North American Database Research Articles

Comprehensive analysis of constitutional mismatch repair deficiency-associated non-Hodgkin lymphomas in a global cohort.

Constitutional mismatch repair deficiency syndrome (CMMRD) is a rare childhood cancer predisposition syndrome associated with a broad spectrum of malignancies, including non-Hodgkin lymphomas (NHL). Most patients die due to cancer before the age of 20years. Limited data exist on CMMRD-associated lymphomas and their outcome. We conducted a retrospective study including all CMMRD-associated NHL patients registered before 2020 in the European and North American databases or reported by members of the European Intergroup for Childhood Non-Hodgkin Lymphoma (EICNHL). Events considered to define event-free survival included relapse/progression, second malignancy (SML), or death, whichever occurred first. The analysis included 74 patients, with 20 having multiple metachronous NHL. The median age at diagnosis was 9.4years. Previous malignancies were reported in 36% of the patients, café au lait spots in 96%, and consanguinity in 54%. The initial lymphoma subtypes were 53 T-cell lymphoblastic lymphomas (T-LBL), four B-lymphoblastic lymphomas, and 17 mature B-cell non-Hodgkin lymphoma (B-NHL). All patients were treated with curative intent, with current chemotherapy regimens adapted to their subtype. The median follow-up was 8.7years. After the first lymphoma, the 5-year event-free and overall survival rates were, respectively, 23.5% [95% confidence interval (CI): 14.9-35.1] and 61.5% [95% CI: 49.6-72.1]. The 5-year cumulative risk of progression/relapse, SML or death as a first event was 20.8%, 52.9%, and 2.7%. Standard treatments for sporadic NHL are effective in most CMMRD-associated NHL cases, but multiple malignancies, including lymphomas, impair prognosis. Future strategies should evaluate the potential of less genotoxic therapies, including immunotherapy, in preventing SMLs while maintaining effective control of NHL.

Developing a Novel Prognostic Model Based on Muscle-Invasive Bladder Cancer Types: A Multicenter RetrospectiveCohort Study of Patients Who Received Radical Cystectomy and Chemotherapy.

To develop a prognostic model to manage patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC) and chemotherapy. Clinicopathologic characteristics and survival data were collated from a North American database to develop a model. Genomic and clinicopathologic data were also obtained from European and Asian databases to externally validate the model. Patients were classified as either "primary" or "progressive" MIBC according to non-muscle invasive stage history. Optimized cancer-specific survival (CSS) models, based on MIBC types, were constructed using Cox's proportional hazard regression. Differences of biological function and tumor immunity, between two risk-based groups stratified according to the prognostic model, were estimated. There were 2631 participants in the American cohort, 291 in the European cohort and 142 in the Asian cohort. Under Cox's regression analysis, tumor stage, lymph node stage, age, ethnicity, and MIBC types were independent CSS predictors (all p < 0.05). The constructed nomogram, whichintegratedthese variables, improved the predictivepower. This model had good discrimination and calibration. Patients were categorized into high- or low-risk groups according to the total points calculated. Kaplan-Meier curves revealed that patients in the high-risk group had poorer survival (p < 0.001). This was confirmed with two external validation cohorts (both with p < 0.001). Higher stromal scores and increased M0 and M2 macrophage numbers were observed in samples from the high-risk group, whereas regulatory T cells had lower infiltration in these populations (all with p < 0.05). This MIBC type-based nomogram provides accurate CSS predictions, which could help improve patient management and clinical decision-making.

Biogeography and Species Durations of Selected Cenozoic Shallow and Deep-Water Smaller Calcareous Benthic Foraminifera – A Review

Abstract Most previous accounts summarising the biogeography and species durations of smaller calcareous benthic foraminifera have been based on literature reviews or on a massive North American database that had been taxonomically standardised. In this review we limit consideration to extant and fossil families or genera (from nearshore, open shelf, and deep-sea environments) with modern reviews that have standardised their global morphotaxonomy and where available, are complimented by molecular studies. We confirm previous studies that indicate most shelf species have limited geographic ranges and the majority of deep-water species are widespread and cosmopolitan or nearly so. In our intertidal and inner shelf groups only one species (molecular and morphological), Ammonia veneta, has a cosmopolitan distribution, although four warm-water morphospecies, of Ammonia and Rugobolivinella, have or had distributions that spanned more than one ocean in equatorial latitudes. The majority of both warm- and cool-water species in these groups are regionally or locally-restricted endemics (92% of Bolivinellidae, 100% of Tubulogenerina, 73% of Ammoniidae). The biogeographic distribution of the two rarer, warm-water groups (Bolivinellidae, Tubulogenerina) changed dramatically through the Cenozoic with the Paleocene–Eocene North American–European distribution of Bolivinellidae switching to purely Indo-Pacific by the Pliocene–Quaternary. In our shelf–upper bathyal groups (Notorotaliiidae, Plectofrondiculariidae), two genera have been restricted to the Southern Hemisphere since their Eocene originations with their greatest diversity throughout in New Zealand and Australia, respectively. The dominantly cold-water notorotaliid genus Buccella has a biogeographic distribution largely restricted to the Arctic Ocean and both coasts of North and South America. Most notorotaliid species are locally or regionally endemic (100% of Notorotalia, Parrellina, Porosorotalia, 75% of Buccella). At least 50–60% of species in five extinct mid-bathyal–abyssal families are cosmopolitan and have been throughout the Cenozoic since their originations. The majority of these deep-sea species with more-restricted distributions are rare, and many could possibly be more widespread with further extensive study. This review found that the shortest mean species durations (4–5 myrs) occur in two groups of rather rare, tropical–subtropical inner-shelf foraminifera with many locally endemic species. In cooler and progressively deeper water environments the mean species durations increase to 7–11 myrs for temperate shelf–bathyal taxa (Notorotaliidae), 20 myrs for an extinct mid-shelf to bathyal family (Plectofrondiculariidae) and 41–50 myrs for five extinct mid-bathyal–abyssal families (Chrysalogoniidae, Ellipsoidinidae, Glandulonodosariidae, Pleurostomellidae, Stilostomellidae). One species in each of four of these deep-water families had a species duration of 150–120 myrs.

TOP-045 - The effect of precipitating factors for hepatorenal syndrome on response to terlipressin treatment: a subgroup analysis of a pooled North American database

TOP-045 - The effect of precipitating factors for hepatorenal syndrome on response to terlipressin treatment: a subgroup analysis of a pooled North American database

Robotic Versus Open Hepatectomy in North America: Does the Robotic Approach Improve Outcomes?

Introduction: Minimally Invasive Hepatectomy has been shown to be associated with improved outcomes, but data are limited to small studies. The aim of this analysis was to compare robotic and open hepatectomy in a large North American database.

Future Perspectives on the TNM Staging for Lung Cancer.

Simple SummaryThe tumor, lymph node, and metastases classification of lung cancer describes how big the tumor is and what structures it invades; whether the lymph nodes are involved or not, and, if they are involved, where they are in the chest; and whether there are tumor implants in other organs distant from the lung. This classification of lung cancer was proposed in 1966 and it has undergone periodic revisions. The revisions for its 7th and 8th editions were based on a large amount of international data from patients treated with different therapeutic modalities. New data are being registered now to inform the forthcoming 9th edition. A potential innovation of this edition will be the combination of this classification with other prognostic factors, such as mutations of the genetic code of the cancer cells among others, to achieve a more personalized prognosis for individual patients.Since its conception by Pierre Denoix in the mid-20th century, the tumor, node, and metastasis (TNM) classification has undergone seven revisions. The North American database managed by Clifton Mountain was used to inform the 2nd to the 6th editions, and an international database collected by the International Association for the Study of Lung Cancer, promoted by Peter Goldstraw, was used to inform the 7th and the 8th editions. In these two latest editions, it was evident that the impact of tumor size was much greater than it was suggested in previous editions; that the amount of nodal disease had prognostic relevance; and that the number and location of the distant metastases had prognostic implications. However, the TNM classification is not the only prognostic factor. Data are being collected now to inform the 9th edition of the TNM classification, scheduled for publication in 2024. Patient-, environment-, and tumor-related factors, including biomarkers (genetic biomarkers, copy number alterations, and protein alterations) are being collected to combine them in prognostic groups to enhance the prognosis provided by the mere anatomic extent of the tumor, and to offer a more personalized prognosis to an individual patient. International collaboration is essential to build a large and detailed database to achieve these objectives.

Knowledge Organization For Open Scholarship

This introductory piece explores the role that subject description—the work of determining an object’s aboutness and assigning relevant terms—has in creating infrastructures for open scholarship. Of particular concern is the potential to adopt the dominant, universalist systems common across North American libraries and databases, or to shift to situated and accountable systems that take care to describe objects consistent with the values of local communities of creators and readers.

Impact of improved low-density lipoprotein cholesterol assessment on guideline classification in the modern treatment era—Results from a racially diverse Brazilian cross-sectional study

The Martin/Hopkins low-density lipoprotein cholesterol equation (LDL-CN) was previously demonstrated as more accurate than Friedewald LDL-C estimation (LDL-CF) in a North American database not able to take race into account. We hypothesized that LDL-CN would be more accurate than LDL-CF and correlate better with LDL particle number (LDL-P) in a racially diverse Brazilian cohort. We performed a cross-sectional analysis of 4897 participants in the Brazilian Longitudinal Study of Adult Health, assessing LDL-CF and LDL-CN accuracy via overlap with ultracentrifugation-based measurement among clinical guideline LDL-C categories as well as mg/dL and percent error differences. We analyzed by triglyceride categories and correlated LDL-C estimation with LDL-P. LDL-CN demonstrated improved accuracy at 70 to <100 and <70mg/dL (P<.001), with large errors ≥20mg/dL about 9 times more frequent in LDL-CF at LDL-C <70mg/dL, mainly due to underestimation. Among individuals with LDL-C <70mg/dL and triglycerides ≥150mg/dL, 65% vs 100% of ultracentrifugation-based low-density lipoprotein cholesterol calculation fell within appropriate categories of estimated LDL-CF and LDL-CN, respectively (P<.001). Similar results were observed when analyzed for age, sex, and race. Participants at LDL-C <70 and 70 to <100mg/dL with discordantly elevated LDL-CN vs LDL-CF had a 58.5% and 41.5% higher LDL-P than those with concordance (P<.0001), respectively. In a diverse Brazilian cohort, LDL-CN was more accurate than LDL-CF at low LDL-C and high triglycerides. LDL-CN may avoid underestimation of LDL-C and better reflect atherogenic lipid burden in low particle size, high particle count states.

Towards the 9th Edition of the Tumour, Node and Metastasis Classification of Lung Cancer. A Historical Appraisal and Future Perspectives.

Since 1966 the classification of anatomic extent of lung cancer, based on the primary tumour (T), the loco-regional lymph nodes (N) and the metastases (M) has been used in the management of lung cancer patients. Developed by Pierre Denoix, it was adopted by the Union for International Cancer Control and the American Joint Committee on Cancer. Clifton Mountain revised the second through the sixth editions based on a North American database of more than 5000 patients. For the seventh and the eighth editions, the International Association for the Study of Lung Cancer (IASLC) collected international databases of around 100,000 patients worldwide that allowed the introduction of innovations in both editions, namely the subdivision of the T and M categories based on tumour size and on the location and number of metastases, respectively. The revisions also showed the prognostic relevance of the quantification of nodal disease, and proposed recommendations on how to measure tumour size for solid lung cancers, part-solid adenocarcinomas, and for lung cancers removed after induction therapy. Despite the innovations, prognosis based on the anatomic extent is limited, because prognosis depends on factors related to the tumour, the patient and the environment. For the 9th edition, these factors, especially genetic biomarkers, will be combined in prognostic groups to refine prognosis at clinical and pathologic staging. To achieve this challenging objective, international cooperation is essential, and the IASLC Staging and Prognostic Factors Committee counts on it for the development of the 9th edition due to be published in 2024.

Towards the 9th Edition of the Tumour, Node and Metastasis Classification of Lung Cancer. A Historical Appraisal and Future Perspectives

Since 1966 the classification of anatomic extent of lung cancer, based on the primary tumour (T), the loco-regional lymph nodes (N) and the metastases (M) has been used in the management of lung cancer patients. Developed by Pierre Denoix, it was adopted by the Union for International Cancer Control and the American Joint Committee on Cancer. Clifton Mountain revised the second through the sixth editions based on a North American database of more than 5000 patients. For the seventh and the eighth editions, the International Association for the Study of Lung Cancer (IASLC) collected international databases of around 100,000 patients worldwide that allowed the introduction of innovations in both editions, namely the subdivision of the T and M categories based on tumour size and on the location and number of metastases, respectively. The revisions also showed the prognostic relevance of the quantification of nodal disease, and proposed recommendations on how to measure tumour size for solid lung cancers, part-solid adenocarcinomas, and for lung cancers removed after induction therapy. Despite the innovations, prognosis based on the anatomic extent is limited, because prognosis depends on factors related to the tumour, the patient and the environment. For the 9th edition, these factors, especially genetic biomarkers, will be combined in prognostic groups to refine prognosis at clinical and pathologic staging. To achieve this challenging objective, international cooperation is essential, and the IASLC Staging and Prognostic Factors Committee counts on it for the development of the 9th edition due to be published in 2024.

New Directions in the Computational Analysis of Biblical Hebrew Grammar

The concern of the paper is to highlight how computational analysis of Biblical Hebrew grammar can now be done in very sophisticated ways and with insightful results for exegesis. Three databases, namely, the Eep Talstra Centre for Bible and Computer (ETCBC) Database, the Accordance Hebrew Syntactic Database, and the Andersen-Forbes Syntactic Database,are compared in terms of their relation to linguistic theory (or, theories), the nature and spectrum of retrieved data, and the representation of synchronic and diachronic linguistic variation. Interaction between different contexts, including the African context, are promoted namely between linguists working on Biblical Hebrew and exegetes working on the Hebrew Bible by illustrating how exegesis and language are intimately connected, as well as among geographical contexts by comparing a European database (ETCBC), a North American database (Accordance) and a Southern hemisphere database (Andersen-Forbes).

First Population-Based Report of Infants with Congenital Diaphragmatic Hernia: 30-Day Outcomes from the American College of Surgeons National Quality Improvement Program.

The American College of Surgeons has developed a registry, the National Quality Improvement Program Pediatric (NSQIP-P), that provides participating centers with high-quality surgical outcome data for children. Herein, we aimed to analyze for the first time the short-term outcomes of live-born infants with congenital diaphragmatic hernia (CDH) registered on this large North American database. During 2015 to 2016, up to 101 participating centers uploaded 95 perioperative data points on the NSQIP-P database for patients that underwent surgical repair of CDH. The demographics, peri-, and post-operative data (up to 30 days following surgical repair) of infants with CDH were reviewed. Binary logistic regression was performed to test associations between risk factors and mortality. There were 432 (61% male) infants, who underwent CDH surgical repair during the study period. The prematurity rate (gestational age < 37 weeks) was 17%. The majority of infants (82%) had cardiac risk factors identified (72% were reported as major/severe). Extracorporeal membrane oxygenation (ECMO) was employed in 13% of patients prior to surgery. The majority of infants (83%) were ventilated preoperatively, and 34% received inotropes. Median age at surgery was 5 (0-74) days. CDH repair was attempted via thoracoscopy in 18% (n = 79) infants, but with a high rate of conversion to open surgery (n = 32, 41%). The postoperative 30-day mortality rate was 9%. At binary logistic regression, major cardiac risk factors (odds ratio [OR], 1.7 [0.9-3.2], p = 0.095), Appearance, Pulse, Grimace, Activity, and Respiration at 1 minute (OR, 0.7 per unit [0.5-0.8], p < 0.005), and birth weight (OR, 0.5 per kg [0.2-1.0], p < 0.05) were retained in the final model as significantly associated with mortality. This is the first report on CDH outcomes from the NSQIP-P database. Utilization of ECMO was low compared with single-center studies from North America. The early postoperative mortality rate of babies with CDH considered suitable for surgery remains high.

Increasing rate of lymph node invasion in patients with prostate cancer treated with radical prostatectomy and lymph node dissection

ObjectivesTo investigate lymph node invasion (LNI) rates in prostate cancer (PCa) patients. Recent studies demonstrated an inverse stage migration in PCa patients toward more advanced and unfavorable diseases. We hypothesized that this trend is also evident in LNI rates, in PCa patients treated with radical prostatectomy (RP) and pelvic lymph node dissection (PLND). Patients and methodsWithin the Surveillance, Epidemiology, and End Results database (2004–2014), we identified patients who underwent RP and PLND. Annual trends of LNI rates and PLND extent were plotted. Univariable and multivariable logistic regression models tested the hypothesis that LNI rates are increasing annually, even after adjustment for clinical or pathological characteristics. ResultsOf 96,874 patients treated with RP and PLND, 4.1% (n = 4,002) exhibited LNI. The rate of LNI (2.5%–6.6%.), the mean (6.5–8.4) and median (5–6) number of removed lymph nodes increased during the study period. In multivariable logistic regression models, more contemporary year of diagnosis was associated with higher LNI rate, when year of diagnosis was modeled as a continuous, categorized or cubic spline variable, with adjustment for either clinical (prostate specific antigen, clinical tumor stage, and biopsy Gleason group) or pathological characteristics (pathologic tumor stage and Gleason group), as well as PLND extent (number of removed lymph nodes). ConclusionWe confirmed the hypothesis about increasing LNI rate over time in RP patients. This observation implies an increasing rate of unfavorable PCa defined as LNI. This finding is novel for contemporary epidemiological North American or European databases.

Synthetic Cannabinoid Exposure in Adolescents Presenting for Emergency Care.

The objective of this study was to characterize the clinical picture and management of synthetic cannabinoid exposure in a cohort of adolescents. Using the 45 participating sites of the Toxicology Investigators Consortium Registry, a North American database, we conducted an observational study of a prospectively collected cohort. We identified all adolescent (12-19 years) cases of synthetic cannabinoid exposure who have received medical toxicology consultation between January 2012 and December 2016. Clinical and demographic data were collected including age, sex, circumstances surrounding exposure, coingestants, clinical manifestations, treatment, disposition, and outcome. We identified 75 adolescents who presented to the emergency department with synthetic cannabinoid exposure. Most were male (91%) and between the ages of 16 and 19 (66%). The most common symptoms were neuropsychiatric with 50 adolescents (67%) exhibiting central nervous system (CNS) manifestations. There was no predominant toxidrome, and 9 patients (12%) were mechanically ventilated. Mainstay of treatment was supportive care. No deaths were reported. Synthetic cannabinoid exposure in adolescents is primarily characterized by CNS manifestations, which are varied and may be life-threatening. Frontline caregivers should maintain a high index of suspicion for synthetic cannabinoids, especially in adolescents who present with unexplained CNS manifestations, as there is no specific toxidrome or confirmatory rapid drug screen to detect them.

Mesenchymal Stromal Cell Therapy: After the Gold Rush.

Few medical advancements have captivated public interest as much as stem cell therapies. In fact, one of the original stem cell therapies was described in this very journal nearly 50 years ago1,2: the mesenchymal stem cell. Now known as mesenchymal stromal cells (MSCs),3 a more appropriate name due to their limited capacity to differentiate into somatic cell types, clinical evidence for their potential benefits is steadily mounting. The current nomenclature change reflects 2 important clinical advantages for MSC therapy in comparison to bona fide stem cells: no risk of teratoma formation and fewer ethical concerns related to isolation and expansion methods. Moreover, the ease in isolation and expansion makes MSC therapy economically attractive. These advantages coupled with credible immunosuppressive effects experimentally have led to much interest in their use in solid organ,4 cellular,5 and vascularized composite transplantation6,7 as well as other immune-mediated pathologies,8 and a rush toward clinical trials. Although there is some evidence that these cells have therapeutic effects through their regenerative properties,9-11 it is principally their broad immunosuppressive activity, and perhaps induction of regulatory T cells,12 that is of interest. The first clinical studies of MSC therapy were reported over a decade ago and hundreds of trials continue to be registered in European and North American databases. However, very little is understood regarding the clinical efficacy of these cells in transplantation. The paucity of evidence is striking given the widespread commercialization and availability of MSC therapy in many countries. The summary of the current state of the art of MSC therapy in renal transplantation from Reinders and colleagues13 is therefore timely and welcome. When investigating the field, the lack of consistency in cell description and the variety of isolation techniques mean that comparisons between studies are impossible. However, the International Society for Cellular Therapy’s position statement14 has provided much needed clarity. Their definition requires 3 components for defining MSCs: adherence to plastic, specific surface antigen expression, and the ability to differentiate into osteoblasts, adipocytes, and chondrocytes in vitro. Naturally, these are minimum requirements, and additional clinical release criteria will be required in different countries. Helpfully, the description provided in the review in this issue of Transplantation provides useful information regarding the types of MSCs used in ongoing trials in renal transplantation. MSCs may be derived from several sources, with each source exhibiting specific immunological properties.15 The most commonly used sources in reported clinical trials are bone marrow and adipose tissue. Reinders and colleagues16 summarized 7 published trials in renal transplantation with a total of 141 patients treated with MSCs derived from bone marrow. In these limited studies, there are hints of improved outcomes with reduced requirements for drug immunosuppression as well as enhanced renal function. However, the difficulty in defining useful short-term endpoints in renal transplantation clinical trials limits the ability to understand the true efficacy of MSC therapy. More concerning is the evidence of an increase in the incidence of opportunistic infections which was reported in a study from the same group in Leiden. This is not unexpected given that MSCs exert immunosuppressive effects that are nonspecific and not regulated or directed in the same manner as a leukocyte. Ostensibly, this broad activity raises some doubts regarding the overall benefits of MSC therapy versus traditional immunosuppression.17 There remain many questions regarding the specific techniques of clinical application as well as the practicalities of Good Manufacturing Practice manufacture, an issue which is examined by Reinders et al. A discussion of these issues is crucial given the lack of consistency and anecdotal nature of many clinical trials.

Second annual Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) report: Pre-implant characteristics and outcomes

Expanded use of pediatric ventricular assist devices (VADs) has decreased mortality in children awaiting heart transplantation. Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs), a National Heart, Lung, and Blood Institute-sponsored North American database, provides a platform to understand this emerging population. Between September 2012 and September 2016, patients aged younger than 19 years who underwent VAD implantation were enrolled in Pedimacs. FDA approved durable devices as well as temporary support devices were included. The second annual report updates the current Pedimacs data. Patients implanted with temporary devices are included in Pedimacs and this analysis includes this group of paracorporeal continuous flow VADs. Over the 4 years, 42 hospitals implanted 432 devices in 364 patients less than 19 yrs of age. Diagnoses included cardiomyopathy in 223 (61%), myocarditis in 41 (11%), and congenital heart disease in 77 (21%), of which 48 had single-ventricle physiology. At implant, 87% were at Intermacs patient profile 1 or 2. The age distribution of children (59% male) supported on VAD included 69 (19%) aged younger than 1 year, 66 (18%) aged 1 to 6 years, 56 (15%) aged 6 to 10 years, and 173 (48%) aged 11 to 19 years. Median follow-up was 2.2 months (range, 1 day to 41.5 months). Median (interquartile) age at implant was 1.7 (0.3-10.0) years for paracorporeal continuous-flow pumps (n = 60), 1.7 (0.4-5.3) years for paracorporeal pulsatile pumps (n = 105), and 15.0 (11.3-16.9) years for implantable continuous-flow pumps (n = 174). Support strategies included LVAD in 293 (80%), biventricular device in 55 (15%), and total artificial heart in 8 (2%). Nearly 50% of patients underwent transplantation within 6 months, with overall mortality of 19%. Adverse event burden continues to be high. Pedimacs constitutes the largest longitudinal pediatric VAD registry. Preimplant data across centers will be helpful at creating shared protocols with which to improve outcomes. Adverse events continue to be the major challenge, especially among the young critically ill children with complex congenital disease.

Relations between Some Horizontal‐Component Ground‐Motion Intensity Measures Used in Practice

Various measures using the two horizontal components of recorded ground motions have been used in a number of studies that derive ground‐motion prediction equations and construct maps of shaking intensity. We update relations between a number of these measures, including those in Boore et al. (2006) and Boore (2010), using the large and carefully constructed global database of ground motions from crustal earthquakes in active tectonic regions developed as part of the Pacific Earthquake Engineering Research Center–Next Generation Attenuation‐West2 project. The ratios from the expanded datasets generally agree to within a few percent of the previously published ratios. We also provide some ratios that were not considered before, some of which will be useful in applications such as constructing ShakeMaps. Finally, we compare two important ratios with those from a large central and eastern North American database and from many records from subduction earthquakes in Japan and Taiwan. In general, the ratios from these regions are within several percent of those from crustal earthquakes in active tectonic regions. [Electronic Supplement:][1] Figures of ground‐motion intensity measure (GMIM) ratios, and csv files with average ratios and the coefficients of fits to the ratios. [1]: http://www.bssaonline.org/lookup/suppl/doi:10.1785/0120160250/-/DC1

Selecting caudal fusion levels: 2year functional and stiffness outcomes with matched pairs analysis in multilevel fusion to L5 versus S1.

Controversy persists as to whether to end multilevel thoracolumbar fusions caudally at L5 or S1. Some argue that stopping at L5 may preserve greater function, but there are few data comparing functional limitations due to lumbar stiffness in patients with fusion to L5 versus S1. The aim of this study was to evaluate whether patients undergoing multilevel thoracolumbar fusions with an L5 caudal endpoint have a better lumbosacral function than patients with an S1 caudal endpoint. Patients undergoing successful thoracolumbar fusion of 5 or more levels to L5 or S1, with solid fusion at 2year follow-up, were examined from a single European center in addition to a multi-center North American database of 237 patients. In total, 40 patients with a distal stopping point of L5 were matched with a subset of 40 patients with a distal endpoint of S1±pelvic fixation. The L5 and S1 groups were matched for the final Oswestry Disability Index (ODI), Sagittal Vertical Axis (SVA C7-S1), number of fusion levels, and age. Impacts of lumbar stiffness on function as measured by the Lumbar Stiffness Disability Index (LSDI) were compared using the conditional logistic regression. After matching, there was no significant difference between the S1 and L5 groups for the final ODI (29.22±21.6 for S1 versus 29.21±21.7 for L5; p=0.98), SVA (29.5±40.3mm for S1 versus 33.7±37.1mm for L5; p=0.97), mean age (61.6±11.0years for S1 versus 58.3±12.6years for L5; p=0.23), and number of fusion levels (9.7±3.3 levels for S1 versus 9.0±3 levels for L5; p=0.34). The final 2-year postoperative LSDI scores were not significantly different between the S1 group (28.08±21.47) and L5 group(29.21±21.66) (hazard ratio 0.99, 95% CI 0.97-1.03, p=0.81). The analysis of patients with multilevel thoracolumbar fusions demonstrated that after minimum 2year follow-up, self-reported functional impacts of lumbar stiffness were not significantly different between the patients with distal endpoints of L5 versus S1. The choice of distal fusion level of L5 does not appear to retain sufficient spinal flexibility to substantially affect postoperative function. Level III.

An unexpectedly high rate of revisions and removals in deep brain stimulation surgery: Analysis of multiple databases

IntroductionDeep brain stimulation (DBS) is an established therapy for movement disorders, and is under active investigation for other neurologic and psychiatric indications. While many studies describe outcomes and complications related to stimulation therapies, the majority of these are from large academic centers, and results may differ from those in general neurosurgical practice. MethodsUsing data from both the Centers for Medicare and Medicaid Services (CMS) and the National Surgical Quality Improvement Program (NSQIP), we identified all DBS procedures related to primary placement, revision, or removal of intracranial electrodes. Cases of cortical stimulation and stimulation for epilepsy were excluded. ResultsOver 28,000 cases of DBS electrode placement, revision, and removal were identified during the years 2004–2013. In the Medicare dataset, 15.2% and of these procedures were for intracranial electrode revision or removal, compared to 34.0% in the NSQIP dataset. In NSQIP, significant predictors of revision and removal were decreased age (odds ratio (OR) of 0.96; 95% CI: 0.94, 0.98) and higher ASA classification (OR 2.41; 95% CI: 1.22, 4.75). Up to 48.5% of revisions may have been due to improper targeting or lack of therapeutic effect. ConclusionData from multiple North American databases suggest that intracranial neurostimulation therapies have a rate of revision and removal higher than previously reported, between 15.2 and 34.0%. While there are many limitations to registry-based studies, there is a clear need to better track and understand the true prevalence and nature of such failures as they occur in the wider surgical community.

Practical implications for genetic modeling in the genomics era

Genetic models convert data into estimated breeding values and other information useful to breeders. The goal is to provide accurate and timely predictions of the future performance for each animal (or embryo). Modeling involves defining traits, editing raw data, removing environmental effects, including genetic by environmental interactions and correlations among traits, and accounting for nonadditive inheritance or nonnormal distributions. Data include phenotypes and pedigrees during the last century and genotypes within the last decade. The genomic data can include single nucleotide polymorphisms, quantitative trait loci, insertions, deletions, and haplotypes. Subsets must be selected to reduce computation because total numbers of variants that can be imputed have increased rapidly from thousands to millions. Current computation using 60,671 markers takes just a few days. Nonlinear models can account for the nonnormal distribution of genomic effects, but reliability is usually better than that of linear models only for traits influenced by major genes. Numbers of genotyped animals have also increased rapidly in the joint North American database from a few thousand in 2009 to over 1 million in 2015. Most are young females and will contribute to estimating allele effects in the future, but only about 150,000 have phenotypes so far. Genomic preselection can bias traditional animal models because Mendelian sampling of phenotyped progeny and mates is no longer expected to average zero; however, estimates of bias are small in current US data. Single-step models that combine pedigree and genomic relationships can account for preselection, but approximations are required for affordable computation. Traditional animal models may include all breeds and crossbreds, but most genomic evaluations are still computed within breed. Models that include inbreeding, heterosis, dominance, and interactions can improve predictions for individual matings. Multitrait genomic models may be preferred for traits with many missing records or when foreign records are included as pseudo-observations, but most countries use multitrait traditional evaluations followed by single-trait genomic evaluations. Genomic reliabilities are about 70% for the more heritable traits. Researchers must choose from many available models and explain how the models work so that breeders can more confidently apply the predictions in their selection programs.