bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Route-choice Strategy on Transit Travel Time Estimates
Authors: Wessel Nate , Farber Steven
Published: April 2019

Estimates of travel time by public transit often rely on the calculation of a shortest-path between two points for a given departure time. Such shortest-paths are time-dependent and not always stable from one moment to the next. Given that actual transit passengers necessarily have imperfect information about the system, their route selection strategies are heuristic and cannot be expected to achieve optimal travel times for all possible departures. Thus an algorithm that returns optimal travel times at all moments will tend to underestimate real travel times all else being equal. While several researchers have noted this issue none have yet measured the extent of the problem. This study observes and measures this effect by contrasting two alternative heuristic routing strategies to a standard shortest-path calculation. The Toronto Transit Commission is used as a case study and we model actual transit operations for the agency over the course of a normal week with archived AVL data transformed into a retrospective GTFS dataset. Travel times are estimated using two alternative route-choice assumptions: 1) habitual selection of the itinerary with the best average travel time and 2) dynamic choice of the next-departing route in a predefined choice set. It is shown that most trips present passengers with a complex choice among competing itineraries and that the choice of itinerary at any given moment of departure may entail substantial travel time risk relative to the optimal outcome. In the context of accessibility modelling, where travel times are typically considered as a distribution, the optimal path method is observed in aggregate to underestimate travel time by about 3-4 minutes at the median and 6-7 minutes at the \nth{90} percentile for a typical trip.
Audits for Accountability: Evidence from Municipal By-Elections in South Africa
Authors: Berliner Daniel , Wehner Joachim
Published: April 2019

Theories of retrospective accountability assume that voters punish poor governance and reward improvements, yet empirical evidence remains mixed. We extend this research to a new context, assessing the impact of audits on electoral outcomes in South African municipalities. Our novel identification strategy focuses on by-elections triggered by deaths in office of local councilors and compares those taking place before and after audit results are announced each year. We find that timely audit information affects the vote share of the responsible party, with voters rewarding improvements and punishing poor audits by about 5 percentage points. Additional individual-level survey evidence confirms the underpinning behavioral response more generally. Our study is the first to demonstrate electoral accountability effects of audit information at full scale, involving universal spatial and temporal coverage as well as public and organic dissemination.
A confusing definition of disruption
Authors: Wu Shijie , Wu Qiang
Published: April 2019

It is important to measure whether a work is disruptive or developing. In 2016, Funk and Owen-Smith proposed novel indexes to evaluate the degree of a patent consolidating or destabilizing the technology streams (doi:10.1287/mnsc.2015.2366). Based on their methods, Wu et al. (2019) studied the disruption of articles, patents and software products, and made a conclusion that small teams are more disruptive than large teams (doi:10.1287/mnsc.2015.2366). Our research finds that the effect of NR on the disruption equation is contradictory as the sign of the disruption changes, and this problem may cause more trouble in any further work based on their indexes. When using other suitable approaches to measure how disruptive a work would be to the field of science or technology, we predict that there is no significant difference between large and small teams.
Prevalence of vitamin D deficiency in patients attending outpatient clinic with thyroid disorders in Chitwan Medical College Teaching Hospital
Authors: Shrestha Bidhan , Adhikari Shital , Piryani Rano Mal , Sedhain Arun , Deep Suresh , Sedhai Sabina , Dhakal Harikrishna
Published: April 2019

Objectives: Vitamin D deficiency is being studied all over the world and is a global health problem. Recent studies haveshown that Vitamin D may have a significant role in reducing the incidence of autoimmune diseases. This study was conducted to find out the level of Vitamin D in patients with thyroid disorders and compare Vitamin D levels in Anti Tpo positive and negative patients.

Subject and Methodology: 60 patients from Chitwan Medical College outpatient clinic were included in the study from February to May 2016. A brief history and clinical examinations were taken from all patients along with laboratory tests for thyroid functions, TPO antibody level of 25(OH) Vitamin D3 level and Serum Calcium level.

Results: Both patients of hypothyroidism (autoimmune and nonautoimmune) had severe Vitamin D deficiency. Most of the hyperthyroid cases had Vitamin D insufficiency. Anti TPO positive and negative patients both had Vitamin D deficiency.

Conclusion: Our study shows there is significant Vitamin D deficiency in hypothyroidism and hyperthyroidism irrespective of its autoimmunity. This study certainly encourages us to screen Vitamin D and supplement Vitamin D to all thyroid disorders patients.
Role of nutraceutical- branched chain amino acids for attenuating skeletal muscle soreness in post exercise status and central fatigue
Authors: Deo Satish Kumar , Pokharel Akritee , Lamichhane Samir , Mudvari Anish
Published: April 2019

Implementation of food extract for target medicinal purpose is a genre in medical science called Nutraceutical which is vast and much of it is yet to be explored. Nowadays general population are aware of the importance of exercise in terms of health benefits but the fatigue and delayed onset muscle soreness (DOMS) are limitations that are to be overcome to continue extensive exercises. For this article, the role of Branched chain amino acids (BCAA) for the purpose is studied from various scientific journal. DOMS is due to direct muscle damage following exercise whereas central fatigue is the sensation of fatigue due to neurochemical changes in brain following exercise. In various studies, DOMS and central fatigue were minimized in terms of duration when given to animals and human volunteers. Further research has to be done regarding dosing regimen of BCAA supplementation and also to uncover any adverse effect of the supplements.
Exfoliative cytology analysis from different sites of the body
Authors: Maharjan Sushana , Ranabhat Sabin , Tiwari Mamata , Bhandari Anita , Osti Bidur Prasad , Neopane Puja
Published: April 2019

Background: Cytological study of body fluids a non-invasive, simple procedure, relatively inexpensive, and helps in faster reporting that has high population acceptance. The present study aims to determine the proportion of malignant and non malignant lesions.

Methods: A total of 1129 specimens of exfoliative cytology were examined during the period over five years from year January 2011 to December 2016 at Department of Pathology at Chitwan Medical College Teaching Hospital, Nepal. The fluid received was centrifuged at 3000 revolutions per minute for five minutes. Smears were made from the sediment. Two to three slides were air dried and stained with Giemsa stain. One slide was immediately fixed in 95% alcohol and stained with Papanicolaou (Pap) stain for cytological evaluation.

Results: Pleural fluid was most common specimen (49.3%) with peritoneal fluid (32%), pericardial fluid (1%), BAL (7.8%), CSF (4%), sputum (3.4%), synovial fluid (2%) and urine (0.5%) specimens. Male to female ratio was 1.33:1. Maximum cases belonged to age group of 50-69 years. Only (5.8%) 67 cases were neoplastic. The maximum cases of malignant neoplasm were detected in pericardial fluid and pleural fluid, each 21 (1.8%) cases, and 20 (1.7%) cases BAL. Malignant effusions were detected in 46 (4%) cases. Maximum malignant cases were adenocarcinoma (71.6%), followed by squamous cell carcinoma (20.8%).

Conclusion: Exfoliative cytology should be suggested in all cases of effusion and suspected malignancies which helps in reaching at a particular diagnosis and aids in further management.
A three-month longitudinal study for diagnostic stability of acute and transient psychotic disorder
Authors: Joshi Devavrat , Adhikari Ananta Prasad , Bhattarai Praveen , Sharma Pawan
Published: April 2019

Background: The diagnostic category of “acute and transient psychotic disorders” (ATPD) comprises of psychotic disorders with features of acute onset (within 2 weeks), presence of typical syndromes that are either polymorphic or schizophrenic or persistently delusional, evidence for associated acute stress and complete recovery in most cases within 2–3 months. Studies of diagnostic stability among patients with the initial diagnosis of ATPD at their first admission have reported modest stabilities spanning over different periods of time, with higher levels of stability reported in samples from the developing countries. This study aimed at investigating the diagnostic stability of cases of ATPD at the Mental Hospital, Lagankhel over a period of 3 months from the first diagnosis.

Methods: ASeventy-five drug naïve patients with the initial diagnosis of first episode ATPD admitted at the in-patient unit of Mental Hospital, Lagankhel were followed up longitudinally and their diagnosis was assessed independently by two consultant psychiatrists over a period of 3 months.

Results: Average age of the sample was 30.71 years. 66.7% of the cases retained their index diagnosis of ATPD at 3 months, while the remaining required diagnostic revision. A higher number of patients had their diagnosis revised to Affective Disorders including Mania and Severe depression with psychotic features (13.88%) when compared to Schizophrenia (6.94%).

Conclusion: ATPD is a relatively stable diagnostic category in the Nepalese Scenario as well with more than two third of the patients retaining the initial diagnosis at 3 months.
Study of association between characteristics of patient and likelihood of benzodiazepine use in psychiatry outpatient department at tertiary care hospital of Kathmandu
Authors: Raut Binod , Khadka Anjan , Manandhar Pradeep , Kandel Kamal
Published: April 2019

Introduction: Benzodiazepines exert their pharmacological properties as hypnotics, anxiolytics, anticonvulsants and muscle relaxants. Benzodiazepines are clinically effective for a number of indication including the reduction of anxiety, the induction and maintenance of sleep, muscle relaxation. They have a range of well documented adverse effects that may outweigh the benefits in certain patient population including psychomotor impairment, development of tolerance and dependence, potential for abuse.

Methods: It is a hospital based prospective cross-sectional study conducted in a psychiatry outpatient department of tertiary care hospital. All the patients attended to the outpatient department of psychiatry and prescribed with benzodiazepine were selected for study. Drug therapy details in medication chart review and clinical review in patients treated with benzodiazepines was analyzed to measure the utilization pattern of benzodiazepines in terms of patient characteristics (e.g. age, gender and marital status), occupation, education and diagnosis, number of prescription of benzodiazepines, their doses, frequency, routes of administration and duration of use in each patient.

Results: Out of a total of 384 patients, 246 of the patients had been currently using at least one benzodiazepine. Prevalence of benzodiazepine use was 64%. There was statistically significant association between benzodiazepines use with gender distribution, occupation and education. The prevalence of benzodiazepines use is relatively higher than that reported in the developed countries. Clonazepam was the most widely used benzodiazepine followed by lorazepam.

Conclusion: The study evaluated the association between characteristics of patient and likelihood of benzodiazepines use. This will definitely help to optimize the drug therapy, improve the quality of care and reduce the negative outcomes in the usage of benzodiazepines.
Current pattern of secondary glaucoma
Authors: Sherpa Dakki , Pokhrel Suprada
Published: April 2019

Objective: To determine the pattern of secondary glaucoma in Nepal Eye Hospital.

Material and Methods: A retrospective hospital based analysis of medical records of patients attending Nepal Eye Hospital Glaucoma clinic over a period of 1 years (Jan 2013 - Jan 2014) was done in order to know the pattern of secondary glaucoma to launch a preventive measure to decrease the burden of glaucoma blindness.

Results: A total of 59 patients with secondary glaucoma were seen during a period of one year. Out of 59 patients of secondary glaucoma 35 (59.28%) were male and 24 (40.66%) were female with male and female ratio to be 1.46:1. Neovascular glaucoma comprised of 52.54%, Lens induced glaucoma 20.34%, Uveitic glaucoma 8.4%, Pseudoexfoliation syndrome 6.75%, Angle recession glaucoma 3.39%, Steroid induced glaucoma 3.39%, Pigmentary glaucoma 1.69%, Pseudophakic glaucoma 1.69% and Glaucomatoiridocyclitic crisis 1.69%. A large number of patients had profound loss of vision and 81.35% patients had presenting visual acuity of less than 3/60.

Conclusion: Secondary glaucoma is a significant problem due to its impact on visual acuity. Identification of etiology of secondary glaucoma along with preventive measures must be undertaken to decrease this burden of blindness in Nepal.
Safety and efficacy of mini-percutaneous nephrolithotomy(PCNL) in renal or upper ureteric stone >1cm
Authors: Khwaunju Pragyan , Tamrakar Kishor Kumar , Sah Keshar Bahadur , Bhattarai Abhishek , Piya Bimochan , Regmi Bharati
Published: April 2019

Abstract available on the PDF.
Surgical management of chronic pancreatitis: a single centre experience
Authors: Bhandari Ramesh Singh , Kafle Brindeswari , Lakhey Paleswan Joshi , Singh Keshav Prasad
Published: April 2019

Abstract available on the PDF.
Appendicectomy profiels at Lumbini Zonal Hospital
Authors: Thapaliya Narad Prasad , Panthi Janardan , Khanal Krishna Prasad , Oli Yam Bahadur
Published: April 2019

Abstract on the PDF.
A clinical audit of newly established intensive care unit in the Far Western Region of Nepal
Authors: Paneru Hem Raj , Sharma Padam Prakash Dev , Kamar Sher Bahadur , Acharya Subhash Prasad , Marhatta Moda Nath
Published: April 2019

Abstract available on the PDF.
Treatment of traumatic dental injuries in dental department: one year study
Authors: Chaudhary Sanjeeb , Gharti Archana , Adhikari Bhawana
Published: April 2019

Abstract available on the PDF.
Goldenhar Syndrome: a case report
Authors: Shrestha Sabin , Paudyal Kanchan Prakash , Yadav Bijendra Kumar
Published: April 2019

Abstract available on the PDF.
Uso de probióticos na avicultura para o controle da Salmonella spp.: revisão de literatura e perspectivas de utilização
Authors: Raposo Ricardo , Ractz Grahl Thays
Published: April 2019

Studies have demonstrated benefits of the use of probiotics in the diet of poultry production, especially in the action against pathogenic microorganisms. This work presents a review on the effects of the use of probiotics on the pathogenic serotypes of Salmonella enterica of birds and a world context on the methods of control of avian salmonellosis. Most of the assays have observed favorable effects, with reduction of colonization through competitive exclusion, decrease of pH, interference in immunological modulation and translocation of the pathogen. Considering the scenario of antimicrobials disuse, probiotics may emerge as one of the main alternatives for the control of this zoonotic agent in poultry commercial productions. However, there is a need for further technical and scientific elucidations as to the viability and applicability of the use of probiotics on a commercial scale.
Dosimetric effects of Onyx embolization on Gamma Knife arteriovenous malformation dose distributions
Authors: Schlesinger David J. , Nordström Håkan , Lundin Anders , Xu Zhiyuan , Sheehan Jason P.
Published: April 2019

OBJECTIVE

Patients with arteriovenous malformations (AVMs) treated with Gamma Knife radiosurgery (GKRS) subsequent to embolization suffer from elevated local failure rates and differences in adverse radiation effects. Onyx is a common embolic material for AVMs. Onyx is formulated with tantalum, a high atomic number (Z = 73) element that has been investigated as a source of dosimetric uncertainty contributing to the less favorable clinical results. However, prior studies have not modeled the complicated anatomical and beam geometries characteristic of GKRS. This study investigated the magnitude of dose perturbation that can occur due to Onyx embolization using clinically realistic anatomical and Gamma Knife beam models.

METHODS

Leksell GammaPlan (LGP) was used to segment the AVM nidus and areas of Onyx from postcontrast stereotactic MRI for 7 patients treated with GKRS postembolization. The resulting contours, skull surface, and clinically selected dose distributions were exported from LGP in DICOM-RT (Digital Imaging and Communications in Medicine–radiotherapy) format. Isocenter locations and dwell times were recorded from the LGP database. Contours were converted into 3D mesh representations using commercial and in-house mesh-editing software. The resulting data were imported into a Monte Carlo (MC) dose calculation engine (Pegasos, Elekta Instruments AB) with a beam geometry for the Gamma Knife Perfexion. The MC-predicted dose distributions were calculated with Onyx assigned manufacturer-reported physical constants (MC-Onyx), and then compared with corresponding distributions in which Onyx was reassigned constants for water (MC-water). Differences in dose metrics were determined, including minimum, maximum, and mean dose to the AVM nidus; selectivity index; and target coverage. Combined differences in dose magnitude and distance to agreement were calculated as 3D Gamma analysis passing rates using tolerance criteria of 0.5%/0.5 mm, 1.0%/1.0 mm, and 3.0%/3.0 mm.

RESULTS

Overall, the mean percentage differences in dose metrics for MC-Onyx relative to MC-water were as follows; all data are reported as mean (SD): minimum dose to AVM = −0.7% (1.4%), mean dose to AVM = 0.1% (0.2%), maximum dose to AVM = 2.9% (5.0%), selectivity = 0.1% (0.2%), and coverage = −0.0% (0.2%). The mean percentage of voxels passing at each Gamma tolerance were as follows: 99.7% (0.1%) for 3.0%/3.0 mm, 98.2% (0.7%) for 1.0%/1.0 mm, and 52.1% (4.4%) for 0.5%/0.5 mm.

CONCLUSIONS

Onyx embolization appears to have a detectable effect on the delivered dose distribution. However, the small changes in dose metrics and high Gamma passing rates at 1.0%/1.0 mm tolerance suggest that these changes are unlikely to be clinically significant. Additional sources of delivery and biological uncertainty should be investigated to determine the root cause of the observed less favorable postembolization GKRS outcomes.
Worldwide variance in the potential utilization of Gamma Knife radiosurgery
Authors: Hamilton Travis , Dade Lunsford L.
Published: April 2019

OBJECTIVE

The role of Gamma Knife radiosurgery (GKRS) has expanded worldwide during the past 3 decades. The authors sought to evaluate whether experienced users vary in their estimate of its potential use.

METHODS

Sixty-six current Gamma Knife users from 24 countries responded to an electronic survey. They estimated the potential role of GKRS for benign and malignant tumors, vascular malformations, and functional disorders. These estimates were compared with published disease epidemiological statistics and the 2014 use reports provided by the Leksell Gamma Knife Society (16,750 cases).

RESULTS

Respondents reported no significant variation in the estimated use in many conditions for which GKRS is performed: meningiomas, vestibular schwannomas, and arteriovenous malformations. Significant variance in the estimated use of GKRS was noted for pituitary tumors, craniopharyngiomas, and cavernous malformations. For many current indications, the authors found significant variance in GKRS users based in the Americas, Europe, and Asia. Experts estimated that GKRS was used in only 8.5% of the 196,000 eligible cases in 2014.

CONCLUSIONS

Although there was a general worldwide consensus regarding many major indications for GKRS, significant variability was noted for several more controversial roles. This expert opinion survey also suggested that GKRS is significantly underutilized for many current diagnoses, especially in the Americas. Future studies should be conducted to investigate health care barriers to GKRS for many patients.
Prognostic value of diffusion tensor imaging parameters for Gamma Knife radiosurgery in meningiomas
Authors: Speckter Herwin , Bido Jose , Hernandez Giancarlo , Mejía Diones Rivera , Suazo Luis , Valenzuela Santiago , Perez-Then Eddy , Stoeter Peter
Published: April 2019

OBJECTIVE

Diffusion tensor imaging (DTI) parameters are able to differentiate between meningioma subtypes. The hypothesis that there is a correlation between DTI parameters and the change in tumor size after Gamma Knife radiosurgery (GKRS) was analyzed.

METHODS

DTI parameters were measured using MRI before GKRS in 26 patients with meningiomas. The findings were correlated with the change in tumor size after treatment as measured at the last follow-up (range 12.5–45 months).

RESULTS

Only those meningiomas that showed the highest fractional anisotropy (FA), the lowest spherical index of the tensor ellipsoid (Cs), and the lowest radial diffusivity (RD) either increased or remained stable in terms of volume, whereas all other meningiomas decreased in volume. The correlation between the DTI parameters (correlation values of −0.81 for FA, 0.75 for Cs, 0.66 for RD, and 0.66 for mean diffusivity) and the rate of volume change per month was significant (p ≤ 0.001). Other factors, including original tumor size, prescription dose, and patient age, did not correlate significantly.

CONCLUSIONS

Meningiomas that show high FA values—as well as low Cs, low RD, and low mean diffusivity values—do not respond as well to GKRS in comparison with meningiomas with low FA values. This finding might be due to their higher content level of fibrous tissue. In particular, the meningioma with the highest FA value (0.444) considerably increased in volume (by 32.3% after 37 months), whereas the meningioma with the lowest FA value (0.151) showed the highest rate of reduction (3.3% per month) in this study.
Cost-effectiveness of stereotactic radiosurgery versus whole-brain radiation therapy for up to 10 brain metastases
Authors: Lester-Coll Nataniel H. , Dosoretz Arie P. , Magnuson William J. , Laurans Maxwell S. , Chiang Veronica L. , Yu James B.
Published: April 2019

OBJECTIVE

The JLGK0901 study found that stereotactic radiosurgery (SRS) is a safe and effective treatment option for treating up to 10 brain metastases. The purpose of this study is to determine the cost-effectiveness of treating up to 10 brain metastases with SRS, whole-brain radiation therapy (WBRT), or SRS and immediate WBRT (SRS+WBRT).

METHODS

A Markov model was developed to evaluate the cost effectiveness of SRS, WBRT, and SRS+WBRT in patients with 1 or 2–10 brain metastases. Transition probabilities were derived from the JLGK0901 study and modified according to the recurrence rates observed in the Radiation Therapy Oncology Group (RTOG) 9508 and European Organization for Research and Treatment of Cancer (EORTC) 22952–26001 studies to simulate the outcomes for patients who receive WBRT. Costs are based on 2015 Medicare reimbursements. Health state utilities were prospectively collected using the Standard Gamble method. End points included cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). The willingness-to-pay (WTP) threshold was $100,000 per QALY. One-way and probabilistic sensitivity analyses explored uncertainty with regard to the model assumptions.

RESULTS

In patients with 1 brain metastasis, the ICERs for SRS versus WBRT, SRS versus SRS+WBRT, and SRS+WBRT versus WBRT were $117,418, $51,348, and $746,997 per QALY gained, respectively. In patients with 2–10 brain metastases, the ICERs were $123,256, $58,903, and $821,042 per QALY gained, respectively. On the sensitivity analyses, the model was sensitive to the cost of SRS and the utilities associated with stable post-SRS and post-WBRT states. In patients with 2–10 brain metastases, SRS versus WBRT becomes cost-effective if the cost of SRS is reduced by $3512. SRS versus WBRT was also cost effective at a WTP of $200,000 per QALY on the probabilistic sensitivity analysis.

CONCLUSIONS

The most cost-effective strategy for patients with up to 10 brain metastases is SRS alone relative to SRS+WBRT. SRS alone may also be cost-effective relative to WBRT alone, but this depends on WTP, the cost of SRS, and patient preferences.
Clinical outcomes in patients with brain metastases from breast cancer treated with single-session radiosurgery or whole brain radiotherapy
Authors: Mix Michael , Elmarzouky Rania , O'Connor Tracey , Plunkett Robert , Prasad Dheerendra
Published: April 2019

OBJECTIVE

Gamma Knife radiosurgery (GKRS) is used to treat brain metastases from breast cancer (BMB) as the sole treatment or in conjunction with tumor resection and/or whole brain radiotherapy (WBRT). This study evaluates outcomes in BMB based on treatment techniques and tumor biological features.

METHODS

The authors reviewed all patients treated with BMB between 2004 and 2014. Patients were identified from a prospectively collected radiosurgery database and institutional tumor registry; 214 patients were identified. Data were collected from aforementioned sources and supplemented with chart review where needed. Independent radiological review was performed for all available brain imaging in those treated with GKRS. Survival analyses are reported using Kaplan-Meier estimates.

RESULTS

During the 10-year study period, 214 patients with BMB were treated; 23% underwent GKRS alone, 46% underwent a combination of GKRS and WBRT, and 31% underwent WBRT alone. Median survival after diagnosis of BMB in those treated with GKRS alone was 21 months, and in those who received WBRT alone it was 3 months. In those treated with GKRS plus WBRT, no significant difference in median survival was observed between those receiving WBRT upfront or in a salvage setting following GKRS (19 months vs 14 months, p = 0.63). The median survival of patients with total metastatic tumor volume of ≤ 7 cm3 versus > 7 cm3 was 20 months vs 7 months (p < 0.001). Human epidermal growth factor receptor-2 (Her-2) positively impacted survival after diagnosis of BMB (19 months vs 12 months, p = 0.03). Estrogen receptor status did not influence survival after diagnosis of BMB. No difference was observed in survival after diagnosis of BMB based on receptor status in those who received WBRT alone.

CONCLUSIONS

In this single-institution series of BMB, the addition of WBRT to GKRS did not significantly influence survival, nor did the number of lesions treated with GKRS. Survival after the diagnosis of BMB was most strongly affected by Her-2 positivity and total metastatic tumor volume.
Results of volume-staged fractionated Gamma Knife radiosurgery for large complex arteriovenous malformations: obliteration rates and clinical outcomes of an evolving treatment paradigm
Authors: Franzin Alberto , Panni Pietro , Spatola Giorgio , Vecchio Antonella del , Gallotti Alberto L. , Gigliotti Carmen R. , Cavalli Andrea , Donofrio Carmine A. , Mortini Pietro
Published: April 2019

OBJECTIVE

There are few reported series regarding volume-staged Gamma Knife radiosurgery (GKRS) for the treatment of large, complex, cerebral arteriovenous malformations (AVMs). The object of this study was to report the results of using volume-staged Gamma Knife radiosurgery for patients affected by large and complex AVMs.

METHODS

Data from 20 patients with large AVMs were prospectively included in the authors' AVM database between 2004 and 2012. A staging strategy was used when treating lesion volumes larger than 10 cm3. Hemorrhage and seizures were the presenting clinical feature for 6 (30%) and 8 (40%) patients, respectively. The median AVM volume was 15.9 cm3 (range 10.1–34.3 cm3). The mean interval between stages (± standard deviation) was 15 months (± 9 months). The median margin dose for each stage was 20 Gy (range 18–25 Gy).

RESULTS

Obliteration was confirmed in 8 (42%) patients after a mean follow-up of 45 months (range 19–87 months). A significant reduction (> 75%) of the original nidal volume was achieved in 4 (20%) patients. Engel Class I–II seizure status was reported by 75% of patients presenting with seizures (50% Engel Class I and 25% Engel Class II) after radiosurgery. After radiosurgery, 71.5% (5/7) of patients who had presented with a worsening neurological deficit reported a complete resolution or amelioration. None of the patients who presented acutely because of hemorrhage experienced a new bleeding episode during follow-up. One (5%) patient developed radionecrosis that caused sensorimotor hemisyndrome. Two (10%) patients sustained a bleeding episode after GKRS, although only 1 (5%) was symptomatic. High nidal flow rate and a time interval between stages of less than 11.7 months were factors significantly associated with AVM obliteration (p = 0.021 and p = 0.041, respectively). Patient age younger than 44 years was significantly associated with a greater than 75% reduction in AVM volume but not with AVM obliteration (p = 0.024).

CONCLUSIONS

According to the results of this study, volume-staged GKRS is an effective and safe treatment strategy for large, complex, cerebral AVMs for which microsurgery or endovascular approaches could carry substantially higher risks to the patient. Radiation doses up to 20 Gy can be safely administered. The time interval between stages should be shorter than 11.7 months to increase the chance of obliteration. High nidal flow and a patient age younger than 44 years were factors associated with nidus obliteration and significant nidus reduction, respectively.
The role of diffusion tensor imaging tractography for Gamma Knife thalamotomy planning
Authors: Gomes João Gabriel Ribeiro , Gorgulho Alessandra Augusta , de Oliveira López Amanda , Saraiva Crystian Wilian Chagas , Damiani Lucas Petri , Pássaro Anderson Martins , Salvajoli João Victor , de Oliveira Siqueira Ludmila , Salvajoli Bernardo Peres , De Salles Antônio Afonso Ferreira
Published: April 2019

OBJECTIVE

The role of tractography in Gamma Knife thalamotomy (GK-T) planning is still unclear. Pyramidal tractography might reduce the risk of radiation injury to the pyramidal tract and reduce motor complications.

METHODS

In this study, the ventralis intermedius nucleus (VIM) targets of 20 patients were bilaterally defined using Iplannet Stereotaxy Software, according to the anterior commissure–posterior commissure (AC-PC) line and considering the localization of the pyramidal tract. The 40 targets and tractography were transferred as objects to the GammaPlan Treatment Planning System (GP-TPS). New targets were defined, according to the AC-PC line in the functional targets section of the GP-TPS. The target offsets required to maintain the internal capsule (IC) constraint of < 15 Gy were evaluated. In addition, the strategies available in GP-TPS to maintain the minimum conventional VIM target dose at > 100 Gy were determined.

RESULTS

A difference was observed between the positions of both targets and the doses to the IC. The lateral (x) and the vertical (z) coordinates were adjusted 1.9 mm medially and 1.3 mm cranially, respectively. The targets defined considering the position of the pyramidal tract were more medial and superior, based on the constraint of 15 Gy touching the object representing the IC in the GP-TPS. The best strategy to meet the set constraints was 90° Gamma angle (GA) with automatic shaping of dose distribution; this was followed by 110° GA. The worst GA was 70°. Treatment time was substantially increased by the shaping strategy, approximately doubling delivery time.

CONCLUSIONS

Routine use of DTI pyramidal tractography might be important to fine-tune GK-T planning. DTI tractography, as well as anisotropy showing the VIM, promises to improve Gamma Knife functional procedures. They allow for a more objective definition of dose constraints to the IC and targeting. DTI pyramidal tractography introduced into the treatment planning may reduce the incidence of motor complications and improve efficacy. This needs to be validated in a large clinical series.
Prognostic factors for melanoma brain metastases treated with stereotactic radiosurgery
Authors: Bian Shelly X. , Routman David , Liu Jonathan , Yang Dongyun , Groshen Susan , Zada Gabriel , Trakul Nicholas , Wong Michael K. , Yu Cheng , Chang Eric L.
Published: April 2019

OBJECTIVE

Stereotactic radiosurgery (SRS) is routinely used to treat brain metastases from melanoma due to their radioresistant nature. The median survival for these patients is 4–6 months, according to earlier studies. The aim of this study was to evaluate prognostic factors that influence survival in patients with metastatic melanoma to the brain treated with SRS.

METHODS

This retrospective analysis included all patients with melanoma brain metastases treated with SRS at the University of Southern California between 1994 and 2015. For the entire cohort, the authors performed a multivariable Cox regression analysis with an end point of survival. Covariates included number of lesions, total intracranial tumor volume, age, sex, and treatment date prior to 2005 or 2005 onward.

In the subset of patients with > 1 lesion, additional multivariable Cox regression was performed, with covariates of Karnofsky Performance Scale, Graded Prognostic Assessment, Recursive Partitioning Analysis, timing of metastases (synchronous/metachronous), change in lesion number, and previous whole-brain radiation therapy or resection in addition to the previously mentioned covariates. Overall survival (OS) was calculated from the day SRS was performed to the date of last follow-up or date of death.

RESULTS

A total of 401 patients were available for analysis. The median follow-up was 35.1 months for patients alive at the time of analysis, and the median OS was 7.7 months for the entire cohort (95% CI 6.7–8.3 months). In the entire cohort, greater number of brain lesions, higher total intracranial tumor volume, age > 50 years, treatment prior to 2005, and male sex were found to be statistically significant factors associated with worse survival. The strongest risk factors for decreased OS were tumor volume > 10 cm3 and ≥ 5 lesions, with hazard ratios for risk of death of 1.7 and 2.2, respectively. In the subset of patients with > 1 lesion, tumor volume > 10 cm3 and no resection were the only factors significantly associated with decreased OS, with hazard ratios of 1.9 and 2.0 (hazard ratio of 0.49 for resection), respectively.

CONCLUSIONS

This study suggests that greater lesion number, higher intracranial tumor volume, older age, treatment prior to 2005, and male sex have prognostic significance for decreased OS in patients with melanoma brain metastases treated with SRS. Additionally, in the subset of patients with > 1 lesion, only higher total tumor volume and no resection were associated with worse survival.
Neurological and neuropsychological outcome after resection of craniopharyngiomas
Authors: Giese Henrik , Haenig Benjamin , Haenig Anna , Unterberg Andreas , Zweckberger Klaus
Published: April 2019

OBJECTIVE

Craniopharyngiomas are rare and benign tumors of the sellar and/or parasellar region. Primary treatment involves resection followed by adjuvant radiotherapy. While the grade of resection was frequently analyzed following surgery, the neurological outcome and especially neuropsychological deficits and quality of life have been neglected for many decades. Therefore, the authors retrospectively analyzed their patient series and prospectively assessed neuropsychological outcome and quality of life following resection of craniopharyngiomas in adults.

METHODS

In total, 71 patients (39 men and 32 women) with a mean age of 49 years were enrolled in the retrospective analysis. In addition, 36 of the 71 patients were included in the prospective arm of the study and underwent neurological and neuropsychological testing as well as quality of life (36-Item Short-Form Health Survey; SF-36) assessment. Factors influencing outcome were identified and correlations calculated.

RESULTS

Resection was performed mostly using a pterional (41.6%, 47/113 surgical procedures) or bifrontal translamina terminalis (30.1%, 34/113 surgical procedures) approach. Following surgery, visual acuity was significantly improved (> 0.2 diopters) in 32.4% (23/71) of patients, or remained stable in 45.1% (32/71) of patients. During long-term follow up, 80.3% (57/71) of patients developed pituitary insufficiency, particularly involving the corticotropic and thyrotrophic axes. In total, 75% (27/36) of patients showed neuropsychological deviations in at least 1 test item. In particular, attentiveness, cognitive speed, and short-term memory were affected. Referring to the SF-36 score, quality of life was affected in both the mental and physical score in 19.4% (7/36) and 33.3% (12/36), respectively. The risk factors that were identified were a tumor volume larger than 9 cm3, tumor extension toward/into the third ventricle or the brainstem, and resection using a bifrontal translamina terminalis or left-sided approach.

CONCLUSIONS

This study demonstrated that resection of craniopharyngiomas is frequently associated with postoperative neuropsychological deficits and hence an impaired quality of life. In addition to tumor size and extension toward/into the third ventricle or the brainstem, selection of the surgical approach may play a crucial role in the patient’s neuropsychological outcome and quality of life.
Effect of glycolysis inhibition by miR-448 on glioma radiosensitivity
Authors: Lan Fengming , Qin Qing , Yu Huiming , Yue Xiao
Published: April 2019

OBJECTIVE

Although glucose metabolism reengineering is a typical feature of various tumors, including glioma, key regulators of glycolytic reprogramming are still poorly understood. The authors sought to investigate whether glycolysis inhibition by microRNA (miR)–448 increases radiosensitivity in glioma cells.

METHODS

The authors used glioma tissue samples from glioma patients, cells from glioblastoma (GBM) cell lines and normal human astrocyte cells, and subcutaneous tumor–bearing U87 cells in mice to examine the effects of signaling regulation by miR-448 in the response of glioma tissues and cells to radiation treatment. Techniques used for investigation included bioinformatics analyses, biochemical assays, luciferase reporter assays, and establishment of subcutaneous tumors in a mouse model. Glucose consumption, LDH activity, and cellular ATP were measured to determine the ability of glioma cells to perform glycolysis. Expression of HIF-1α was measured as a potential target gene of miR-448 in glycolysis.

RESULTS

miR-448 was detected and determined to be significantly downregulated in both glioma tissues from glioma patients and GBM cell lines. Furthermore, miR-448 acted as a tumor-inhibiting factor and suppressed glycolysis in glioma by negatively regulating the activity of HIF-1α signaling and then interfering with its downstream regulators relative to glycolysis, HK1, HK2, and LDHA. Interestingly, overexpression of miR-448 increased the x-radiation sensitivity of glioma cells. Finally, in in vivo experiments, subcutaneous tumor–bearing U87 cells in a mouse model verified that high expression of miR-448 also enhanced glioma radiosensitivity via inhibiting glycolytic factors.

CONCLUSIONS

miR-448 can promote radiosensitivity by inhibiting HIF-1α signaling and then negatively controlling the glycolysis process in glioma. A newly identified miR-448–HIF-1α axis acts as a potentially valuable therapeutic target that may be useful in overcoming radioresistance in glioma treatment.
Full tractography for detecting the position of cranial nerves in preoperative planning for skull base surgery: technical note
Authors: Jacquesson Timothee , Yeh Fang-Chang , Panesar Sandip , Barrios Jessica , Attyé Arnaud , Frindel Carole , Cotton Francois , Gardner Paul , Jouanneau Emmanuel , Fernandez-Miranda Juan C.
Published: April 2019

OBJECTIVE

Diffusion imaging tractography has allowed the in vivo description of brain white matter. One of its applications is preoperative planning for brain tumor resection. Due to a limited spatial and angular resolution, it is difficult for fiber tracking to delineate fiber crossing areas and small-scale structures, in particular brainstem tracts and cranial nerves. New methods are being developed but these involve extensive multistep tractography pipelines including the patient-specific design of multiple regions of interest (ROIs). The authors propose a new practical full tractography method that could be implemented in routine presurgical planning for skull base surgery.

METHODS

A Philips MRI machine provided diffusion-weighted and anatomical sequences for 2 healthy volunteers and 2 skull base tumor patients. Tractography of the full brainstem, the cerebellum, and cranial nerves was performed using the software DSI Studio, generalized-q-sampling reconstruction, orientation distribution function (ODF) of fibers, and a quantitative anisotropy–based generalized deterministic algorithm. No ROI or extensive manual filtering of spurious fibers was used. Tractography rendering was displayed in a tridimensional space with directional color code. This approach was also tested on diffusion data from the Human Connectome Project (HCP) database.

RESULTS

The brainstem, the cerebellum, and the cisternal segments of most cranial nerves were depicted in all participants. In cases of skull base tumors, the tridimensional rendering permitted the visualization of the whole anatomical environment and cranial nerve displacement, thus helping the surgical strategy.

CONCLUSIONS

As opposed to classical ROI-based methods, this novel full tractography approach could enable routine enhanced surgical planning or brain imaging for skull base tumors.
The post-aSAH syndrome: a self-reported cluster of symptoms in patients with aneurysmal subarachnoid hemorrhage
Authors: Haug Nordenmark Tonje , Karic Tanja , Røe Cecilie , Sorteberg Wilhelm , Sorteberg Angelika
Published: April 2019

OBJECTIVE

Although many patients recover to a good functional outcome after aneurysmal subarachnoid hemorrhage (aSAH), residual symptoms are very common and may have a large impact on the patient’s daily life. The particular cluster of residual symptoms after aSAH has not previously been described in detail and there is no validated questionnaire that covers the typical problems reported after aSAH. Many of the symptoms are similar to post-concussion syndrome, which often is evaluated with the Rivermead Post-Concussion Symptoms Questionnaire (RPQ). In the present study, the authors therefore performed an exploratory use of the RPQ as a template to describe post-aSAH syndrome.

METHODS

The RPQ was administered to 128 patients in the chronic phase after aSAH along with a battery of quality-of-life questionnaires. The patients also underwent a medical examination besides cognitive and physical testing. Based on their RPQ scores, patients were dichotomized into a “syndrome” group or “recovery” group.

RESULTS

A post-aSAH syndrome was seen in 33% of the patients and their symptom burden on all RPQ subscales was significantly higher than that of patients who had recovered on all RPQ subscales. The symptom cluster consisted mainly of fatigue, cognitive problems, and emotional problems. Physical problems were less frequently reported. Patients with post-aSAH syndrome scored significantly worse on mobility and pain scores, as well as on quality-of-life questionnaires. They also had significantly poorer scores on neuropsychological tests of verbal learning, verbal short- and long-term memory, psychomotor speed, and executive functions. Whereas 36% of the patients in the recovery group were able to return to their premorbid occupational status, this was true for only 1 patient in the syndrome group.

CONCLUSIONS

Approximately one-third of aSAH patients develop a post-aSAH syndrome. These patients struggle with fatigue and cognitive and emotional problems. Patients with post-aSAH syndrome report more pain and reduced quality of life compared to patients without this cluster of residual symptoms and have larger cognitive deficits. In this sample, patients with post-aSAH syndrome were almost invariably excluded from return to work. The RPQ is a simple questionnaire covering the specter of residual symptoms after aSAH. Being able to acknowledge these patients’ complaints as a defined syndrome using the RPQ should help patients to accept and cope, thereby alleviating possible secondary distress produced.
Validation of a freehand technique for cortical bone trajectory screws in the lumbar spine
Authors: Tan Zachary , McLachlin Stewart , Whyne Cari , Finkelstein Joel
Published: April 2019

OBJECTIVE

The cortical bone trajectory (CBT) technique for pedicle screw placement has gained popularity among spinal surgeons. It has been shown biomechanically to provide better fixation and improved pullout strength compared to a traditional pedicle screw trajectory. The CBT technique also allows for a less invasive approach for fusion and may have lower incidence of adjacent-level disease. A limitation of the current CBT technique is a lack of readily identifiable and reproducible visual landmarks to guide freehand CBT screw placement in comparison to the well-defined identifiable landmarks for traditional pedicle screw insertion. The goal of this study was to validate a safe and intuitive freehand technique for placement of CBT screws based on optimization of virtual CBT screw placement using anatomical landmarks in the lumbar spine. The authors hypothesized that virtual identification of anatomical landmarks on 3D models of the lumbar spine generated from CT scans would translate to a safe intraoperative freehand technique.

METHODS

Customized, open-source medical imaging and visualization software (3D Slicer) was used in this study to develop a workflow for virtual simulation of lumbar CBT screw insertion. First, in an ex vivo study, 20 anonymous CT image series of normal and degenerative lumbar spines and virtual screw insertion were conducted to place CBT screws bilaterally in the L1–5 vertebrae for each image volume. The optimal safe CBT trajectory was created by maximizing both the screw length and the cortical bone contact with the screw. Easily identifiable anatomical surface landmarks for the start point and trajectory that best allowed the reproducible idealized screw position were determined. An in vivo validation of the determined landmarks from the ex vivo study was then performed in 10 patients. Placement of virtual “test” cortical bone trajectory screws was simulated with the surgeon blinded to the real-time image-guided navigation, and the placement was evaluated. The surgeon then placed the definitive screw using image guidance.

RESULTS

From the ex vivo study, the optimized technique and landmarks were similar in the L1–4 vertebrae, whereas the L5 optimized technique was distinct. The in vivo validation yielded ideal, safe, and unsafe screws in 62%, 16%, and 22% of cases, respectively. A common reason for the nonidealized trajectories was the obscuration of patient anatomy secondary to severe degenerative changes.

CONCLUSIONS

CBT screws were placed ideally or safely 78% of the time in a virtual simulation model. A 22% rate of unsafe freehand trajectories suggests that the CBT technique requires use of image-guided navigation or x-ray guidance and that reliable freehand CBT screw insertion based on anatomical landmarks is not reliably feasible in the lumbar spine.