Neuronavigation-Specific Parameters for Selective Access of Trigeminal Rootlets in Radiofrequency Lesioning: A Cadaveric Morphometric Study.

BACKGROUND AND OBJECTIVE: Radiofrequency lesioning (RFL) is a safe and effective treatment for medically refractory trigeminal neuralgia. Despite gaining mainstream neurosurgical acceptance in the 1970s, the technique has remained relatively unchanged, with the majority of series using lateral fluoroscopy over neuronavigation for cannula guidance. To date, there are no studies describing neuronavigation-specific parameters to help neurosurgeons selectively target individual trigeminal rootlets. In this cadaveric study, we sought to provide a neuronavigation-specific morphometric roadmap for selective targeting of individual trigeminal rootlets. METHODS: Embalmed cadaveric specimens were registered to cranial neuronavigation. Frontotemporal craniotomies were then performed to facilitate direct visualization of the Gasserian ganglion. A 19-gauge cannula was retrofit to a navigation probe, permitting real-time tracking. Using preplanned trajectories, the cannula was advanced through foramen ovale (FO) to the navigated posterior clival line (nPCL). A curved electrode was inserted to the nPCL and oriented inferolaterally for V3 and superomedially for V2. For V1, the cannula was advanced 5 mm distal to the nPCL and the curved electrode was reoriented inferomedially. A surgical microscope was used to determine successful contact. Morphometric data from the neuronavigation unit were recorded. RESULTS: Twenty RFL procedures were performed (10R, 10L). Successful contact with V3, V2, and V1 was made in 95%, 90%, and 85% of attempts, respectively. Mean distances from the entry point to FO and from FO to the clival line were 7.61 cm and 1.26 cm, respectively. CONCLUSION: In this proof-of-concept study, we found that reliable access to V1-3 could be obtained with the neuronavigation-specific algorithm described above. Neuronavigation for RFL warrants further investigation as a potential tool to improve anatomic selectivity, operative efficiency, and ultimately patient outcomes.

Low Skeletal Muscle as a Risk Factor for Worse Survival in Nonmetastatic Renal Cell Carcinoma with Venous Tumor Thrombus.

BACKGROUND: Renal cell carcinoma (RCC) with tumor thrombosis often requires nephrectomy and tumor thrombectomy. As an extensive and potentially morbid operation, patient preoperative functional reserve and body composition is an important consideration. Sarcopenia is a risk factor for increased postoperative complications, systemic therapy toxicity, and death solid organ tumors, including RCC. The influence of sarcopenia in RCC patients with tumor thrombus is not well defined. This study evaluates the prognostic ability of sarcopenia regarding surgical outcomes and complications in patients undergoing surgery for RCC with tumor thrombus. METHODS: We retrospectively analyzed patients with nonmetastatic RCC and tumor thrombus undergoing radical nephrectomy and tumor thrombectomy. Skeletal muscle index (SMI; cm2/m2) was measured on preoperative CT/MRI. Sarcopenia was defined using body mass index- and sex-stratified thresholds optimally fit via a receiver-operating characteristic analysis for survival. Associations between preoperative sarcopenia and overall (OS), cancer-specific survival (CSS), and 90-day major complications were determined using multivariable analysis. RESULTS: 115 patients were analyzed, with median (IQR) age and body mass index of 69 (56-72) and 28.6 kg/m2 (23.6-32.9), respectively. 96 (83.4%) of the cohort had ccRCC. Sarcopenia was associated with shorter median OS (P = .0017) and CSS (P = .0019) in Kaplan-Meier analysis. In multivariable analysis, preoperative sarcopenia was prognostic of shorter OS (HR = 3.38, 95% confidence interval [CI] 1.61-7.09) and CSS (HR = 5.15, 95% CI 1.46-18.18). Notably, 1 unit increases in SMI were associated with improved OS (HR = 0.97, 95% CI 0.94-0.999) but not CSS (HR = 0.95, 95% CI 0.90-1.01). No significant relationship between preoperative sarcopenia and 90-day major surgical complications was observed in this cohort (HR = 2.04, 95% CI 0.65-6.42). CONCLUSION: Preoperative sarcopenia was associated with decreased OS and CSS in patients surgically managed for nonmetastatic RCC and VTT, however, was not predictive of 90-day major postoperative complications. Body composition analysis has prognostic utility for patients with nonmetastatic RCC and venous tumor thrombus undergoing surgery.

Novel System of Simulation Models for Aneurysm Clipping Training: Description of Models and Assessment of Face, Content, and Construct Validity.

BACKGROUND: Aneurysm clipping simulation models are needed to provide tactile feedback of biological vessels in a nonhazardous but surgically relevant environment. OBJECTIVE: To describe a novel system of simulation models for aneurysm clipping training and assess its validity. METHODS: Craniotomy models were fabricated to mimic actual tissues and movement restrictions experienced during actual surgery. Turkey wing vessels were used to create aneurysm models with patient-specific geometry. Three simulation models (middle cerebral artery aneurysm clipping via a pterional approach, anterior cerebral artery aneurysm clipping via an interhemispheric approach, and basilar artery aneurysm clipping via an orbitozygomatic pretemporal approach) were subjected to face, content, and construct validity assessments by experienced neurosurgeons (n = 8) and neurosurgery trainees (n = 8). RESULTS: Most participants scored the model as replicating actual aneurysm clipping well and scored the difficulty of clipping as being comparable to that of real surgery, confirming face validity. Most participants responded that the model could improve clip-applier-handling skills when working with patients, which confirms content validity. Experienced neurosurgeons performed significantly better than trainees on all 3 models based on subjective (P = .003) and objective (P < .01) ratings and on time to complete the task (P = .04), which confirms construct validity. Simulations were used to discuss clip application strategies and compare them to prototype clinical cases. CONCLUSION: This novel aneurysm clipping model can be used safely outside the wet laboratory; it has high face, content, and construct validity; and it can be an effective training tool for microneurosurgery training during aneurysm surgery courses.

Hospital use following anterior cervical discectomy and fusion.

Most existing anterior cervical discectomy and fusion (ACDF) outcome studies omit emergency department (ED) use. To our knowledge, this study on ED use following ACDF surgery is the first to use a direct patient chart review and the first to include revision patients, 1-5 levels of ACDFs, and performance of corpectomy in the analysis. This study examines the frequency and basis of hospital service use within 30 days of ACDF surgery, specifically ED visits, hospital readmissions, and returns to the operating room. A retrospective chart review was performed for 1273 consecutive patients who underwent ACDF surgery at one institution from July 2013 to June 2016. Of the 1273 patients with ACDF, 97 (7.6%) presented to the ED within 30 days after surgery. Of 43 patients with revision ACDF, 9 (20.9%) returned to the ED, compared with 88 (7.2%) of 1230 patients with primary ACDF (P = 0.001). Of the 111 ED visits by 97 patients, 40 (36%) were for cervicalgia, 13 (12%) were for dysphagia, 8 (7%) were for trauma, 7 (6%) were for nausea, 4 (4%) were for medication refill, 3 (3%) were for dehiscence, 3 (3%) were for pneumonia, and 3 (3%) were for urinary tract infection. Of the ED presentations, 8 (7%) occurred during the first 2 days after surgery, and 46 (41%) occurred within the first postoperative week.

Postoperative 30-day emergency department utilization after 7294 cranial neurosurgery procedures at a tertiary neuroscience center.

OBJECTIVE: Hospital readmission and the reduction thereof has become a major quality improvement initiative in organized medicine and neurosurgery. However, little research has been performed on why neurosurgical patients utilize hospital emergency rooms (ERs) with or without subsequent admission in the postoperative setting. METHODS: This study was a retrospective, single-center review of data for all surgical cranial procedures performed from July 2013 to July 2016 in patients who survived to discharge. The study was approved by the institutional review board of the participating medical center. RESULTS: The authors identified 7294 cranial procedures performed during 6596 hospital encounters in 5385 patients. The rate of postoperative ER utilization within 30 days after surgical hospitalization across all procedure types was 13.1 per 100 surgeries performed. The two most common chief complaints were pain (30.7%) and medical complication (18.2%). After identification of relevant surgical and patient factors with univariable analysis, a multivariable backward elimination logistic regression model was constructed in which Ommaya reservoir placement (OR 2.65, p = 0.0008) and cranial CSF shunt placement (OR 1.40, p = 0.0001) were associated with increased ER utilization. Deep brain stimulation electrode placement (OR 0.488, p = 0.0004), increasing hospital length of stay (OR 0.935, p < 0.0001), and increasing patient age (OR 0.988, p < 0.0001) were associated with lower rates of postoperative ER utilization. One-half (50%) of ER visit patients were readmitted to the hospital. New/worsening neurological deficit chief complaint (OR 1.99, p = 0.0088), fever chief complaint (OR 2.41, p = 0.0205), altered mentation chief complaint (OR 2.71, p = 0.0002), patient chronic kidney disease (OR 3.31, p = 0.0037), brain biopsy procedure type (OR 3.50, p = 0.0398), and wound infection chief complaint (OR 31.4, p = 0.0008) were associated with increased rates of readmission to the hospital from the ER in multivariable analysis. CONCLUSIONS: The authors report the rates of and reasons for ER utilization in a large cohort of postoperative cranial neurosurgical patients. Factors identified were associated with both increased and decreased use of the ER after cranial surgery, as well as variables associated with readmission to the hospital after postoperative ER visitation. These findings may direct future quality improvement via prospective implementation of care pathways for high-risk procedures.

Posterior interhemispheric occipital transtentorial approach for resection of a falcotentorial meningioma.

Falcotentorial meningiomas arise along the junction of the falx cerebri and the tentorium cerebelli. The authors present a woman in her 60s with an incidentally discovered falcotentorial meningioma, approximately 3 cm in diameter, resected with a torcular craniotomy and posterior interhemispheric approach. The galenic complex was dissected away from the tumor. In the final view, the bilateral internal cerebral veins and basal veins of Rosenthal were seen. A Simpson grade I resection was achieved. The patient experienced transient contralateral hemianopsia and was discharged home. At 1-year follow-up, her neurological examination findings were unremarkable, and there was no radiographic evidence of tumor. The video can be found here: https://stream.cadmore.media/r10.3171/2021.4.FOCVID2125.

Neurosurgical Management of Cancer Facial Pain.

Facial pain occurs in approximately 80% of patients with head and neck cancers. Pain in these settings may result directly from the tumor, or indirectly as a side effect of oncological treatment of the tumor. Optimizing treatment for cancer pain of the face, therefore, involves a variety of diagnostic and treatment considerations, with the development of a successful treatment algorithm dependent on accurate diagnosis of the anatomical location of the pain, its relationship to the facial pain pathway, the type of pain being treated and, finally, patient's prognosis and preference for treatment modality. Beyond direct treatments to reduce tumor burden, a wide variety of neuro-ablative and neuro-augmentative approaches are available that may be tailored to a patient's specific pain syndrome and individual clinical context, taking into account the patient's treatment goals, life expectancy, other cancer-related medical problems, and end-of-life issues.

Laparoscopic-Assisted Ventriculoperitoneal Shunt Placement and Reduction in Operative Time and Total Hospital Charges.

OBJECTIVE: In ventriculoperitoneal shunt (VPS) placement, distal placement of the peritoneal catheter will typically be performed by a neurosurgeon. More recently, laparoscopic-assisted (LA) placement of the distal peritoneal catheter by general surgeons has become common. The present study examined whether LA placement of a VPS (LAVPS) is associated with a reduced operative time, lower hospital costs, and fewer distal revisions. METHODS: A retrospective review was performed of the data from all patients who had received a new VPS at our institution from 2013 to 2016. Age, sex, diagnosis, previous abdominal surgery, operative time, anesthesia grade, incidence of 30-day shunt failure, and total hospital charges were analyzed. RESULTS: A total of 680 patients had undergone first-time VPS placement, including 199 with LAVPS and 481 with non-LAVPS placement (non-LAVPS). The mean age of the LAVPS patients was significantly older than that of the non-LAVPS patients (64.1 vs. 59.3 years; P = 0.002). The mean operative time was shorter in the LAVPS group than in the non-LAVPS group (55 vs. 75 minutes; P < 0.001). Distal shunt revision within 30 days occurred more often for the non-LAVPS patients (6 of 481 [1.2%]) than for the LAVPS patients (0 of 199 [0%]). A subset analysis of patients with normal-pressure hydrocephalus found decreased total hospital charges in the LAVPS group ($67,124 vs. $80,890; P = 0.009). CONCLUSIONS: Compared with non-LAVPS, LAVPS was associated with significantly shorter operative times and fewer distal shunt revisions within 30 days. The findings from a subset analysis supported a decrease in total hospital charges. Additional studies are needed; however, these data suggest that LAVPS is a safer, less-expensive alternative to non-LAVPS.

Accuracy in Deep Brain Stimulation Electrode Placement: A Single-Surgeon Retrospective Analysis of Sterotactic Error in Overlapping and Non-Overlapping Surgical Cases.

BACKGROUND: Many surgeons utilize assistants to perform procedures in more than one operating room at a given time using a practice known as overlapping surgery. Debate has continued as to whether overlapping surgery improves the efficiency and access to care or risks patient safety and outcomes. OBJECTIVE: To examine effects of overlapping surgery in deep brain stimulation (DBS) for movement disorders. METHODS: In this retrospective analysis of overlapping and non-overlapping cases, we evaluated stereotactic accuracy, operative duration, length of hospital stay, and the presence of hemorrhage, wound-related complications, and hardware-related complications requiring revision in adults with movement disorders undergoing DBS. RESULTS: Of 324 cases, 141 (43.5%) were overlapping and 183 (56.5%) non-overlapping. Stereotactic error, number of brain penetrations, and postoperative length of hospitalization did not differ significantly (p ≥ 0.08) between the overlapping and non-overlapping groups. Mean operative duration was significantly longer for overlapping (81/141 [57.4%], 189.5 ± 10.8 min) than for non-overlapping cases (79/183 [43.2%], 169.9 ± 7.6 min; p = 0.004). There were no differences in rates of wound-related complications or hemorrhages, but overlapping cases had a significantly higher rate of hardware-related complications requiring revision (7/141 [5.0%] vs. 0/183 [0%]; p = 0.002). CONCLUSIONS: Overlapping and non-overlapping cases had comparable DBS lead placement accuracy. Overlapping cases had a longer operative duration and had a higher rate of hardware-related complications requiring revision.

Proposal and Validation of a Simple Grading Scale (TRANSSPHER Grade) for Predicting Gross Total Resection of Nonfunctioning Pituitary Macroadenomas After Transsphenoidal Surgery.

BACKGROUND: A simple, reliable grading scale to better characterize nonfunctioning pituitary adenomas (NFPAs) preoperatively has potential for research and clinical applications. OBJECTIVE: To develop a grading scale from a prospective multicenter cohort of patients that accurately and reliably predicts the likelihood of gross total resection (GTR) after transsphenoidal NFPA surgery. METHODS: Extent-of-resection (EOR) data from a prospective multicenter study in transsphenoidal NFPA surgery were analyzed (TRANSSPHER study; ClinicalTrials.gov NCT02357498). Sixteen preoperative radiographic magnetic resonance imaging (MRI) tumor characteristics (eg, tumor size, invasion measures, tumor signal characteristics, and parameters impacting surgical access) were evaluated to determine EOR predictors, to calculate receiver-operating characteristic curves, and to develop a grading scale. A separate validation cohort (n = 165) was examined to assess the scale's performance and inter-rater reliability. RESULTS: Data for 222 patients from 7 centers treated by 15 surgeons were analyzed. Approximately one-fifth of patients (18.5%; 41 of 222) underwent subtotal resection (STR). Maximum tumor diameter > 40 mm; nodular tumor extension through the diaphragma into the frontal lobe, temporal lobe, posterior fossa, or ventricle; and Knosp grades 3 to 4 were identified as independent STR predictors. A grading scale (TRANSSPHER grade) based on a combination of these 3 features outperformed individual variables in predicting GTR (AUC, 0.732). In a validation cohort, the scale exhibited high sensitivity and specificity (AUC, 0.779) and strong inter-rater reliability (kappa coefficient, 0.617). CONCLUSION: This simple, reliable grading scale based on preoperative MRI characteristics can be used to better characterize NFPAs for clinical and research purposes and to predict the likelihood of achieving GTR.

Cost Transparency in Neurosurgery: A Single-Institution Analysis of Patient Out-of-Pocket Spending in 13 673 Consecutive Neurosurgery Cases.

BACKGROUND: Patient out-of-pocket (OOP) spending is an increasingly discussed topic; however, there is minimal data available on the patient financial burden of surgical procedures. OBJECTIVE: To analyze hospital and surgeon expected payment data and patient OOP spending in neurosurgery. METHODS: This is a retrospective cohort study of neurosurgical patients at a tertiary-referral center from 2013 to 2016. Expected payments, reflecting negotiated costs-of-care, as well as actual patient OOP payments for hospital care and surgeon professional fees were analyzed. A 4-tiered model of patient OOP cost sharing and a multivariate model of patient expected payments were created. RESULTS: A total of 13 673 consecutive neurosurgical cases were analyzed. Patient age, insurance type, case category, severity of illness, length of stay (LOS), and elective case status were significant predictors of increased expected payments (P < .05). Craniotomy ($53 397 ± 811) and posterior spinal fusion ($48 329 ± 864) were associated with the highest expected payments. In a model of patient OOP cost sharing, nearly all neurosurgical procedures exceeded yearly OOP maximums for Healthcare Marketplace plans. Mean patient payments for hospital care and surgeon professional fees were the highest for anterior/lateral spinal fusion cases for commercially insured patients ($1662 ± 165). Mean expected payments and mean patient payments for commercially insured patients increased significantly from 2013 to 2016 (P < .05). CONCLUSION: Expected payments and patient OOP spending for commercially insured patients significantly increased from 2013 to 2016, representing increased healthcare costs and patient cost sharing in an evolving healthcare environment. Patients and providers can consider this information prior to surgery to better anticipate the individual financial burden for neurosurgical care.

The Barrow Innovation Center: A Novel Program in Neurosurgery Resident Education and Medical Device Innovation.

Medical innovation is the application of scientific knowledge and problem solving for the betterment of the human condition. Every great advancement in the field of neurosurgery can be traced back to a novel surgical procedure or technology that challenged existing standards of care. Considering the critical importance of innovation to the advancement of neurosurgery, and a surprising lack of formal training in innovation among residency programs, we sought to create a residency training program in neurosurgical innovation. Neurosurgery residents at the authors' institution envisioned the creation of a program that contained all the necessary equipment, personnel, and information required to bring their ideas from theoretical concepts to functional devices implemented in a clinical setting. The Barrow Innovation Center was established as a result. The center currently comprises a rapid prototyping laboratory and several collaborative partnerships between neurosurgery residents, patent law students, and biomedical engineering students. The creation of this model was guided by an overarching mission to educate the next generation of neurosurgical innovators. With modest start-up capital and strong faculty and institutional support, the center has grown from a simple idea to a multistate, multidisciplinary collaboration in just 18 months; it has generated substantial intellectual property, educational opportunities, and a new business entity. We hope that by continuing to advance the Barrow Innovation Center and its core mission of innovation education, we will advance the field of neurosurgery by providing the next generation of surgeon-scientists with the skills, knowledge, and opportunity needed to revolutionize the field.

Patient out-of-pocket spending in cranial neurosurgery: single-institution analysis of 6569 consecutive cases and literature review.

OBJECTIVE With drastic changes to the health insurance market, patient cost sharing has significantly increased in recent years. However, the patient financial burden, or out-of-pocket (OOP) costs, for surgical procedures is poorly understood. The goal of this study was to analyze patient OOP spending in cranial neurosurgery and identify drivers of OOP spending growth. METHODS For 6569 consecutive patients who underwent cranial neurosurgery from 2013 to 2016 at the authors' institution, the authors created univariate and multivariate mixed-effects models to investigate the effect of patient demographic and clinical factors on patient OOP spending. The authors examined OOP payments stratified into 10 subsets of case categories and created a generalized linear model to study the growth of OOP spending over time. RESULTS In the multivariate model, case categories (craniotomy for pain, tumor, and vascular lesions), commercial insurance, and out-of-network plans were significant predictors of higher OOP payments for patients (all p < 0.05). Patient spending varied substantially across procedure types, with patients undergoing craniotomy for pain ($1151 ± $209) having the highest mean OOP payments. On average, commercially insured patients spent nearly twice as much in OOP payments as the overall population. From 2013 to 2016, the mean patient OOP spending increased 17%, from $598 to $698 per patient encounter. Commercially insured patients experienced more significant growth in OOP spending, with a cumulative rate of growth of 42% ($991 in 2013 to $1403 in 2016). CONCLUSIONS Even after controlling for inflation, case-mix differences, and partial fiscal periods, OOP spending for cranial neurosurgery patients significantly increased from 2013 to 2016. The mean OOP spending for commercially insured neurosurgical patients exceeded $1400 in 2016, with an average annual growth rate of 13%. As patient cost sharing in health insurance plans becomes more prevalent, patients and providers must consider the potential financial burden for patients receiving specialized neurosurgical care.

Analysis of overlapping surgery in patients undergoing microsurgical aneurysm clipping: acute and long-term outcomes from the Barrow Ruptured Aneurysm Trial.

OBJECTIVE Overlapping surgery is a controversial subject in medicine today; however, few studies have examined the outcomes of this practice. The authors analyzed outcomes of patients with acutely ruptured saccular aneurysms who were treated with microsurgical clipping in a prospectively collected database from the Barrow Ruptured Aneurysm Trial. Acute and long-term outcomes for overlapping versus nonoverlapping cases were compared. METHODS During the study period, 241 patients with ruptured saccular aneurysms underwent microsurgical clipping. Patients were separated into overlapping (n = 123) and nonoverlapping (n = 118) groups based on surgical start/stop times. Outcomes at discharge and at 6 months, 1 year, 3 years, and 6 years after surgery were analyzed. RESULTS Patient variables (e.g., age, smoking status, cardiovascular history, Hunt and Hess grade, Fisher grade, and aneurysm size) were similar between the 2 groups. Aneurysm locations were similar, with the exception of the overlapping group having more posterior circulation aneurysms (18/123 [15%]) than the nonoverlapping group (8/118 [7%]) (p = 0.0495). Confirmed aneurysm obliteration at discharge was significantly higher for the overlapping group (109/119 [91.6%]) than for the nonoverlapping group (95/116 [81.9%]) (p = 0.03). Hospital length of stay, discharge location, and proportions of patients with a modified Rankin Scale (mRS) score > 2 at discharge and up to 6 years postoperatively were similar. The mean and median mRS, Glasgow Outcome Scale, Mini-Mental State Examination, National Institutes of Health Stroke Scale, and Barthel Index scores at all time points were not statistically different between the groups. CONCLUSIONS Compared with nonoverlapping surgery, overlapping surgery was not associated with worse outcomes for any variable at any time point, despite the complexity of the surgical management in this patient population. These findings should be considered during the discussion of future guidelines on the practice of overlapping surgery.

Overlapping Surgeries Are Not Associated With Worse Patient Outcomes: Retrospective Multivariate Analysis of 14 872 Neurosurgical Cases Performed at a Single Institution.

BACKGROUND: Overlapping surgeries have recently become a controversial topic. OBJECTIVE: To evaluate the effect of overlapping surgeries on patient outcomes. METHODS: A retrospective analysis of all neurosurgical procedures performed at a single institution from July 2013 to May 2016 was conducted. Variables extracted from the electronic medical records included sex, age, procedure type, resident years of training, evening case, emergency case, American Society of Anesthesiologists Physical Status Score, illness severity, mortality risk, and percentage of case overlap. Univariate and multivariate analyses were performed for the following primary outcomes: procedure length, length of hospital stay, return to operating room (OR), disposition upon discharge, hospital readmission, and mortality. Separate analyses were performed for overlap thresholds of 0%, 20%, 50%, and 100%. RESULTS: A total of 14 872 cases were performed during the study period, and all were included in the statistical analyses. Univariate analysis showed a benefit for overlapping surgeries in terms of hospital length of stay, return to OR, and disposition status (all P < .001). No difference was found for hospital readmission or mortality. Overlapping surgeries were significantly longer and were staffed by more senior residents (P < .001). Multivariate analysis showed a benefit for overlapping surgeries, or no difference, for all the measured outcomes except procedure length. CONCLUSION: These results reject the hypothesis that overlapping surgeries are predictive of worse outcomes. When considered in the context of the current debate regarding overlapping surgeries, these results argue against claims that overlapping surgeries are dangerous or harmful to patients.

Increasing Leaf Vein Density via Mutagenesis in Rice Results in an Enhanced Rate of Photosynthesis, Smaller Cell Sizes and Can Reduce Interveinal Mesophyll Cell Number.

Improvements to leaf photosynthetic rates of crops can be achieved by targeted manipulation of individual component processes, such as the activity and properties of RuBisCO or photoprotection. This study shows that simple forward genetic screens of mutant populations can also be used to rapidly generate photosynthesis variants that are useful for breeding. Increasing leaf vein density (concentration of vascular tissue per unit leaf area) has important implications for plant hydraulic properties and assimilate transport. It was an important step to improving photosynthetic rates in the evolution of both C3 and C4 species and is a foundation or prerequisite trait for C4 engineering in crops like rice (Oryza sativa). A previous high throughput screen identified five mutant rice lines (cv. IR64) with increased vein densities and associated narrower leaf widths (Feldman et al., 2014). Here, these high vein density rice variants were analyzed for properties related to photosynthesis. Two lines were identified as having significantly reduced mesophyll to bundle sheath cell number ratios. All five lines had 20% higher light saturated photosynthetic capacity per unit leaf area, higher maximum carboxylation rates, dark respiration rates and electron transport capacities. This was associated with no significant differences in leaf thickness, stomatal conductance or CO2 compensation point between mutants and the wild-type. The enhanced photosynthetic rate in these lines may be a result of increased RuBisCO and electron transport component amount and/or activity and/or enhanced transport of photoassimilates. We conclude that high vein density (associated with altered mesophyll cell length and number) is a trait that may confer increased photosynthetic efficiency without increased transpiration.

Rater Reliability of the Hardy Classification for Pituitary Adenomas in the Magnetic Resonance Imaging Era.

Objectives The Hardy classification is used to classify pituitary tumors for clinical and research purposes. The scale was developed using lateral skull radiographs and encephalograms, and its reliability has not been evaluated in the magnetic resonance imaging (MRI) era. Design Fifty preoperative MRI scans of biopsy-proven pituitary adenomas using the sellar invasion and suprasellar extension components of the Hardy scale were reviewed. Setting This study was a cohort study set at a single institution. Participants There were six independent raters. Main Outcome Measures The main outcome measures of this study were interrater reliability, intrarater reliability, and percent agreement. Results Overall interrater reliability of both Hardy subscales on MRI was strong. However, reliability of the intermediate scores was weak, and percent agreement among raters was poor (12-16%) using the full scales. Dichotomizing the scale into clinically useful groups maintained strong interrater reliability for the sellar invasion scale and increased the percent agreement for both scales. Conclusion This study raises important questions about the reliability of the original Hardy classification. Editing the measure to a clinically relevant dichotomous scale simplifies the rating process and may be useful for preoperative tumor characterization in the MRI era. Future research studies should use the dichotomized Hardy scale (sellar invasion Grades 0-III versus Grade IV, suprasellar extension Types 0-C versus Type D).