radiotherapy, or chemotherapy with improved survival outcomes. CONCLUSIONS: The current study constitutes the largest retrospective analysis of p-HGSGs to date, finding that current treatment options of surgery, radiotherapy, and chemotherapy have unclear benefit. This disease process has a poor prognosis without a current modality of treatment that conclusively alters survival. The risks and side effects of these treatment modalities must be carefully considered in such a highly aggressive disease process, especially given potentially limited survival benefits.

Adult primary high-grade spinal glioma: a nationwide analysis of current trends in treatment and outcomes.

PURPOSE: High-grade spinal glioma (HGSG) is an extremely rare, malignant neoplasm insufficiently described in the literature. We sought to investigate the effect of epidemiological risk factors and treatment strategies on the prognosis of HGSGs using the National Cancer Database (NCDB). METHODS: Patients with diagnosis codes specific for HGSG were queried from the NCDB during the years 2004-2016. Kaplan-Meier curves were generated with log-rank testing performed to assess factors affecting survival. Univariate and multivariate Cox regression analysis was also performed to investigate overall survival. RESULTS: 396 patients were identified with a histologically-confirmed diagnosis of HGSG between 2004-2016. The mean survival time for all patients was 24.5 months (SD: 20.3). Multivariate Cox proportional-hazards regression analysis revealed that tumor size of 26-50 mm (HR 4.96, 95% CI 1.76-13.98, p < 0.01) and greater than 50 mm (HR 4.67, 95% CI 1.43-15.23, p = 0.01) were associated with worsened overall survival in comparison to lesions less than 26 mm. While quality of life was not investigated, both Kaplan-Meier log-rank testing and regression analysis failed to demonstrate an association of survival outcomes with extent of resection, radiotherapy, or chemotherapy. CONCLUSION: The current study represents the largest retrospective analysis of adult primary high-grade spinal glioma to date. Our analysis found no relationship between the extent of surgical resection and survival outcomes. In addition, we failed to show any statistically significant survival benefit with radiotherapy or chemotherapy. This disease process has a poor prognosis without a current modality of treatment that improves survival.

Unravelling stacking order in epitaxial bilayer MX2 using 4D-STEM with unsupervised learning.

Following an extensive investigation of various monolayer transition metal dichalcogenides (MX2), research interest has expanded to include multilayer systems. In bilayer MX2, the stacking order strongly impacts the local band structure as it dictates the local confinement and symmetry. Determination of stacking order in multilayer MX2 domains usually relies on prior knowledge of in-plane orientations of constituent layers. This is only feasible in case of growth resulting in well-defined triangular domains and not useful in-case of closed layers with hexagonal or irregularly shaped islands. Stacking order can be discerned in the reciprocal space by measuring changes in diffraction peak intensities. Advances in detector technology allow fast acquisition of high-quality four-dimensional datasets which can later be processed to extract useful information such as thickness, orientation, twist and strain. Here, we use 4D scanning transmission electron microscopy combined with multislice diffraction simulations to unravel stacking order in epitaxially grown bilayer MoS2. Machine learning based data segmentation is employed to obtain useful statistics on grain orientation of monolayer and stacking in bilayer MoS2.

Importance of the substrate's surface evolution during the MOVPE growth of 2D-transition metal dichalcogenides.

In this paper, we explore the impact of changing the growth conditions on the substrate surface during the metal-organic vapor phase epitaxy of 2D-transition metal dichalcogenides. We particularly study the growth of molybdenum disulfide (MoS2) on sapphire substrates at different temperatures. We show that a high temperature leads to a perfect epitaxial alignment of the MoS2 layer with respect to the sapphire substrate underneath, whereas a low temperature growth induces a 30° epitaxial alignment. This behavior is found to be related to the different sapphire top surface re-arrangement under H2S environment at different growth temperatures. Structural analyses conducted on the different samples confirm an improved layer quality at high temperatures. MoS2 channel-based metal-oxide-semiconductor field-effect transistors are fabricated showing improved device performance with channel layers grown at high temperature.

Pituitary germinomas: a multi-institutional study analyzing patient demographics and management patterns.

PURPOSE: Intracranial germinomas are exceedingly rare tumors found in the pineal and suprasellar regions. The extremely low incidence of pituitary germinoma has resulted in a significant gap in knowledge regarding its demographics, management, and treatment outcomes. We present the largest multicenter analysis of pituitary germinomas to date, focused on analyzing demographic and management patterns. METHODS: This study utilizes the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program (2004-2016) to study patients with a primary intracranial germinoma of the pituitary gland. We analyzed demographic information and management strategies among adult and pediatric populations and conducted a 20-year overall survival analysis using Kaplan-Meier curve for a descriptive evaluation of survival outcomes between age groups and treatment groups. RESULTS: 92 patients were included in the study, consisting of 58% pediatric patients and 42% adults, with overall 60% males. 82% patients received radiation as part of the treatment, with no significant difference between pediatric and adult groups. Chemotherapy was used significantly more in pediatrics (p = 0.0002) while surgery was significantly more common in adults (p = 0.0117). The most common treatment in pediatrics was radiation + chemotherapy (47%), while the most common treatment in adults was radiation + gross total resection + chemotherapy (23%) followed by radiation + gross total resection (19%). Younger age, radiotherapy, and chemotherapy were associated with increased 20-year survival on Kaplan-Meier curves. CONCLUSIONS: There exist significant differences in the management of pediatric and adult populations with pituitary germinomas. The low incidence of these tumors makes them challenging to study, but also highlights the importance of national cancer registries in amassing sufficient patient data from which to draw evidence-based conclusions.

Effects of buried grain boundaries in multilayer MoS2.

Two-dimensional transition metal dichalcogenides have been the focus of intense research for their potential application in novel electronic and optoelectronic devices. However, growth of large area two-dimensional transition metal dichalcogenides invariably leads to the formation of grain boundaries that can significantly degrade electrical transport by forming large electrostatic barriers. It is therefore critical to understand their effect on the electronic properties of two-dimensional semiconductors. Using MoS2 as an example material, we are able to probe grain boundaries in top and buried layers using conductive atomic force microscopy. We find that the electrical radius of the grain boundary extends approximately 2 nm from the core into the pristine material. The presence of grain boundaries affects electrical conductivity not just within its own layer, but also in the surrounding layers. Therefore, electrical grain size is always smaller than the physical size, and decreases with increasing thickness of the MoS2. These results signify that the number of layers in synthetically grown 2D materials must ideally be limited for device applications.

Peculiar alignment and strain of 2D WSe2 grown by van der Waals epitaxy on reconstructed sapphire surfaces.

The increasing scientific and industry interest in 2D MX2 materials within the field of nanotechnology has made the single crystalline integration of large area van der Waals (vdW) layers on commercial substrates an important topic. The c-plane oriented (3D crystal) sapphire surface is believed to be an interesting substrate candidate for this challenging 2D/3D integration. Despite the many attempts that have been made, the yet incomplete understanding of vdW epitaxy still results in synthetic material that shows a crystallinity far too low compared to natural crystals that can be exfoliated onto commercial substrates. Thanks to its atomic control and in situ analysis possibilities, molecular beam epitaxy (MBE) offers a potential solution and an appropriate method to enable a more in-depth understanding of this peculiar 2D/3D hetero-epitaxy. Here, we report on how various sapphire surface reconstructions, that are obtained by thermal annealing of the as-received substrates, influence the vdW epitaxy of the MBE-grown WSe2 monolayers (MLs). The surface chemistry and the interatomic arrangement of the reconstructed sapphire surfaces are shown to control the preferential in-plane epitaxial alignment of the stoichiometric WSe2 crystals. In addition, it is demonstrated that the reconstructions also affect the in-plane lattice parameter and thus the in-plane strain of the 2D vdW-bonded MLs. Hence, the results obtained in this work shine more light on the peculiar concept of vdW epitaxy, especially relevant for 2D materials integration on large-scale 3D crystal commercial substrates.

Gunshot wounds to the head: racial disparities in inpatient management and outcomes.

OBJECTIVE: Several studies have indicated that racial disparities may exist in the management and outcomes of acute trauma care. One segment of trauma care that has not been as extensively investigated, however, is that of cranial trauma care. The goal of this study was to determine whether significant differences exist among racial and ethnic groups in various measures of inpatient management and outcomes after gunshot wounds to the head (GWH). METHODS: In this study, the authors used the Nationwide (National) Inpatient Sample (NIS) to investigate all-cause mortality, receipt of surgery, days from admission to initial intervention, discharge disposition, length of hospital stay, and total hospital charges of those with GWH from 2012 to 2016. A 1:1 propensity score-matched analysis was conducted to evaluate the effect of race on these endpoints, while controlling for baseline demographics and comorbidities. RESULTS: A total of 333 patients met the inclusion and exclusion criteria: 148 (44.44%) white/Caucasian, 123 (36.94%) black/African American, 54 (16.22%) Hispanic/Latinx, and 8 (2.40%) Asian. African American patients were sent to immediate care and rehabilitation significantly less often than Caucasian patients (RR 0.17 [95% CI 0.04-0.71]). There were no significant differences in mortality, length of stay, rates of surgical intervention, or total hospital charges among any of the racial groups. CONCLUSIONS: The authors' findings suggest that racial disparities in inpatient cranial trauma care and outcomes may not be as prevalent as previously thought. In fact, the disparities seen were only in disposition. More research is needed to further elucidate and address disparities within this population, particularly those that may exist prior to, and after, hospitalization.

Determining the role of adjuvant radiotherapy in the management of meningioma: a Surveillance, Epidemiology, and End Results analysis.

OBJECTIVEThe aim of this study was to illustrate the demographic characteristics of meningioma patients and observe the effect of adjuvant radiation therapy on survival by using the Surveillance, Epidemiology, and End Results (SEER) database. More specifically, the authors aimed to answer the question of whether adjuvant radiotherapy following resection of atypical meningioma confers a cause-specific survival benefit. Additionally, they attempted to add to previous characterizations of the epidemiology of primary meningiomas and assess the effectiveness of the standard of care for benign and anaplastic meningiomas. They also sought to characterize the efficacy of various treatment options in atypical and anaplastic meningiomas separately since nearly all other analyses have grouped these two together despite varying treatment regimens for these behavior categories.METHODSSEER data from 1973 to 2015 were queried using appropriate ICD-O-3 codes for benign, atypical, and anaplastic meningiomas. Patient demographics, tumor characteristics, and treatment choices were analyzed. The effects of treatment were examined using a multivariate Cox proportional hazards model and Kaplan-Meier survival analysis.RESULTSA total of 57,998 patients were included in the analysis of demographic, meningioma, and treatment characteristics. Among this population, cases of unspecified WHO tumor grade were excluded in the multivariate analysis, leaving a total of 12,931 patients to examine outcomes among treatment paradigms. In benign meningiomas, gross-total resection (HR 0.289, p = 0.013) imparted a significant cause-specific survival benefit over no treatment. In anaplastic meningioma cases, adjuvant radiotherapy imparted a significant survival benefit following both subtotal (HR 0.089, p = 0.018) and gross-total (HR 0.162, p = 0.002) resection as compared to gross-total resection alone. In atypical tumors, gross-total resection plus radiotherapy did not significantly change the hazard risk (HR 1.353, p = 0.628) compared to gross-total resection alone. Similarly, it was found that adjuvant radiation did not significantly benefit survival after a subtotal resection (HR 1.440, p = 0.644).CONCLUSIONSThe results of this study demonstrate that the role of adjuvant radiotherapy, especially after the resection of atypical meningioma, remains somewhat unclear. Thus, given these results, prospective randomized clinical studies are warranted to provide clear information on the effects of adjuvant radiation in meningioma treatment.

Mycobacterium fortuitum Meningitis: Approach to Lumboperitoneal Shunt Infection.

Mycobacterium fortuitum is a rare, opportunistic pathogen most frequently contracted through contact with a contaminated source. An immunocompetent 26-year-old female patient presented to our institution with an infected lumboperitoneal (LP) shunt presenting as continued nonhealing wounds. After multiple debridements, shunt revisions, and wound closure failures, infectious disease specialists were consulted. The wound cultures returned positive for M. fortuitum and the shunt was removed. Cerebrospinal fluid studies revealed significant pleocytosis with normal opening pressure, and the patient was diagnosed as having secondary meningitis. After shunt removal, the patient was treated with intravenous and oral antibiotics, resulting in infection resolution. Five months later, a new LP shunt was placed without infection recurrence. Although M. fortuitum was previously reported in neurosurgical patients with ventriculoperitoneal shunts, which are summarized here, to date this is the first case in the literature of M. fortuitum meningitis from an LP shunt. This case demonstrates the importance of clinicians considering uncommon and slow-growing pathogens, as well as consulting infectious disease specialists for patients with persistent, unexplained infections.

Localized targeted antiangiogenic drug delivery for glioblastoma.

Systemic delivery of antiangiogenic agents has been ineffective in improving the overall survival of patients with both primary and recurrent glioblastoma, in part due to dose-limiting toxicities. With the development of new and efficient localized delivery methods and vehicles, an otherwise lethal dose of antiangiogenic chemotherapy can be used to treat tumors while minimizing systemic side effects. Current in-vitro and in-vivo animal studies have shown promising results that encourage the pursuit towards human clinical trials for localized antiangiogenic treatment in the near future.

Layer-controlled epitaxy of 2D semiconductors: bridging nanoscale phenomena to wafer-scale uniformity.

The rapid cadence of MOSFET scaling is stimulating the development of new technologies and accelerating the introduction of new semiconducting materials as silicon alternative. In this context, 2D materials with a unique layered structure have attracted tremendous interest in recent years, mainly motivated by their ultra-thin body nature and unique optoelectronic and mechanical properties. The development of scalable synthesis techniques is obviously a fundamental step towards the development of a manufacturable technology. Metal-organic chemical vapor deposition has recently been used for the synthesis of large area TMDs, however, an important milestone still needs to be achieved: the ability to precisely control the number of layers and surface uniformity at the nano-to micro-length scale to obtain an atomically flat, self-passivated surface. In this work, we explore various fundamental aspects involved in the chemical vapor deposition process and we provide important insights on the layer-dependence of epitaxial MoS2 film's structural properties. Based on these observations, we propose an original method to achieve a layer-controlled epitaxy of wafer-scale TMDs.