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We present the new features available in the recent release of SuperLU_DIST , Version 8.1.1. SuperLU_DIST is a distributed-memory parallel sparse direct solver. The new features include (1) a 3D communication-avoiding algorithm framework that trades off inter-process communication for selective memory duplication, (2) multi-GPU support for both NVIDIA GPUs and AMD GPUs, and (3) mixed-precision routines that perform single-precision LU factorization and double-precision iterative refinement. Apart from the algorithm improvements, we also modernized the software build system to use CMake and Spack package installation tools to simplify the installation procedure. Throughout the article, we describe in detail the pertinent performance-sensitive parameters associated with each new algorithmic feature, show how they are exposed to the users, and give general guidance of how to set these parameters. We illustrate that the solver’s performance both in time and memory can be greatly improved after systematic tuning of the parameters, depending on the input sparse matrix and underlying hardware.

Trogocytosis is an active process that transfers surface material from targeted to effector cells. Using multiple in vivo tumor models and clinical data, we report that chimeric antigen receptor (CAR) activation in natural killer (NK) cells promoted transfer of the CAR cognate antigen from tumor to NK cells, resulting in (1) lower tumor antigen density, thus impairing the ability of CAR-NK cells to engage with their target, and (2) induced self-recognition and continuous CAR-mediated engagement, resulting in fratricide of trogocytic antigen-expressing NK cells (NKsupTROG+/sup) and NK cell hyporesponsiveness. This phenomenon could be offset by a dual-CAR system incorporating both an activating CAR against the cognate tumor antigen and an NK self-recognizing inhibitory CAR that transferred a 'don't kill me' signal to NK cells upon engagement with their TROGsup+/supsiblings. This system prevented trogocytic antigen-mediated fratricide, while sparing activating CAR signaling against the tumor antigen, and resulted in enhanced CAR-NK cell activity.

PURPOSE: Cerebral palsy (CP) and spina bifida (SB) are pediatric-onset disabilities. Adults living with CP/SB are in a greater need of preventive care than the general population due to their increased risk for chronic diseases. Our objective was to compare White/Black and White/Hispanic inequities in the use of preventive services. METHODS: Using 2007-2017 private claims data, we identified a total of 11,635 adults with CP/BS. Of these, 8,935 were White, 1,457 Black, and 1,243 Hispanic. We matched health-related variables (age, sex, comorbid conditions) between White adults and those in each minority subpopulation. Generalized estimating equations were used and all models were adjusted for age, sex, comorbidities, income, education, and US Census divisions. Outcomes of interest were: (1) any office visit; (2) any physical/occupational therapy; (3) wellness visit; (4) bone density screening; (5) cholesterol screening; and (6) diabetes screening. RESULTS: The rate of recommended services for all subpopulations of adults with CP/SB was low. Compared with White adults, Hispanic adults had lower odds of wellness visits (odds ratio [OR] = 0.71, 95% CI, 0.53-0.96) but higher odds of diabetes screening (OR = 1.48, 95% CI, 1.13-1.93). Compared with White adults, Black adults had lower odds of wellness visits (OR = 0.50, 95% CI, 0.24-1.00) and bone density screening (OR = 0.54, 95% CI, 0.31-0.95). CONCLUSIONS: Preventive service use among adults with CP/SB was low. Large White-minority disparities in wellness visits were observed. Interventions to address physical accessibility, adoption of telehealth, and increased clinician education may mitigate these disparities, particularly if initiatives target minority populations.

Surgery residency program websites (SRW) are an important source of information for prospective applicants. The COVID-19 pandemic spurred a pivot from the traditional in-person interview format to interviews via virtual platforms. Because of the inability to meet in person, the information provided on program websites takes on an increased relevance to applicants. We hypothesized that SRW may be missing content important to applicants. Our study aims to assess SRW for the content which impacts the applicant decision-making process.An internal survey distributed to fourth-year medical students in 2020 at a single academic institution identified the website content most important to applicants. A list of ACGME-accredited SRW as of December 1, 2020 was obtained. Using the Fellowship and Residency Electronic and Interactive Database, websites were assessed for content parameters identified by the survey.Medical students applying to surgical specialties identified fellowship acquisition (94%), faculty information (88%), application contact information (82%), and resident wellness (77%) as the most important website content. Review of SRW websites identified content pertaining to fellowship acquisition and resident wellness in only 60% and 27% of cases respectively. Overall, the SRW of university programs included the most content parameters, followed by hybrid programs, then community programs.Many SRW are missing information that applicants deem important in their decision-making process. Most notably, there is a relative deficiency in information pertaining to fellowship match results and resident wellness. University based programs tend to include more of this information on their websites. SRW should continue to adapt to meet the needs of applicants in an increasingly virtual age.

To examine the risk of potentially preventable hospitalizations (PPHs) for adults (18 years or older) with traumatic spinal cord injury (TSCI) to identify the most common types of preventable hospitalizations and their associative risk factors.Cohort study.Using 2007-2017 U.S. claims data from the Optum Clinformatics Data Mart, we identified adults (18 years or older) with diagnosis of TSCI (n=5380). Adults without TSCI diagnosis were included as controls (n=1,074,729). Using age and sex, we matched individuals with and without TSCI (n=5173) with propensity scores to address potential selection bias. Generalized linear regression was applied to examine the risk of TSCI on PPHs. Models were adjusted for age; sex; race and ethnicity; Elixhauser comorbidity count; any cardiometabolic, psychological, and musculoskeletal chronic conditions; U.S. Census Division; socioeconomic variables; and use of certain preventative care services. Adjusted odds ratios were compared within a 4-year follow-up period.Adults with and without TSCI (N=5,173).Not applicable.Any PPH and specific PPHs RESULTS: Adults with TSCI had higher risk for any PPH (odds ratio [OR], 1.67; 95% CI,1.20-2.32), as well as PPHs because of urinary tract infection (UTI) (OR, 3.78; 95% CI, 2.47-5.79), hypertension (OR, 3.77; 95% CI, 1.54-9.21), diabetes long-term complications (OR, 2.54; 95% CI, 1.34-4.80), and pneumonia (OR, 1.71; 95% CI. 1.21-2.41). Annual wellness visit was associated with reduced PPH risk compared with cases and controls without annual wellness visit (OR, 0.57; 95% CI, 0.46-0.71) and among people with TSCI (OR, 0.69; 95% CI, 0.55-0.86) compared with cases without annual wellness visit.Adults with TSCI are at a heightened risk for PPH. They are also more susceptible to certain PPHs such as UTIs, pneumonia, and heart failure. Encouraging the use of preventative or health-promoting services, especially for respiratory and urinary outcomes, may reduce PPHs among adults with TSCI.

To compare the prevalence and incidence of, and adjusted hazards for comorbidities among adults with traumatic spinal cord injuries (TSCIs) across insurance types (private vs governmental insurance) in the United States.Privately insured (N=9081) and Medicare (N=7645) beneficiaries with a diagnosis of TSCI were included. Prevalence and incidence estimates of common psychological, cardiometabolic, and musculoskeletal morbidities were compared at baseline and at 4-years after index diagnosis, respectively. Survival models were used to quantify hazard ratios (HRs) for outcomes, controlling for insurance type, sociodemographic characteristics, and other comorbidities. Sensitivity analyses were conducted to determine the effects of insurance and race/ethnicity.Adults with TSCIs on Medicare had a higher prevalence of any psychological (54.7% vs 35.4%), cardiometabolic (74.7% vs 70.1%), and musculoskeletal (72.8% vs 66.3%) morbidity than privately insured adults with TSCIs. Similarly, the 4-year incidences of most psychological (eg, depression: 37.6% [Medicare] vs 24.2% [private]), cardiometabolic (eg, type 2 diabetes: 22.5% [Medicare] vs 12.9% [private], and musculoskeletal (eg, osteoarthritis: 42.1% [Medicare] vs 34.6% [private]) morbidities were considerably higher among adults with TSCIs on Medicare. Adjusted survival models found that adults with TSCIs on Medicare had a greater hazard for developing psychological (HR, 1.40; 95% CI, 1.31-1.50) and cardiometabolic (HR, 1.21; 95% CI, 1.10-1.33) morbidities compared with privately insured adults with TSCI. There was evidence of both insurance and racial disparities.Adults with TSCIs on Medicare had significantly higher prevalence and risk for developing common physical and mental health comorbidities, compared with privately insured adults with TSCIs.

Most patients with multiple myeloma (MM) undergoing autologous hematopoietic stem cell transplantation (autoHCT) eventually relapse, perhaps due to the presence of clonal plasma cells (CPC) in the autograft. We conducted a retrospective analysis to evaluate the impact of CPC in the autograft on the outcomes of high-risk chromosomal abnormalities (HRMM) patients undergoing autoHCT between 2008 and 2018. Patients were divided into CPC+ or CPC− in the autograft by next-generation flow cytometry (NGF). There were 75 CPC + autografts (18%) and 341 CPC− (82%). The CPC + group was less likely to achieve MRD-negative complete remission post-transplant (11% vs. 42%; p p p = 0.006) and OS (HR 7.04, p = 0.002) compared to CPC-. In multivariable analysis, the degree of CPC positivity in the autograft was independently predictive of worse PFS (HR 1.50, p = 0.001) and OS (HR 1.37, p = 0.001). In conclusion, both the presence and degree of CPC in the autograft were highly predictive of inferior PFS and OS.

Upregulated or downregulated genes by PJA1 knockdown and TGF-β1 streatment in HepG2 cells

Characteristics of HCC patients with PJA1 genetic alterations

Supplementary Materials and Methods

Upregulated or downregulated genes in samples expressing a high level of PJA1

RING-finger E3 ligases are instrumental in the regulation of inflammatory cascades, apoptosis, and cancer. However, their roles are relatively unknown in TGFβ/SMAD signaling. SMAD3 and its adaptors, such as β2SP, are important mediators of TGFβ signaling and regulate gene expression to suppress stem cell–like phenotypes in diverse cancers, including hepatocellular carcinoma (HCC). Here, PJA1, an E3 ligase, promoted ubiquitination and degradation of phosphorylated SMAD3 and impaired a SMAD3/β2SP-dependent tumor-suppressing pathway in multiple HCC cell lines. In mice deficient for SMAD3 (Smad3+/−), PJA1 overexpression promoted the transformation of liver stem cells. Analysis of genes regulated by PJA1 knockdown and TGFβ1 signaling revealed 1,584 co-upregulated genes and 1,280 co-downregulated genes, including many implicated in cancer. The E3 ligase inhibitor RTA405 enhanced SMAD3-regulated gene expression and reduced growth of HCC cells in culture and xenografts of HCC tumors, suggesting that inhibition of PJA1 may be beneficial in treating HCC or preventing HCC development in at-risk patients.Significance: These findings provide a novel mechanism regulating the tumor suppressor function of TGFβ in liver carcinogenesis.

Supplementary Figures and legends

Gene numbers regulated by PJA1 knockdown and TGF-β1 treatment

Genetic risk factors are important contributors to the development of colorectal cancer. Following the definition of a linkage signal at 9q22-31, we fine mapped this region in an independent collection of colon cancer families. We used a custom array of single-nucleotide polymorphisms (SNP) densely spaced across the candidate region, performing both single-SNP and moving-window association analyses to identify a colon neoplasia risk haplotype. Through this approach, we isolated the association effect to a five-SNP haplotype centered at 98.15 Mb on chromosome 9q. This haplotype is in strong linkage disequilibrium with the haplotype block containing HABP4 and may be a surrogate for the effect of this CD30 Ki-1 antigen. It is also in close proximity to GALNT12, also recently shown to be altered in colon tumors. We used a predictive modeling algorithm to show the contribution of this risk haplotype and surrounding candidate genes in distinguishing between colon cancer cases and healthy controls. The ability to replicate this finding, the strength of the haplotype association (odds ratio, 3.68), and the accuracy of our prediction model (∼60%) all strongly support the presence of a locus for familial colon cancer on chromosome 9q. Cancer Res; 70(13); 5409–18. ©2010 AACR.

Supplementary Table 1 from Confirmation of Linkage to and Localization of Familial Colon Cancer Risk Haplotype on Chromosome 9q22

Objective: To compare the incidence of and adjusted hazard ratios for common cardiometabolic diseases, musculoskeletal disorders, and psychological morbidities among adults with and without multiple sclerosis (MS). Patients and Methods: Beneficiaries were included if they had an International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic code for MS (n=9815) from a national private insurance claims database (Clinformatics Data Mart; OptumInsight). Adults without MS were also included (n=1,474,232) as a control group. Incidence estimates of common cardiometabolic diseases, musculoskeletal disorders, and psychological morbidities were compared at 5 years of continuous enrollment. Survival models were used to quantify unadjusted and adjusted hazard ratios for incident morbidities. Results: Adults with MS had a higher incidence of any common cardiometabolic disease (51.6% [2663 of 5164] vs 36.4% [328,690 of 904,227]), musculoskeletal disorder (68.8% [3411 of 4959] vs 47.5% [512,422 of 1,077,737]), and psychological morbidity (49.4% [3305 of 6691] vs 30.8% [380,893 of 1,235,388]) than adults without MS, and differences were clinically meaningful (all P

Longitudinal cohort study of privately insured beneficiaries with and without traumatic spinal cord injury (SCI).Compare the incidence of and adjusted hazards for psychological morbidities among adults with and without traumatic SCI, and examine the effect of chronic centralized and neuropathic pain on outcomes.Privately insured beneficiaries were included if they had an ICD-9-CM diagnostic code for traumatic SCI (n = 9081). Adults without SCI were also included (n = 1,474,232).Incidence of common psychological morbidities were compared at 5-years of enrollment. Survival models were used to quantify unadjusted and adjusted hazard ratios for incident psychological morbidities.Adults with SCI had a higher incidence of any psychological morbidity (59.1% vs. 30.9%) as compared to adults without SCI, and differences were to a clinically meaningful extent. Survival models demonstrated that adults with SCI had a greater hazard for any psychological morbidity (HR: 1.67; 95%CI: 1.61, 1.74), and all but one psychological disorder (impulse control disorders), and ranged from HR: 1.31 (1.24, 1.39) for insomnia to HR: 2.10 (1.77, 2.49) for post-traumatic stress disorder. Centralized and neuropathic pain was associated with all psychological disorders, and ranged from HR: 1.31 (1.23, 1.39) for dementia to HR: 3.83 (3.10, 3.68) for anxiety.Adults with SCI have a higher incidence of and risk for common psychological morbidities, as compared to adults without SCI. Efforts are needed to facilitate the development of early interventions to reduce risk of chronic centralized and neuropathic pain and psychological morbidity onset/progression in this higher risk population.

Objective Traumatic spinal cord injury (TSCI) is a life altering event most often causing permanent physical disability. Little is known about the risk of developing Alzheimer disease and related dementia (ADRD) among middle-aged and older adults living with TSCI. Time to diagnosis of and adjusted hazard for ADRD was assessed. Design Cohort study. Setting Using 2007-2017 claims data from the Optum Clinformatics Data Mart, we identified adults (45+) with diagnosis of TSCI (n=7019). Adults without TSCI diagnosis were included as comparators (n=916,516). Using age, sex, race/ethnicity, cardiometabolic, psychological, and musculoskeletal chronic conditions, US Census division, and socioeconomic variables, we propensity score matched persons with and without TSCI (n=6083). Incidence estimates of ADRD were compared at 4 years of enrollment. Survival models were used to quantify unadjusted, fully adjusted, and propensity-matched unadjusted and adjusted hazard ratios (HRs) for incident ADRD. Participants Adults with and without TSCI (N=6083). Intervention Not applicable. Main Outcomes Measures Diagnosis of ADRD. Results Both middle-aged and older adults with TSCI had higher incident ADRD compared to those without TSCI (0.5% vs 0.2% and 11.7% vs 3.3% among 45-64 and 65+ y old unmatched cohorts, respectively) (0.5% vs 0.3% and 10.6% vs 6.2% among 45-64 and 65+ y old matched cohorts, respectively). Fully adjusted survival models indicated that adults with TSCI had a greater hazard for ADRD (among 45-64y old: unmatched HR: 3.19 [95% confidence interval, 95% CI, 2.30-4.44], matched HR: 1.93 [95% CI, 1.06-3.51]; among 65+ years old: unmatched HR: 1.90 [95% CI, 1.77-2.04], matched HR: 1.77 [1.55-2.02]). Conclusions Adults with TSCI are at a heightened risk for ADRD. Improved clinical screening and early interventions aiming to preserve cognitive function are of paramount importance for this patient cohort.

The current global platelet supply is often insufficient to meet all the transfusion needs of patients, in particular for those with alloimmune thrombocytopenia. To address this issue, we have developed a strategy employing a combination of approaches to achieve more efficient production of functional megakaryocytes (MKs) and platelets collected from cord blood (CB)-derived CD34+ hematopoietic cells. This strategy is based on ex-vivo expansion and differentiation of MKs in the presence of bone marrow niche-mimicking mesenchymal stem cells (MSCs), together with two other key components: (1) To enhance MK polyploidization, we used the potent pharmacological Rho-associated coiled-coil kinase (ROCK) inhibitor, KD045, resulting in liberation of increased numbers of functional platelets both in-vitro and in-vivo; (2) To evade HLA class I T-cell-driven killing of these expanded MKs, we employed CRISPR-Cas9-mediated β-2 microglobulin (β2M) gene knockout (KO). We found that coculturing with MSCs and MK-lineage-specific cytokines significantly increased MK expansion. This was further increased by ROCK inhibition, which induced MK polyploidization and platelet production. Additionally, ex-vivo treatment of MKs with KD045 resulted in significantly higher levels of engraftment and donor chimerism in a mouse model of thrombocytopenia. Finally, β2M KO allowed MKs to evade killing by allogeneic T-cells. Overall, our approaches offer a novel, readily translatable roadmap for producing adult donor-independent platelet products for a variety of clinical indications.

BACKGROUND Individuals living with cerebral palsy or spina bifida are at heightened risk for a number of chronic health conditions, such as secondary comorbidities, that may develop or be influenced by the disability, the presence of impairment, and/or the process of aging. However, very little is known about the prevalence and/or risk of developing secondary comorbidities among individuals living with cerebral palsy or spina bifida throughout adulthood. The objective of this study was to compare the prevalence of psychological, cardiometabolic, and musculoskeletal morbidity and multimorbidity among adults with and without cerebral palsy or spina bifida. METHODS Privately insured beneficiaries were included if they had an International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic code for cerebral palsy or spina bifida (n = 29,841). Adults without cerebral palsy or spina bifida were also included (n = 5,384,849). Prevalence estimates of common psychological, cardiometabolic, and musculoskeletal morbidity and multimorbidity (≥2 conditions) were compared. RESULTS Adults living with cerebral palsy or spina bifida had a higher prevalence of all psychological disorders and psychological multimorbidity (14.6% vs. 5.4%), all cardiometabolic disorders and cardiometabolic multimorbidity (22.4% vs. 15.0%), and all musculoskeletal disorders and musculoskeletal multimorbidity (12.2% vs. 5.4%), as compared with adults without cerebral palsy or spina bifida, and differences were to a clinically meaningful extent. CONCLUSIONS Adults with cerebral palsy or spina bifida have a significantly higher prevalence of common psychological, cardiometabolic, and musculoskeletal morbidity and multimorbidity, as compared with adults without cerebral palsy or spina bifida. Efforts are needed to facilitate the development of improved clinical screening algorithms and early interventions to reduce risk of disease onset/progression in these higher risk populations. TO CLAIM CME CREDITS Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME. CME OBJECTIVES Upon completion of this article, the reader should be able to: (1) List the main categories of morbidity that present with higher risk in adults with cerebral palsy and spina bifida; (2) Discuss the potential impact of multimorbidity on 'early aging' in adults living with cerebral palsy and spina bifida; and (3) Describe challenges that adults with cerebral palsy and spina bifida have in obtaining appropriate health care to address prevention and treatment of multimorbidity. LEVEL Advanced. ACCREDITATION The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Individuals with multiple sclerosis (MS) report barriers to accessing care, including receipt of preventive services. Potentially preventable hospitalization (PPH) is an important marker for access to, and receipt of timely care. However, few national studies have examined PPH risk in people with MS or considered the role of preventive care in reducing PPH risk among this patient population. Our objective was to examine PPH risk among adults with MS compared with their counterparts without MS.Optum® Clinformatics® Data Mart (2007-2017) was used to identify 6198 individuals with an MS diagnosis and their propensity-score matched counterparts without MS. Diagnostic and procedural codes were used to identify the presence of preventive hospitalizations, which were defined as quality indicators by the Agency for Healthcare Research and Quality (AHRQ) during the 4-year follow-up period since the diagnosis of MS. Information on receipt of preventive services and office visits was also extracted. Adjusted generalized estimating equations were used to examine the association between MS diagnosis and PPHs. To examine the role of preventive services on odds of PPH amongst people with MS, we reported the adjusted marginal odds ratio (OR) and 95% confidence intervals (CI).The rate of any PPH among people with MS was double that of those without MS (131.6 vs 62.5 per 10,000). We identified higher odds of specific PPH indicators among people with MS compared to those without. Individuals with MS had 65% higher odds of hospitalization for pneumonia (OR=1.65, 95% CI: 1.01, 2.30), with similar significant findings observed for urinary tract infections (OR=4.90, 95% CI: 2.51, 9.57). In MS patients, receipt of preventive services, namely cholesterol screening (OR=0.76, 95% CI: 0.60, 0.95) and annual wellness visits were associated with lower odds of any PPH (OR=0.57, 95% CI: 0.43, 0.76).People with MS were at a higher risk for PPHs compared with their counterparts without MS. Use of appropriate preventive services reduced the risk of PPH among the general population and among those with MS. More efforts are needed to encourage and facilitate the use of preventive care among people with MS. Receipt of timely and appropriate preventive care in this population may reduce the risk for PPH.

Background: Capsule endoscopy (CE) is an emerging tool in the diagnosis and management of occult bleeding and overt obscure gastrointestinal bleeding (OOGIB). Maximizing efficiency of CE can lead to rapid bleeding localization and shorter time to therapy. We investigated whether a trained registered nurse (RN) can accurately interpret bleeding by CE in real time by measuring inter-observer agreement between RN and physician interpretation. Methods: We conducted a prospective study of patients admitted for OOGIB who underwent live-view capsule endoscopy (LVCE) between 12/2016 and 11/2017. A match control group who underwent standard CE was obtained through retrospective review. An RN received a 2-day training program for CE interpretation. RN bedside interpretation for bleeding was followed by interpretation by 2 GI physicians blinded to LVCE findings. Outcomes were compared between groups using t-tests and chi-square tests. Cohen’s kappa measured agreement between physician and RN. Results: Ten subjects were in the LVCE group, and 12 subjects were in the standard of care group. The agreement between the physicians and RNs was 9/10 (90%) with a kappa of 0.73 (95% CI: 0.26-1.00; p=0.016). Patients in the LVCE group had shorter duration to physician interpretation (0.6 vs 0.7 days (p=0.50), duration to endoscopy (1.8 days vs 3 days (p=0.240) and length of stay (8.1 vs. 11.4 days (p=0.26) compared to the standard of care group. Conclusion: This study utilizing an RN for LVCE interpretation found interobserver agreement between RN and physician findings. Larger studies are needed to assess whether this RN-physician team approach can translate to improved outcomes.

Medical insurance claims are becoming increasingly common data sources to answer a variety of questions in biomedical research. Although comprehensive in terms of longitudinal characterization of disease development and progression for a potentially large number of patients, population-based inference using these datasets require thoughtful modifications to sample selection and analytic strategies relative to other types of studies. Along with complex selection bias and missing data issues, claims-based studies are purely observational, which limits effective understanding and characterization of the treatment differences between groups being compared. All these issues contribute to a crisis in reproducibility and replication of comparative findings using medical claims. This paper offers practical guidance to the analytical process, demonstrates methods for estimating causal treatment effects with propensity score methods for several types of outcomes common to such studies, such as binary, count, time to event and longitudinally-varying measures, and also aims to increase transparency and reproducibility of reporting of results from these investigations. We provide an online version of the paper with readily implementable code for the entire analysis pipeline to serve as a guided tutorial for practitioners. The online version can be accessed at https://rydaro.github.io/. The analytic pipeline is illustrated using a sub-cohort of patients with advanced prostate cancer from the large Clinformatics TM Data Mart Database (OptumInsight, Eden Prairie, Minnesota), consisting of 73 million distinct private payer insurees from 2001-2016.

Background Zygapophyseal (facet) joint interventions are the second most common interventional procedure in pain medicine. Opioid exposure after surgery is a significant risk factor for chronic opioid use. The aim of this study was to determine the incidence of new persistent use of opioids after lumbar facet radiofrequency ablation and to assess the effect of postprocedural opioid prescribing on the development of new persistent opioid use. Methods The authors conducted a retrospective cohort study using claims from the Clinformatics Data Mart Database (OptumInsight, USA) to identify opioid-naïve patients between 18 and 64 yr old who had lumbar radiofrequency ablation. Patients who had either subsequent radiofrequency ablation 15 to 180 days or subsequent surgery within 180 days after the primary procedure were excluded from the analysis. The primary outcome was new persistent opioid use, defined as opioid prescription fulfillment within the 8 to 90 and 91 to 180 day periods after radiofrequency ablation. The authors then assessed patient-level risk factors for new persistent opioid use. Results A total of 2,887 patients met the inclusion criteria. Of those patients, 2,277 (78.9%) had radiofrequency ablation without a perioperative opioid fill, and 610 (21.1%) patients had the procedure with a perioperative opioid fill. The unadjusted rate of new persistent opioid use was 5.6% (34 patients) in the group with a perioperative opioid fill versus 2.8% (63 patients) for those without an opioid fill. Periprocedural opioid prescription fill was independently associated with increased odds of new persistent use (adjusted odds ratio, 2.35; 95% CI, 1.51 to 3.66; P < 0.001). Conclusions Periprocedural opioid use after lumbar radiofrequency ablation was associated with new persistent use in previously opioid-naïve patients, suggesting that new exposure to opioids is an independent risk factor for persistent use in patients having radiofrequency ablation for chronic back pain. Opioid prescribing after radiofrequency ablation should be reevaluated and likely discontinued in this population. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Surgical resection is the only cure for neuroendocrine tumors (NETs). However, widespread metastases have already occured by the time of initial diagnosis in many cases making complete surgical removal impossible. We developed a recombinant heavy-chain receptor binding domain (rHCR) of botulinum neurotoxin type A that can specifically target synaptic vesicle 2 (SV2), a surface receptor abundantly expressed in multiple neuroendocrine tumors. Expression of neuroendocrine differentiation markers chromogranin A (CgA) and achaete-scute complex 1 (ASCL1) were signficantly reduced when treated with rHCR. rHCR conjugated to the antimitotic agent monomethyl auristatin E (MMAE) significantly suppressed proliferation of pancreatic carcinoid (BON) and medullary thyroid cancer cells (MZ) at concentrations of 500 and 300 nM respectively, while no growth suppression was observed in pulmonary fibroblasts and cortical neuron control cell lines. In vivo, rHCR-MMAE significantly reduced tumor volume in mouse xenografts with no observed adverse effects. These data suggest recombinant HCR (rHCR) of BoNT/A preferentially targets neuroendocrine cancer without the neurotoxicity of the full BoNT/A and that SV2 is a specific and promising target for delivering drugs to neuroendocrine tumors.

Purpose This technical note presents an inexpensive tool and method for determining lead equivalency using digital radiography x‐ray equipment. Methods A test tool was developed using commercially available lead tape (3M™ Lead Foil Tape 421). The test tool consisted of nine varying lead thick squares arranged in a larger square (0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, and 1.0 mm). It was imaged on a DR plate with a digital portable x‐ray unit across a range of energies (60–120 kVp) and two beam filtrations. Lead equivalency was determined by using the linear relationship between dose to the detector and pixel values in the raw images. The lead equivalency of the tape was validated using known lead thicknesses (physically measured with caliper). Additional lead equivalency measurements were made for protective eyewear, a thyroid shield, and a lead apron. Results The test tool and method measured the two known lead thicknesses to be –9.7% to 7.1% different from the actual values across the range of energies under normal x‐ray beam conditions and under a 1‐mm copper filtered x‐ray beam. The additional lead equivalency measurements of radiation protection apparel across energies ranged from –6% to 20% for both beam conditions when compared with the values provided by the manufacturer. Conclusion This work validates the test tool and methodology as an inexpensive alternative to checking the lead equivalency of radiation protection apparel in a clinical setting. The methodology is equipment independent with a few prerequisites.

Modern fluoroscopes used for image guidance have become quite complex. Adding to this complexity are the many regulatory and accreditation requirements that must be fulfilled during acceptance testing of a new unit. Further, some of these acceptance tests have pass/fail criteria, whereas others do not, making acceptance testing a subjective and time-consuming task. The AAPM Task Group 272 Report spells out the details of tests that are required and gives visibility to some of the tests that while not yet required are recommended as good practice. The organization of the report begins with the most complicated fluoroscopes used in interventional radiology or cardiology and continues with general fluoroscopy and mobile C-arms. Finally, the appendices of the report provide useful information, an example report form and topics that needed their own section due to the level of detail.

The aim of the study was to estimate organ dose rate reduction to a female anthropomorphic phantom, which simulated the cardiologist, during percutaneous coronary interventions (PCI) when the patient’s arm support was covered with 0.4-mm lead foil. Organ dose rates were determined using five radiation detectors inserted into the left eye, left thyroid, left breast, left liver lobe and uterus of the phantom. A male anthropomorphic phantom was placed on the examination table of an angiography system. Heart images of the patient phantom were acquired under 10 gantry angulations typical for PCI. The lead-covered arm support did not interfere with any of the cardiac images. The median organ dose rate reductions to the left eye, left thyroid, left breast, left liver lobe and uterus were 7.8, 36.0, 28.8, 35.7 and 33.5%, respectively. The lead-covered arm support substantially reduced scattered radiation to the female cardiologist without interfering with clinical environments.

In this article, we review automatic brightness control (ABC) for fluoroscopy imaging systems. Starting from the simple manual control, the discussion is extended to the kV-primary ABC system, and then to the most recent contrast-to-noise ratio optimized (CNR Optimized) automatic dose rate control system (ADRC). The nature of this review article is trifold. First, it describes the ABC/ADRC and associated circuits governing the operation of the fluoroscopy imaging chain. Second, we show the characteristics of a control logic from a radiation physics point of view. Third, we introduce the most recent activities in the evaluation of CNR-optimized fluoroscopy systems and the phantom design that would be compatible with the design concept of the ADRC. Because of these three subject items in the discussion process, this article is also educational in nature written for medical physicists and radiological technologists who might be less familiar with the design concept of fluoroscopy operation, specifically on the ABC and ADRC. We insert a few related matters associated with fluoroscopy automatic control circuits where they seem applicable and appropriate to enhance the understanding of fluoroscopy operation logic.

Adverse childhood experiences (ACEs) are linked to poor health outcomes; however, the relationship between ACEs and health outcomes among children and adolescents with sickle cell disease (SCD) has limited documentation in the published literature.This retrospective cohort study involved 45 children and 30 adolescents. Participants were screened using the Center for Youth Wellness ACE Questionnaire. Parents completed the questionnaire for children. Adolescents provided self-report. ACEs were treated as continuous and categorical scales: 0-1 verus ≥2 original ACEs (individual and/or familial level); 0-1 versus ≥2 additional ACEs (community level); and 0-3 versus ≥4 expanded ACEs (original + additional). Pain and acute chest syndrome events were compared using Wilcoxon rank-sum tests, and correlated with cumulative ACE scores using Spearman's correlation. Multivariable models were fitted to examine the association between ACEs and pain/acute chest syndrome.The cumulative number of original ACEs positively correlated with acute chest syndrome events (rho = .53, p = .003) and pain (rho = .40, p = .028) among adolescents. Adolescents with ≥2 versus 0-1 original ACEs had a higher number of acute chest syndrome events (4.9 ± 2.6 vs. 1.6 ± 2.2, p = .002); however, this association was confounded by asthma. Acute chest syndrome events and hospitalizations for pain did not differ among child ACE groups. Emergency department (ED) pain visits were higher among children with ≥4 versus 0-3 expanded ACEs (1.6 ± 2.8 vs. 3.3 ± 3.2, p = .042), even after controlling for SCD genotype, asthma, disease-modifying treatment, and follow-up years (p = .027).ACEs are linked to increased morbidity among children and adolescents with SCD. Prospective studies are needed to further understand this relationship and test ACE-protective remedies.

Aim To examine the risk of Alzheimer disease and related dementia (ADRD) among adults with cerebral palsy (CP). Method Using administrative insurance claims data for 2007 to 2017 in the USA, we identified adults (45y or older) with a diagnosis of CP (n=5176). Adults without a diagnosis of CP were included as a typically developing comparison group (n=1 119 131). Using age, sex, ethnicity, other demographic variables, and a set of chronic morbidities, we propensity-matched individuals with and without CP (n=5038). Cox survival models were used to estimate ADRD risk within a 3-year follow up. Results The unadjusted incidence of ADRD was 9 and 2.4 times higher among cohorts of adults 45 to 64 years (1.8%) and 65 years and older (4.8%) with CP than the respective unmatched individuals without CP (0.2% and 2.0% among 45-64y and 65y or older respectively). Fully adjusted survival models indicated that adults with CP had a greater hazard for ADRD (among 45-64y: unmatched hazard ratio 7.48 [95% confidence interval {CI} 6.05-9.25], matched hazard ratio 4.73 [95% CI 2.72-8.29]; among 65y or older: unmatched hazard ratio 2.21 [95% CI 1.95-2.51], matched hazard ratio 1.73 [1.39-2.15]). Interpretation Clinical guidelines for early screening of cognitive function among individuals with CP need updating, and preventative and/or therapeutic services should be used to reduce the risk of ADRD.

This study was conducted to determine the association between fluid balance metrics and mortality and other postoperative outcomes after neonatal cardiac operation in a contemporary multicenter cohort.This was an observational cohort study across 22 hospitals in neonates (≤30 days) undergoing cardiac operation. We explored overall percentage fluid overload, postoperative day 1 percentage fluid overload, peak percentage fluid overload, and time to first negative daily fluid balance. The primary outcome was in-hospital mortality. Secondary outcomes included postoperative duration of mechanical ventilation and intensive care unit (ICU) and hospital length of stay. Multivariable logistic or negative binomial regression was used to determine independent associations between fluid overload variables and each outcome.The cohort included 2223 patients. In-hospital mortality was 3.9% (n = 87). Overall median peak percentage fluid overload was 4.9% (interquartile range, 0.4%-10.5%). Peak percentage fluid overload and postoperative day 1 percentage fluid overload were not associated with primary or secondary outcomes. Hospital resource utilization increased on each successive day of not achieving a first negative daily fluid balance and was characterized by longer duration of mechanical ventilation (incidence rate ratio, 1.11; 95% CI, 1.08-1.14), ICU length of stay (incidence rate ratio, 1.08; 95% CI, 1.03-1.12), and hospital length of stay (incidence rate ratio, 1.09; 95% CI, 1.05-1.13).Time to first negative daily fluid balance, but not percentage fluid overload, is associated with improved postoperative outcomes in neonates after cardiac operation. Specific treatments to achieve an early negative fluid balance may decrease postoperative care durations.

Introduction:Six treatments have improved overall survival in men with metastatic castration resistant prostate cancer, each differing in toxicities and cost. We identified patient and prov...

PURPOSE To determine if surface treatment and cement selection for traditional 3 mol% yttria partially stabilized zirconia (3Y-PSZ), "translucent" 5 mol% yttria-stabilized zirconia (5Y-Z), or lithium disilicate crowns affected their fracture load. MATERIALS AND METHODS Crowns with 0.8 mm uniform thickness (96, n = 8/group) were milled of 3Y-PSZ (Lava Plus), 5Y-Z (Lava Esthetic), or lithium disilicate (e.max CAD) and sintered/crystallized. Half the crowns were either particle-abraded with 30 µm alumina (zirconias) or etched with 5% hydrofluoric acid (lithium disilicate), and the other half received no surface treatment. Half the crowns from each group were luted with resin-modified glass ionomer (RMGI, RelyX Luting Plus) and half were luted with a resin cement (RelyX Unicem 2) to resin composite dies. Crowns were load cycled (100,000 cycles, 100 N force, 24°C water) and then loaded with a steel indenter until failure. A three-way ANOVA examined the effects of material, cement, and surface treatment on fracture load. Post-hoc comparisons were performed with the Tukey-Krammer method. RESULTS Fracture load was signficiantly different for materials and cements (p

The Image Gently® campaign was launched by several radiological societies in 2007 to promote safe imaging in children. A goal of the campaign was to reduce ionizing radiation exposure in children. Given the recurrent nature of kidney stones, affected children are at risk for unnecessary ionizing radiation exposure from computerized tomography. We sought to determine whether the Image Gently campaign led to a decrease in the use of computerized tomography for evaluating children with nephrolithiasis. We hypothesized that the campaign was the primary cause of a reduction in the use of computerized tomography.We analyzed medical claims data from 2001 to 2015 identifying children with nephrolithiasis covered by the same commercial insurance provider. Using a difference in differences design, we estimated changes in computerized tomography use after the campaign started among patients less than 18 years old compared to a control group age 18 years or older with nephrolithiasis.We identified 12,734 children and 787,720 adults diagnosed with nephrolithiasis. Before 2007 quarterly rates of computerized tomography use during a stone episode (per 1,000 patients) were increasing at a parallel rate in children and adults (5.1 in children vs 7.2 in adults, p = 0.123). After the Image Gently campaign started the use of computerized tomography decreased in both groups but at a slightly higher rate in adults (difference in differences 2.96, 95% CI 0.00 to 5.91, p = 0.050).Although there has been a reduction in the use of computerized tomography among children with nephrolithiasis, given a similar trend seen in adults this change cannot be primarily attributed to the Image Gently campaign.

Background Several countries have regionalized congenital heart surgery (CHS). Before considering regionalization in the US, the current landscape must be understood. This investigation characterized the network of US hospitals providing CHS, including hospital locations and patient travel patterns. Methods Patients ≤18 years undergoing CHS were identified in 2012 State Inpatient Databases from 39 states. Cases were stratified by the RACHS-1 method (high-risk defined as RACHS-1 categoris 4 to 6). Hospital and patient locations were identified. Patients were mapped to hospitals where they underwent surgery. Results A total of 153 hospitals across 36 states performed ≥1 RACHS-1 case (19,064 operations). Of these, 101 hospitals (66%) were located within 25 miles of another hospital. Median annual RACHS-1 case volume was 90 (range, 1 to 797), with 55 hospitals performing ≤50 cases. A total of 111 hospitals (73%) performed ≥1 high-risk case. Of these, 39 (35%) performed ≤10 high-risk cases/year. Overall mortality rate was 3.5% (n = 666), with risk-adjusted mortality being lowest at hospitals in the highest-volume quartile (≥150 cases/year). About 25% of patients (n = 4,012) traveled >100 miles, with most traveling to hospitals within the highest-volume quartile; 53% of patients (n = 8,376) bypassed the nearest CHS hospital. Mortality was not associated with travel distance. Conclusions We identified more US hospitals performing CHS than has been previously described. Many are small-volume and are in close proximity to one another. Patients are already traveling long distances to hospitals within the highest-volume quartile. These data help define the current landscape of CHS and associated considerations regarding regionalization.

This work explores the current performance and scaling of a fully-implicit stabilized unstructured finite element (FE) variational multiscale (VMS) capability for large-scale simulations of 3D incompressible resistive magnetohydrodynamics (MHD). The large-scale linear systems that are generated by a Newton nonlinear solver approach are iteratively solved by preconditioned Krylov subspace methods. The efficiency of this approach is critically dependent on the scalability and performance of the algebraic multigrid preconditioner. This study considers the performance of the numerical methods as recently implemented in the second-generation Trilinos implementation that is 64-bit compliant and is not limited by the 32-bit global identifiers of the original Epetra-based Trilinos. The study presents representative results for a Poisson problem on 1.6 million cores of an IBM Blue Gene/Q platform to demonstrate very large-scale parallel execution. Additionally, results for a more challenging steady-state MHD generator and a transient solution of a benchmark MHD turbulence calculation for the full resistive MHD system are also presented. These results are obtained on up to 131,000 cores of a Cray XC40 and one million cores of a BG/Q system.