Publications by authors named "David C Johnson"

214 Publications

Association Between Graft Choice and 6-Year Outcomes of Revision Anterior Cruciate Ligament Reconstruction in the MARS Cohort.

Am J Sports Med 2021 Aug 14;49(10):2589-2598. Epub 2021 Jul 14.

University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Background: Although graft choice may be limited in the revision setting based on previously used grafts, most surgeons believe that graft choice for anterior cruciate ligament (ACL) reconstruction is an important factor related to outcome.

Hypothesis: In the ACL revision setting, there would be no difference between autograft and allograft in rerupture rate and patient-reported outcomes (PROs) at 6-year follow-up.

Study Design: Cohort study; Level of evidence, 2.

Methods: Patients who had revision surgery were identified and prospectively enrolled in this cohort study by 83 surgeons over 52 sites. Data collected included baseline characteristics, surgical technique and pathology, and a series of validated PRO measures. Patients were followed up at 6 years and asked to complete the identical set of PRO instruments. Incidence of additional surgery and reoperation because of graft failure were also recorded. Multivariable regression models were used to determine the predictors (risk factors) of PROs, graft rerupture, and reoperation at 6 years after revision surgery.

Results: A total of 1234 patients including 716 (58%) men were enrolled. A total of 325 (26%) underwent revision using a bone-patellar tendon-bone (BTB) autograft; 251 (20%), soft tissue autograft; 289 (23%), BTB allograft; 302 (25%), soft tissue allograft; and 67 (5%), other graft. Questionnaires and telephone follow-up for subsequent surgery information were obtained for 809 (66%) patients, while telephone follow-up was only obtained for an additional 128 patients for the total follow-up on 949 (77%) patients. Graft choice was a significant predictor of 6-year Marx Activity Rating Scale scores ( = .024). Specifically, patients who received a BTB autograft for revision reconstruction had higher activity levels than did patients who received a BTB allograft (odds ratio [OR], 1.92; 95% CI, 1.25-2.94). Graft rerupture was reported in 5.8% (55/949) of patients by their 6-year follow-up: 3.5% (16/455) of patients with autografts and 8.4% (37/441) of patients with allografts. Use of a BTB autograft for revision resulted in patients being 4.2 times less likely to sustain a subsequent graft rupture than if a BTB allograft were utilized ( = .011; 95% CI, 1.56-11.27). No significant differences were found in graft rerupture rates between BTB autograft and soft tissue autografts ( = .87) or between BTB autografts and soft tissue allografts ( = .36). Use of an autograft was found to be a significant predictor of having fewer reoperations within 6 years compared with using an allograft ( = .010; OR, 0.56; 95% CI, 0.36-0.87).

Conclusion: BTB and soft tissue autografts had a decreased risk in graft rerupture compared with BTB allografts. BTB autografts were associated with higher activity level than were BTB allografts at 6 years after revision reconstruction. Surgeons and patients should consider this information when choosing a graft for revision ACL reconstruction.
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http://dx.doi.org/10.1177/03635465211027170DOI Listing
August 2021

Substituent Effects in the Synthesis of Heterostructures.

Inorg Chem 2021 Jul 16;60(13):9598-9606. Epub 2021 Jun 16.

Department of Chemistry and Materials Science Institute, University of Oregon, Eugene, Oregon 97403, United States.

There have been a number of surprising reports of unexpected products when preparing heterostructures of BiSe with other 2D layers. These reports prompted us to explore the formation of metastable heterostructures containing BiSe using X-ray diffraction techniques to follow the reaction pathway. We discovered that the products formed depend on the electronic properties of the second constituent. Bi|Se layers deposited in a 2:3 ratio with enough atoms to make a single five-plane layer evolved to form thermodynamically stable BiSe as expected from the phase diagram. When the same Bi|Se layers were sequentially deposited with M|Se layers that form semiconductor layers (PbSe and 2H-MoSe), BiSe-containing heterostructures formed. When the same Bi|Se layers were deposited with M|Se layers that form metallic layers (TiSe VSe, and 1T-MoSe), BiSe-containing heterostructures formed. The amount of excess Se in the precursor controls whether [(BiSe)][(MoSe)] or [(BiSe)][(MoSe)] forms. XPS data indicates that a mixture of both metallic 1T and semiconducting 2H-MoSe is present in [(BiSe)][(MoSe)], while only semiconducting 2H-MoSe is present when layered with BiSe. The electronic structure of adjacent layers impacts the formation of different structures from layers with similar local compositions. This provides an important additional parameter to consider when designing the synthesis of heterostructures, similar to substituent effects in molecular chemistry.
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http://dx.doi.org/10.1021/acs.inorgchem.1c00811DOI Listing
July 2021

Improving Shared Decision Making in Latino Men With Prostate Cancer: A Thematic Analysis.

MDM Policy Pract 2021 Jan-Jun;6(1):23814683211014180. Epub 2021 May 27.

Department of Marketing, Shidler College of Business, University of Hawai'i, Honolulu, Hawai'i.

Multiple studies have shown that digitally mediated decision aids help prepare patients for medical decision making with their providers. However, few studies have investigated whether decision-support preferences differ between non-English-speaking and English-speaking Latino men with limited literacy. To identify and compare health information seeking patterns, preferences for information presentation, and interest in digital decision aids in a sample of Southern Californian underserved Latino men with newly diagnosed prostate cancer at a county hospital. We conducted semistructured, in-depth telephone interviews with 12 Spanish-speaking and 8 English-speaking Latino men using a purposive sampling technique. Following transcription of taped interviews, Spanish interviews were translated. Using a coding protocol developed by the team, two bilingual members jointly analyzed the transcripts for emerging themes. Coder agreement exceeded 80%. Differences were resolved through discussion. Thematic differences between groups with different preferred languages emerged. Most respondents engaged in online health information seeking using cellphones, perceived a paternalistic patient-provider relationship, and expressed willingness to use hypothetical digital decision aids if recommended by their provider. English speakers reported higher digital technology proficiency for health-related searches. They also more frequently indicated family involvement in digital search related to their condition and preferred self-guided, web-based decision aids. In comparison, Spanish speakers reported lower digital technology proficiency and preferred family-involved, coach-guided, paper and visual decision aids. English speakers reported substantially higher levels of formal education. Preferences regarding the use of digital technology to inform prostate cancer treatment decision making among underserved Latino men varied depending on preferred primary language. Effective preparation of underserved Latino men for shared decision making requires consideration of alternative approaches depending on level of education attainment and preferred primary language.
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http://dx.doi.org/10.1177/23814683211014180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165846PMC
May 2021

Anterograde transport of α-herpesviruses in neuronal axons.

Virology 2021 Jul 4;559:65-73. Epub 2021 Mar 4.

Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, OR, 97239, USA. Electronic address:

α-herpesviruses have been very successful, principally because they establish lifelong latency in sensory ganglia. An essential piece of the lifecycle of α-herpesviruses involves the capacity to travel from sensory neurons to epithelial tissues following virus reactivation from latency, a process known as anterograde transport. Virus particles formed in neuron cell bodies hitchhike on kinesin motors that run along microtubules, the length of axons. Herpes simplex virus (HSV) and pseudorabies virus (PRV) have been intensely studied to elucidate anterograde axonal transport. Both viruses use similar strategies for anterograde transport, although there are significant differences in the form of virus particles transported in axons, the identity of the kinesins that transport viruses, and how certain viral membrane proteins, gE/gI and US9, participate in this process. This review compares the older models for HSV and PRV anterograde transport with recent results, which are casting a new light on several aspects of this process.
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http://dx.doi.org/10.1016/j.virol.2021.02.011DOI Listing
July 2021

Prostate cancer.

Nat Rev Dis Primers 2021 02 4;7(1). Epub 2021 Feb 4.

Cancer Research UK Manchester Institute, University of Manchester, Manchester Cancer Research Centre, Manchester, UK.

Prostate cancer is a complex disease that affects millions of men globally, predominantly in high human development index regions. Patients with localized disease at a low to intermediate risk of recurrence generally have a favourable outcome of 99% overall survival for 10 years if the disease is detected and treated at an early stage. Key genetic alterations include fusions of TMPRSS2 with ETS family genes, amplification of the MYC oncogene, deletion and/or mutation of PTEN and TP53 and, in advanced disease, amplification and/or mutation of the androgen receptor (AR). Prostate cancer is usually diagnosed by prostate biopsy prompted by a blood test to measure prostate-specific antigen levels and/or digital rectal examination. Treatment for localized disease includes active surveillance, radical prostatectomy or ablative radiotherapy as curative approaches. Men whose disease relapses after prostatectomy are treated with salvage radiotherapy and/or androgen deprivation therapy (ADT) for local relapse, or with ADT combined with chemotherapy or novel androgen signalling-targeted agents for systemic relapse. Advanced prostate cancer often progresses despite androgen ablation and is then considered castration-resistant and incurable. Current treatment options include AR-targeted agents, chemotherapy, radionuclides and the poly(ADP-ribose) inhibitor olaparib. Current research aims to improve prostate cancer detection, management and outcomes, including understanding the fundamental biology at all stages of the disease.
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http://dx.doi.org/10.1038/s41572-020-00243-0DOI Listing
February 2021

Enhanced Low-Temperature Thermoelectric Performance in (PbSe)(VSe) Heterostructures due to Highly Correlated Electrons in Charge Density Waves.

Nano Lett 2020 Nov 23;20(11):8008-8014. Epub 2020 Oct 23.

Department of Chemistry, University of Oregon, Eugene, Oregon 97403-1253, United States.

We explore the effect of charge density wave (CDW) on the in-plane thermoelectric transport properties of (PbSe)(VSe) and (PbSe)(VSe) heterostructures. In (PbSe)(VSe) we observe an abrupt 86% increase in the Seebeck coefficient, 245% increase in the power factor, and a slight decrease in resistivity over the CDW transition. This behavior is not observed in (PbSe)(VSe) and is rather unusual compared to the general trend observed in other materials. The abrupt transition causes a deviation from the Mott relationship through correlated electron states. Raman spectra of the (PbSe)(VSe) material show the emergence of additional peaks below the CDW transition temperature associated with VSe material. Temperature-dependent in-plane X-ray diffraction (XRD) spectra show a change in the in-plane thermal expansion of VSe in (PbSe)(VSe) due to lattice distortion. The increase in the power factor and decrease in the resistivity due to CDW suggest a potential mechanism for enhancing the thermoelectric performance at the low temperature region.
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http://dx.doi.org/10.1021/acs.nanolett.0c02882DOI Listing
November 2020

Predicting Pathological Tumor Size in Prostate Cancer Based on Multiparametric Prostate Magnetic Resonance Imaging and Preoperative Findings.

J Urol 2021 02 7;205(2):444-451. Epub 2020 Oct 7.

UCLA Institute of Urologic Oncology, Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, California.

Purpose: Oncologic efficacy of focal therapies in prostate cancer depends heavily on accurate tumor size estimation. We aim to evaluate the agreement between radiologic tumor size and pathological tumor size, and identify predictors of pathological tumor size.

Materials And Methods: This single arm study cohort included all consecutive patients with biopsy proven prostate cancer and a corresponding PI-RADS®v2 3 or greater index tumor on multiparametric magnetic resonance imaging who subsequently underwent radical prostatectomy. Radiologic tumor size was defined as maximum tumor diameter on multiparametric magnetic resonance imaging and compared to whole mount histopathology tumor correlates. The difference between radiologic tumor size and pathological tumor size was assessed, and clinical, pathological and radiographic predictors of pathological tumor size were examined.

Results: A total of 461 consecutive lesions in 441 men were included for statistical analysis. Mean radiologic tumor size and pathological tumor size was 1.57 and 2.37 cm, respectively (p <0.001). Radiologic tumor size consistently underestimated pathological tumor size regardless of the preoperative covariates, and the degree of underestimation increased with smaller radiologic tumor size and lower PI-RADSv2 scores. Pathological tumor size was significantly larger for biopsy Gleason Grade Group (GG) 5 compared to GG1 (mean change 0.37 cm, p=0.014), PI-RADSv2 5 lesions compared to PI-RADSv2 4 (mean change 0.26, p=0.006) and higher prostate specific antigen density. The correlations between radiologic tumor size vs pathological tumor size according to biopsy GG and radiologic covariates were generally low with correlation coefficients ranging between 0.1 and 0.65.

Conclusions: Multiparametric magnetic resonance imaging frequently underestimates pathological tumor size and the degree of underestimation increases with smaller radiologic tumor size and lower PI-RADSv2 scores. Therefore, a larger ablation margin may be required for smaller tumors and lesions with lower PI-RADSv2 scores. These variables must be considered when estimating treatment margins in focal therapy.
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http://dx.doi.org/10.1097/JU.0000000000001389DOI Listing
February 2021

Rate of infection following revision anterior cruciate ligament reconstruction and associated patient- and surgeon-dependent risk factors: Retrospective results from MOON and MARS data collected from 2002 to 2011.

J Orthop Res 2021 02 19;39(2):274-280. Epub 2020 Oct 19.

Bridger Orthopedic and Sports Medicine, Bozeman, Montana, USA.

Infection is a rare occurrence after revision anterior cruciate ligament reconstruction (rACLR). Because of the low rates of infection, it has been difficult to identify risk factors for infection in this patient population. The purpose of this study was to report the rate of infection following rACLR and assess whether infection is associated with patient- and surgeon-dependent risk factors. We reviewed two large prospective cohorts to identify patients with postoperative infections following rACLR. Age, sex, body mass index (BMI), smoking status, history of diabetes, and graft choice were recorded for each patient. The association of these factors with postoperative infection following rACLR was assessed. There were 1423 rACLR cases in the combined cohort, with 9 (0.6%) reporting postoperative infections. Allografts had a higher risk of infection than autografts (odds ratio, 6.8; 95% CI, 0.9-54.5; p = .045). Diabetes (odds ratio, 28.6; 95% CI, 5.5-149.9; p = .004) was a risk factor for infection. Patient age, sex, BMI, and smoking status were not associated with risk of infection after rACLR.
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http://dx.doi.org/10.1002/jor.24871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854959PMC
February 2021

Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography Compared with Conventional Imaging for Initial Staging of Treatment-naïve Intermediate- and High-risk Prostate Cancer: A Retrospective Single-center Study.

Eur Urol Oncol 2020 Sep 18. Epub 2020 Sep 18.

Institute of Urologic Oncology (IUO), Department of Urology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; Ahmanson Translational Imaging Division, Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA; Physics & Biology in Medicine Interdepartmental Graduate Program, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.

Background: The role of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) imaging in the initial staging of men with prostate cancer (PCa) has yet to be evaluated adequately.

Objective: To investigate the concordance of PSMA PET/CT with conventional imaging (CI) with cross-sectional abdominopelvic and/or radionuclide bone imaging in the initial staging of patients with treatment-naïve PCa.

Design, Setting, And Participants: We performed a post hoc retrospective cohort study of patients enrolled in a prospective single-arm trial (NCT03368547). We included patients with intermediate-risk (IR) and high-risk (HR) PCa who underwent PSMA PET/CT within 6 mo of CI. Patients with any treatment prior to PSMA PET/CT were excluded. Patient- and tumor-specific data, and imaging findings were obtained.

Outcome Measurements And Statistical Analysis: Our primary outcome measurement was the concordance rate of PSMA PET/CT with CI for the identification of N, M1a, M1b, and M1c disease. Descriptive statistics were used.

Results And Limitations: A total of 168 patients with treatment-naïve IR and HR PCa met the inclusion criteria. HR disease accounted for 124/168 (73.8%) patients. The median prostate-specific antigen was 11.4 (6.8-24.6)ng/ml. The rates of nonconcordance between PSMA PET/CT and CI were 34/162 (21.0%), 5/70 (7.1%), 8/92 (8.7%), and 1/71 (1.4%) for N, M1a, M1b, and M1c disease, respectively. PSMA PET/CT assigned a higher stage in 37/168 (22.0%) patients and a lower stage in 12/170 (7.1%) patients. In a subset of 50 patients treated with radical prostatectomy and pelvic lymph node dissection, the prevalence of PSMA PET/CT-positive and that of CI-positive nodal disease were 14% and 4%, and the false negative rates were 30% and 32%, respectively. The principal limitations of this study include the heterogeneity in CI modalities and the 6-mo time frame between CI and PSMA PET.

Conclusions: PSMA PET/CT imaging may serve as a valuable tool in the initial staging of treatment-naïve IR and HR PCa.

Patient Summary: We evaluated how prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) compared with standard imaging (such as computed tomography, bone scan, and prostate magnetic resonance imaging) for initial staging of patients with prostate cancer. Our findings suggest that PSMA PET/CT may detect and rule out more metastatic lesions, which could prove valuable in guiding treatment.
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http://dx.doi.org/10.1016/j.euo.2020.08.012DOI Listing
September 2020

Characterization of the Herpes Simplex Virus (HSV) Tegument Proteins That Bind to gE/gI and US9, Which Promote Assembly of HSV and Transport into Neuronal Axons.

J Virol 2020 11 9;94(23). Epub 2020 Nov 9.

Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, Oregon, USA

The herpes simplex virus (HSV) heterodimer gE/gI and another membrane protein, US9, which has neuron-specific effects, promote the anterograde transport of virus particles in neuronal axons. Deletion of both HSV gE and US9 blocks the assembly of enveloped particles in the neuronal cytoplasm, which explains why HSV virions do not enter axons. Cytoplasmic envelopment depends upon interactions between viral membrane proteins and tegument proteins that encrust capsids. We report that tegument protein UL16 is unstable, i.e., rapidly degraded, in neurons infected with a gE-/US9- double mutant. Immunoprecipitation experiments with lysates of HSV-infected neurons showed that UL16 and three other tegument proteins, namely, VP22, UL11, and UL21, bound either to gE or gI. All four of these tegument proteins were also pulled down with US9. In neurons transfected with tegument proteins and gE/gI or US9, there was good evidence that VP22 and UL16 bound directly to US9 and gE/gI. However, there were lower quantities of these tegument proteins that coprecipitated with gE/gI and US9 from transfected cells than those of infected cells. This apparently relates to a matrix of several different tegument proteins formed in infected cells that bind to gE/gI and US9. In cells transfected with individual tegument proteins, this matrix is less prevalent. Similarly, coprecipitation of gE/gI and US9 was observed in HSV-infected cells but not in transfected cells, which argued against direct US9-gE/gI interactions. These studies suggest that gE/gI and US9 binding to these tegument proteins has neuron-specific effects on virus HSV assembly, a process required for axonal transport of enveloped particles. Herpes simplex viruses 1 and 2 and varicella-zoster virus cause significant morbidity and mortality. One basic property of these viruses is the capacity to establish latency in the sensory neurons and to reactivate from latency and then cause disease in peripheral tissues, such as skin and mucosal epithelia. The transport of nascent HSV particles from neuron cell bodies into axons and along axons to axon tips in the periphery is an important component of this reactivation and reinfection. Two HSV membrane proteins, gE/gI and US9, play an essential role in these processes. Our studies help elucidate how HSV gE/gI and US9 promote the assembly of virus particles and sorting of these virions into neuronal axons.
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http://dx.doi.org/10.1128/JVI.01113-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654281PMC
November 2020

Analysis of guideline recommended use of renal mass biopsy and association with treatment.

Can J Urol 2020 08;27(4):10285-10293

Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

Introduction: Renal mass biopsy (RMB) may not be indicated when the results are unlikely to impact management, such as in young and/or healthy patients and in elderly and/or frail patients. We analyzed the utility of RMB in three patient cohorts stratified by age-adjusted Charlson comorbidity index score (ACCI).

Materials And Methods: We identified patients with cT1a renal tumors in the National Cancer Database from 2004-2014. We combined age and Charlson-Deyo scores to identify young and/or healthy patients ('healthy-ACCI'), elderly and/or frail patients ('frail-ACCI'), and a reference cohort. We performed multivariable logistic regression to identify predictors of RMB and treatment. We evaluated the impact of RMB on management by analyzing the proportion of high-grade disease on final pathology as a surrogate for risk stratification.

Results: We identified 36,720 healthy-ACCI, 2,516 frail-ACCI, and 18,989 reference-ACCI patients. Healthy-ACCI patients were less likely to undergo RMB (7.5% versus 10.8%; p < 0.001) while frail-ACCI patients underwent RMB at similar rates (11.8% versus 10.8%; p = 0.14) compared with reference-ACCI patients. On multivariable logistic regression, in both healthy-ACCI and frail-ACCI patients, RMB was associated with decreased odds of surgical treatment, and increased odds of ablation and surveillance (all p < 0.01). In the frail-ACCI patients, higher grade disease at surgery was identified in the RMB cohort (32.9% versus 23.5%, p = 0.05).

Conclusions: RMB is performed less frequently in healthy-ACCI patients compared with the reference cohort. RMB is associated with decreased odds of surgical treatment and increased odds of surveillance and ablation in all cohorts. In frail-ACCI patients who underwent surgery, RMB may provide additional risk stratification as these patients had lower rates of low-grade disease.
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August 2020

Meniscal Repair in the Setting of Revision Anterior Cruciate Ligament Reconstruction: Results From the MARS Cohort.

Am J Sports Med 2020 10 21;48(12):2978-2985. Epub 2020 Aug 21.

All authors are listed in the Authors section at the end of this article.

Background: Meniscal preservation has been demonstrated to contribute to long-term knee health. This has been a successful intervention in patients with isolated tears and tears associated with anterior cruciate ligament (ACL) reconstruction. However, the results of meniscal repair in the setting of revision ACL reconstruction have not been documented.

Purpose: To examine the prevalence and 2-year operative success rate of meniscal repairs in the revision ACL setting.

Study Design: Case-control study; Level of evidence, 3.

Methods: All cases of revision ACL reconstruction with concomitant meniscal repair from a multicenter group between 2006 and 2011 were selected. Two-year follow-up was obtained by phone and email to determine whether any subsequent surgery had occurred to either knee since the initial revision ACL reconstruction. If so, operative reports were obtained, whenever possible, to verify the pathologic condition and subsequent treatment.

Results: In total, 218 patients (18%) from 1205 revision ACL reconstructions underwent concurrent meniscal repairs. There were 235 repairs performed: 153 medial, 48 lateral, and 17 medial and lateral. The majority of these repairs (n = 178; 76%) were performed with all-inside techniques. Two-year surgical follow-up was obtained on 90% (197/218) of the cohort. Overall, the meniscal repair failure rate was 8.6% (17/197) at 2 years. Of the 17 failures, 15 were medial (13 all-inside, 2 inside-out) and 2 were lateral (both all-inside). Four medial failures were treated in conjunction with a subsequent repeat revision ACL reconstruction.

Conclusion: Meniscal repair in the revision ACL reconstruction setting does not have a high failure rate at 2-year follow-up. Failure rates for medial and lateral repairs were both <10% and consistent with success rates of primary ACL reconstruction meniscal repair. Medial tears underwent reoperation for failure at a significantly higher rate than lateral tears.
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http://dx.doi.org/10.1177/0363546520948850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171059PMC
October 2020

Investigating the Formation of MoSe and TiSe Films from Artificially Layered Precursors.

Inorg Chem 2020 Sep 12;59(17):12536-12544. Epub 2020 Aug 12.

Department of Chemistry and Biochemistry, University of Oregon, Eugene, Oregon, United States.

The reaction of ultrathin layers of Mo and Ti with Se was investigated, and significantly different reaction pathways were found. However, in both systems postdeposition annealing results in smooth dichalcogenide films with specific thicknesses determined by the precursor. X-ray diffraction (XRD) patterns of as-deposited Mo|Se films around a 1:2 ratio of Mo to Se contain weak, broad reflections from small and isolated MoSe crystallites that nucleated during deposition and a sharper intensity maximum resulting from the composition modulation created from the alternating deposition of Mo and Se layers. In contrast, as-deposited Ti|Se films around a 1:2 ratio of Ti to Se contain narrow and intense 00 reflections from TiSe crystallites and do not contain a Bragg reflection from the sequence of deposited Ti|Se layers. The as-deposited TiSe crystallites have a larger axis lattice parameter than was previously reported for TiSe, however, which suggests a poor vertical interlayer registry and/or high defect densities including interstitial atoms. In-plane XRD patterns show the nucleation of both TiSe and TiSe during deposition, with the TiSe at the substrate. For both systems, annealing the precursors decreases the peak width and increases the intensity of reflections from crystalline TiSe and MoSe. Optimized films consist of a single phase after the annealing and show clear Laue oscillations in the specular XRD patterns, which can only occur if a majority of the diffracting crystallites in the film consist of the same number of unit cells. The highest quality films was obtained when an excess of ∼10% Se was deposited in the precursor, which presumably acts as a flux to facilitate diffusion of metal atoms to crystallite growth fronts and compensates for Se loss to the open system during annealing.
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http://dx.doi.org/10.1021/acs.inorgchem.0c01626DOI Listing
September 2020

Synthesis and Characterization of [(PbSe)][TiSe] Isomers.

Inorg Chem 2020 Aug 10;59(15):10928-10937. Epub 2020 Jul 10.

Department of Chemistry and Materials Science Institute, University of Oregon, Eugene, Oregon 97403, United States.

This work presents the preparation of a series of [(PbSe)][TiSe] isomers via a low temperature synthesis approach that exploits precursor nanoarchitecture to direct formation of specific isomers. The targeted isomers formed even when the precursors did not have the correct amount of each element to make a unit cell from each repeating sequence of elemental layers deposited. This suggests that the exact composition of the precursors is less important than the nanoarchitecture in directing the formation of the compounds. The as-deposited diffraction data show that the isomers begin to form during the deposition, and TiSe, in addition to PbSe and TiSe, are present in the specular diffraction patterns. HAADF-STEM images reveal impurity layers above and below an integer number of targeted isomer unit cells. The structural data suggest that TiSe forms as Se is deposited on the initial Ti layers and remains throughout isomer self-assembly. During growth, the isomers deplete the local supply of Ti and Pb, creating diffusion gradients that drive additional cations toward the growth front, which leaves surface impurity layers of TiSe and TiO after the supply of Pb is exhausted. The deposited stacking sequences direct formation of the targeted isomers, but fewer repeating units form than intended due to the lack of material per layer in the precursor and formation of impurity layers. All isomers have negative Hall and Seebeck coefficients, indicating that electrons are the majority carrier. The carrier concentration and conductivity of the isomers increase with the number of interfaces in the unit cell, resulting from charge donation between adjacent layers. The opposite variation of the carrier concentration and mobility with temperature result in minima in the resistivity between 50 and 100 K. The very weak temperature dependence of the carrier concentration likely results from changes in the amount of charge transfer between the layers with temperature.
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http://dx.doi.org/10.1021/acs.inorgchem.0c01416DOI Listing
August 2020

Controlling the Self-Assembly of New Metastable Tin Vanadium Selenides Using Composition and Nanoarchitecture of Precursors.

J Am Chem Soc 2020 Jul 14;142(30):13145-13154. Epub 2020 Jul 14.

Department of Chemistry and Materials Science Institute, University of Oregon, Eugene, Oregon 97403, United States.

In solid-state chemistry, the direct reaction of elements at low temperatures is limited by low solid-state interdiffusion rates. This and the limited number of processing parameters often prevent the synthesis of metastable compounds. Precisely controlling the number of atoms and nanoarchitecture of layered elemental precursors enabled the selective synthesis of two closely related metastable tin vanadium selenides via near-diffusionless reactions at low temperatures. Although the nanoarchitectures of the precursors required to form [(SnSe)](VSe) and [(SnSe)](VSe) are very similar, controlling the local composition of the Sn|Se layers in the precursors enables the selective synthesis of either compound. The metastable alloy SnVSe was preferentially formed over [(SnSe)](VSe), which has the identical composition, by modifying the nanoarchitecture of the precursor. Ex situ in-plane X-ray diffraction and X-ray reflectivity collected as a function of annealing temperature provided information on lateral and perpendicular growth of [(SnSe)](VSe). The presence of Laue oscillations throughout the self-assembly provided atomic-scale information on the thickness of the [(SnSe)](VSe) domains, giving insights into the self-assembly process. A reaction mechanism is proposed and used to rationalize how composition and nanoarchitecture control the reaction pathway through the free energy landscape.
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http://dx.doi.org/10.1021/jacs.0c05505DOI Listing
July 2020

Synthesis of Metastable Inorganic Solids with Extended Structures.

Chemphyschem 2020 Jul 12;21(13):1345-1368. Epub 2020 Jun 12.

Department of Chemistry, University of Oregon, 1253 University of Oregon Eugene, Oregon, 97403, USA.

The number of known inorganic compounds is dramatically less than predicted due to synthetic challenges, which often constrains products to only the thermodynamically most stable compounds. Consequently, a mechanism-based approach to inorganic solids with designed structures is the holy grail of solid state synthesis. This article discusses a number of synthetic approaches using the concept of an energy landscape, which describes the complex relationship between the energy of different atomic configurations as a function of a variety of parameters such as initial structure, temperature, pressure, and composition. Nucleation limited synthesis approaches with high diffusion rates are contrasted with diffusion limited synthesis approaches. One challenge to the synthesis of new compounds is the inability to accurately predict what structures might be local free energy minima in the free energy landscape. Approaches to this challenge include predicting potentially stable compounds thorough the use of structural homologies and/or theoretical calculations. A second challenge to the synthesis of metastable inorganic solids is developing approaches to move across the energy landscape to a desired local free energy minimum while avoiding deeper free energy minima, such as stable binary compounds, as reaction intermediates. An approach using amorphous intermediates is presented, where local composition can be used to prepare metastable compounds. Designed nanoarchitecture built into a precursor can be preserved at low reaction temperatures and used to direct the reaction to specific structural homologs.
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http://dx.doi.org/10.1002/cphc.202000199DOI Listing
July 2020

The association between N-methylnaltrexone, a peripherally acting mu-opioid receptor antagonist, and clinical outcomes in patients undergoing robotic-assisted radical cystectomy.

World J Urol 2020 Dec 18;38(12):3113-3119. Epub 2020 Feb 18.

Department of Urology, David Geffen School of Medicine At UCLA, 300 Stein Plaza, Suite 348, Los Angeles, CA, 90095, USA.

Purpose: To assess the impact of N-methylnaltrexone, a peripherally acting mu-opioid receptor antagonist, on the post-operative recovery of patients undergoing robotic-assisted radical cystectomy for bladder cancer.

Methods: We retrospectively reviewed patients undergoing robotic-assisted radical cystectomy by a single surgeon (KC) prior to (control group) and after (treatment group) the routine use of N-methylnaltrexone. Kaplan-Meier curves and the log-rank test were used to quantify time to flatus, bowel movement, and discharge. Daily mean opioid use, daily pain assessment rating, and episodes of severe pain (7-10/10) were compared. Gastrointestinal-related complications, including ileus, emesis, and/or need for post-op nasogastric tube placement, and 30-day readmissions were also compared between groups. Charge capture data were compared between groups to analyze cost impact.

Results: 29 patients each in the control and treatment group met inclusion criteria. Patients receiving N-methylnaltrexone had reduced length of stay compared with no N-methylnaltrexone (median 4 vs. 7 days, p < 0.01). Time to flatus and bowel movement, however, were similar. In a multivariable analysis controlling for possible confounders, however, the improvement in length of stay associated with N-methylnaltrexone use did not reach statistical significance (p = 0.11). Episodes of severe pain and composite gastrointestinal-related complications were reduced in the N-methylnaltrexone group (44.8% vs. 10.3%, p < 0.01). The reduction in length of stay was associated with approximately $10,500 in cost savings per patient.

Conclusions: In this study, N-methylnaltrexone was associated with reduced length of stay, fewer episodes of severe pain, and reduced costs. These results provide the impetus for further study.
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http://dx.doi.org/10.1007/s00345-020-03117-yDOI Listing
December 2020

The association between N-methylnaltrexone, a peripherally acting mu-opioid receptor antagonist, and clinical outcomes in patients undergoing robotic-assisted radical cystectomy.

World J Urol 2020 Dec 18;38(12):3113-3119. Epub 2020 Feb 18.

Department of Urology, David Geffen School of Medicine At UCLA, 300 Stein Plaza, Suite 348, Los Angeles, CA, 90095, USA.

Purpose: To assess the impact of N-methylnaltrexone, a peripherally acting mu-opioid receptor antagonist, on the post-operative recovery of patients undergoing robotic-assisted radical cystectomy for bladder cancer.

Methods: We retrospectively reviewed patients undergoing robotic-assisted radical cystectomy by a single surgeon (KC) prior to (control group) and after (treatment group) the routine use of N-methylnaltrexone. Kaplan-Meier curves and the log-rank test were used to quantify time to flatus, bowel movement, and discharge. Daily mean opioid use, daily pain assessment rating, and episodes of severe pain (7-10/10) were compared. Gastrointestinal-related complications, including ileus, emesis, and/or need for post-op nasogastric tube placement, and 30-day readmissions were also compared between groups. Charge capture data were compared between groups to analyze cost impact.

Results: 29 patients each in the control and treatment group met inclusion criteria. Patients receiving N-methylnaltrexone had reduced length of stay compared with no N-methylnaltrexone (median 4 vs. 7 days, p < 0.01). Time to flatus and bowel movement, however, were similar. In a multivariable analysis controlling for possible confounders, however, the improvement in length of stay associated with N-methylnaltrexone use did not reach statistical significance (p = 0.11). Episodes of severe pain and composite gastrointestinal-related complications were reduced in the N-methylnaltrexone group (44.8% vs. 10.3%, p < 0.01). The reduction in length of stay was associated with approximately $10,500 in cost savings per patient.

Conclusions: In this study, N-methylnaltrexone was associated with reduced length of stay, fewer episodes of severe pain, and reduced costs. These results provide the impetus for further study.
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http://dx.doi.org/10.1007/s00345-020-03117-yDOI Listing
December 2020

Using spatial tracking with magnetic resonance imaging/ultrasound-guided biopsy to identify unilateral prostate cancer.

BJU Int 2020 03 25;125(3):399-406. Epub 2019 Nov 25.

Department of Urology, University of California, Los Angeles, CA, USA.

Objectives: To create reliable predictive metrics of unilateral disease using spatial tracking from a fusion device, thereby improving patient selection for hemi-gland ablation of prostate cancer.

Patients And Methods: We identified patients who received magnetic resonance imaging (MRI)/ultrasound-guided biopsy and radical prostatectomy at a single institution between 2011 and 2018. In addition to standard clinical features, we extracted quantitative features related to biopsy core and MRI target locations predictive of tumour unilaterality. Classification and Regression Tree (CART) analysis was used to create a decision tree (DT) for identifying cancer laterality. We evaluated concordance of model-determined laterality with final surgical pathology.

Results: A total of 173 patients were identified with biopsy coordinates and surgical pathology available. Based on CART analysis, in addition to biopsy- and MRI-confirmed disease unilaterality, patients should be further screened for cancer detected within 7 mm of midline in a 40 mL prostate, which equates to the central third of any-sized prostate by radius. The area under the curve for this DT was 0.82. Standard diagnostics and the DT correctly identified disease laterality in 73% and 80% of patients, respectively (P = 0.13). Of the patients identified as unilateral by standard diagnostics, 47% had undetected contralateral disease or were otherwise incorrectly identified. This error rate was reduced to 17% (P = 0.01) with the DT.

Conclusion: Using spatial tracking from fusion devices, a DT was more reliable for identifying laterality of prostate cancer compared to standard diagnostics. Patients with cancer detected within the central third of the prostate by radius are poor hemi-gland ablation candidates due to the risk of midline extension of tumour.
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http://dx.doi.org/10.1111/bju.14943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444382PMC
March 2020

Crystallography at the nanoscale: planar defects in ZnO nanospikes.

J Appl Crystallogr 2019 Oct 29;52(Pt 5):1009-1015. Epub 2019 Aug 29.

Synthesis and Real Structure and Institute for Material Science, Kiel University, Kaiserstrasse 2, Kiel 24143, Germany.

The examination of anisotropic nanostructures, such as wires, platelets or spikes, inside a transmission electron microscope is normally performed only in plan view. However, intrinsic defects such as growth twin interfaces could occasionally be concealed from direct observation for geometric reasons, leading to superposition. This article presents the shadow-focused ion-beam technique to prepare multiple electron-beam-transparent cross-section specimens of ZnO nanospikes, via a procedure which could be readily extended to other anisotropic structures. In contrast with plan-view data of the same nanospikes, here the viewing direction allows the examination of defects without superposition. By this method, the coexistence of two twin configurations inside the wurtzite-type structure is observed, namely and , which were not identified during the plan-view observations owing to superposition of the domains. The defect arrangement could be the result of coalescence twinning of crystalline nuclei formed on the partially molten Zn substrate during the flame-transport synthesis. Three-dimensional defect models of the twin interface structures have been derived and are correlated with the plan-view investigations by simulation.
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http://dx.doi.org/10.1107/S1600576719009415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6782080PMC
October 2019

Positive surgical margins at radical prostatectomy in the United States: Institutional variations and predictive factors.

Urol Oncol 2020 01 16;38(1):1.e17-1.e23. Epub 2019 Sep 16.

Institute of Urologic Oncology (IUO) at UCLA, Department a of Urology, David Geffen School of Medicine, Los Angeles, CA.

Introduction: Positive surgical margins (PSMs) are associated with treatment failure after radical prostatectomy (RP) for patients with prostate cancer (CaP). We investigated institutional variations in PSM after RP, as well as clinical and demographic factors predicting PSM.

Patients And Methods: Patients undergoing RP for clinically localized CaP were identified in the National Cancer Database in 2010 to 2013 and clinicodemographics were recorded. Treating institution was defined as academic (AMC) or nonacademic medical centers (nAMC). The primary outcome was the PSM rate. Multivariable logistic regression and propensity matching with inverse probability treatment weighing were used to both compare outcomes between AMC and nAMC and to identify predictors of PSM following RP.

Results: A total of 167,260 patients met our inclusion criteria. PSM rate was significantly lower in patients treated at AMC (13,435, 18.9%) compared with 22,145 (23.0%) in those treated at nAMC (P < 0.01). The difference between PSM rate in AMC and nAMC was more pronounced in lower volume centers while it was not significant in higher volume centers. On multivariable analysis, age, race, prostate-specific antigen (PSA), biopsy Gleason score, comorbidity profile, insurance type, income, and treatment facility were significantly associated with PSM rate.

Conclusion: PSM rates appear to be lower at AMC and higher volume facilities, which can potentially reflect institutional differences in surgical quality. In addition, we identified several socioeconomic and demographic factors that contribute to the likelihood of PSM following RP for localized CaP, suggesting potential systematic variation in the quality of surgical care. The cause of this variation warrants further investigation and evaluation.
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http://dx.doi.org/10.1016/j.urolonc.2019.08.016DOI Listing
January 2020

Transcriptome-wide association study of multiple myeloma identifies candidate susceptibility genes.

Hum Genomics 2019 08 20;13(1):37. Epub 2019 Aug 20.

Division of Genetics and Epidemiology, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK.

Background: While genome-wide association studies (GWAS) of multiple myeloma (MM) have identified variants at 23 regions influencing risk, the genes underlying these associations are largely unknown. To identify candidate causal genes at these regions and search for novel risk regions, we performed a multi-tissue transcriptome-wide association study (TWAS).

Results: GWAS data on 7319 MM cases and 234,385 controls was integrated with Genotype-Tissue Expression Project (GTEx) data assayed in 48 tissues (sample sizes, N = 80-491), including lymphocyte cell lines and whole blood, to predict gene expression. We identified 108 genes at 13 independent regions associated with MM risk, all of which were in 1 Mb of known MM GWAS risk variants. Of these, 94 genes, located in eight regions, had not previously been considered as a candidate gene for that locus.

Conclusions: Our findings highlight the value of leveraging expression data from multiple tissues to identify candidate genes responsible for GWAS associations which provide insight into MM tumorigenesis. Among the genes identified, a number have plausible roles in MM biology, notably APOBEC3C, APOBEC3H, APOBEC3D, APOBEC3F, APOBEC3G, or have been previously implicated in other malignancies. The genes identified in this TWAS can be explored for follow-up and validation to further understand their role in MM biology.
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http://dx.doi.org/10.1186/s40246-019-0231-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700979PMC
August 2019

Predictors of Patient-Reported Outcomes at 2 Years After Revision Anterior Cruciate Ligament Reconstruction.

Am J Sports Med 2019 08 18;47(10):2394-2401. Epub 2019 Jul 18.

All authors are listed in the Authors section at the end of this article.

Background: Patient-reported outcomes (PROs) are a valid measure of results after revision anterior cruciate ligament (ACL) reconstruction. Revision ACL reconstruction has been documented to have worse outcomes when compared with primary ACL reconstruction. Understanding positive and negative predictors of PROs will allow surgeons to modify and potentially improve outcome for patients.

Purpose/hypothesis: The purpose was to describe PROs after revision ACL reconstruction and test the hypothesis that patient- and technique-specific variables are associated with these outcomes.

Study Design: Cohort study; Level of evidence, 2.

Methods: Patients undergoing revision ACL reconstruction were identified and prospectively enrolled by 83 surgeons over 52 sites. Data included baseline demographics, surgical technique and pathology, and a series of validated PRO instruments: International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index, and Marx Activity Rating Scale. Patients were followed up at 2 years and asked to complete the identical set of outcome instruments. Multivariate regression models were used to control for a variety of demographic and surgical factors to determine the positive and negative predictors of PRO scores at 2 years after revision surgery.

Results: A total of 1205 patients met the inclusion criteria and were successfully enrolled: 697 (58%) were male, with a median cohort age of 26 years. The median time since their most recent previous ACL reconstruction was 3.4 years. Two-year questionnaire follow-up was obtained from 989 patients (82%). The most significant positive predictors of 2-year IKDC scores were a high baseline IKDC score, high baseline Marx activity level, male sex, and having a longer time since the most recent previous ACL reconstruction, while negative predictors included having a lateral meniscectomy before the revision ACL reconstruction or having grade 3/4 chondrosis in either the trochlear groove or the medial tibial plateau at the time of the revision surgery. For KOOS, having a high baseline score and having a longer time between the most recent previous ACL reconstruction and revision surgery were significant positive predictors for having a better (ie, higher) 2-year KOOS, while having a lateral meniscectomy before the revision ACL reconstruction was a consistent predictor for having a significantly worse (ie, lower) 2-year KOOS. Statistically significant positive predictors for 2-year Marx activity levels included higher baseline Marx activity levels, younger age, male sex, and being a nonsmoker. Negative 2-year activity level predictors included having an allograft or a biologic enhancement at the time of revision surgery.

Conclusion: PROs after revision ACL reconstruction are associated with a variety of patient- and surgeon-related variables. Understanding positive and negative predictors of PROs will allow surgeons to guide patient expectations as well as potentially improve outcomes.
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http://dx.doi.org/10.1177/0363546519862279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335592PMC
August 2019

Predicting Short-term Outcomes After Radical Cystectomy Based on Frailty.

Urology 2019 11 12;133:25-33. Epub 2019 Jul 12.

Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA; UCLA Fielding School of Public Health, Los Angeles, CA; UCLA School of Nursing, Los Angeles, CA.

Objective: To evaluate the impact of frailty on adverse perioperative outcomes in patients treated with radical cystectomy for bladder cancer.

Material And Methods: We identified 9459 adults (age ≥18) in the Nationwide Readmission Database who underwent radical cystectomy in 2014 for bladder cancer. We defined patients' frailty status using Johns Hopkins Adjusted Clinical Groups frailty-defining diagnosis indicator and compared in-hospital mortality, ICU-level complications, 30-day readmissions, nonhome discharge, length of hospitalization, and hospital-related costs between frail and nonfrail patients using χ tests. We used multivariate logistic regression to identify predictors of the primary outcomes of interest.

Results: Of 9459 patients undergoing radical cystectomy, 7.1% (n = 673) met criteria. Frail patients were more likely than nonfrail patients to have comorbid conditions (68.2% vs 59.7%; P= .005), in-hospital mortality (4.2% vs 1.5%; P= .04), ICU-level complications (52.9% vs 18.6%; P<.001), nonhome discharge (33.9% vs 11.6%; P <.001), longer length of stay (median 15 vs 7 days; P<.001), and higher median cost of the index admission ($39,665 vs $27,307). Frailty was the strongest independent predictor of ICU-level complications, nonhome discharge, increased length of stay, and hospital-related costs of any covariate.

Conclusion: Frail patients receiving radical cystectomy were more likely than nonfrail patients to have adverse perioperative outcomes and higher odds of in-hospital mortality, ICU-level complications, nonhome discharge, increased length of stay, and hospital-related costs. Preoperative consideration of frailty may be useful in clinical guidance and shared decision-making.
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http://dx.doi.org/10.1016/j.urology.2019.04.057DOI Listing
November 2019

Relationship Between Sports Participation After Revision Anterior Cruciate Ligament Reconstruction and 2-Year Patient-Reported Outcome Measures.

Am J Sports Med 2019 07 21;47(9):2056-2066. Epub 2019 Jun 21.

Investigation performed at Slocum Research and Education Foundation, Eugene, Oregon, USA.

Background: Anterior cruciate ligament (ACL) revision cohorts continually report lower outcome scores on validated knee questionnaires than primary ACL cohorts at similar time points after surgery. It is unclear how these outcomes are associated with physical activity after physician clearance for return to recreational or competitive sports after ACL revision surgery.

Hypotheses: Participants who return to either multiple sports or a singular sport after revision ACL surgery will report decreased knee symptoms, increased activity level, and improved knee function as measured by validated patient-reported outcome measures (PROMs) and compared with no sports participation. Multisport participation as compared with singular sport participation will result in similar increased PROMs and activity level.

Study Design: Cross-sectional study; Level of evidence, 3.

Methods: A total of 1205 patients who underwent revision ACL reconstruction were enrolled by 83 surgeons at 52 clinical sites. At the time of revision, baseline data collected included the following: demographics, surgical characteristics, previous knee treatment and PROMs, the International Knee Documentation Committee (IKDC) questionnaire, Marx activity score, Knee injury and Osteoarthritis Outcome Score (KOOS), and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). A series of multivariate regression models were used to evaluate the association of IKDC, KOOS, WOMAC, and Marx Activity Rating Scale scores at 2 years after revision surgery by sports participation category, controlling for known significant covariates.

Results: Two-year follow-up was obtained on 82% (986 of 1205) of the original cohort. Patients who reported not participating in sports after revision surgery had lower median PROMs both at baseline and at 2 years as compared with patients who participated in either a single sport or multiple sports. Significant differences were found in the change of scores among groups on the IKDC ( < .0001), KOOS-Symptoms ( = .01), KOOS-Sports and Recreation ( = .04), and KOOS-Quality of Life ( < .0001). Patients with no sports participation were 2.0 to 5.7 times more likely than multiple-sport participants to report significantly lower PROMs, depending on the specific outcome measure assessed, and 1.8 to 3.8 times more likely than single-sport participants (except for WOMAC-Stiffness, = .18), after controlling for known covariates.

Conclusion: Participation in either a single sport or multiple sports in the 2 years after ACL revision surgery was found to be significantly associated with higher PROMs across multiple validated self-reported assessment tools. During follow-up appointments, surgeons should continue to expect that patients who report returning to physical activity after surgery will self-report better functional outcomes, regardless of baseline activity levels.
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http://dx.doi.org/10.1177/0363546519856348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6939628PMC
July 2019

Focal Therapy Should Not Be Considered for Men with Gleason Grade Group 3-5 Prostate Cancer.

Eur Urol Focus 2020 03 13;6(2):203-204. Epub 2019 Jun 13.

Department of Urology, University of California Los Angeles, Los Angeles, CA, USA.

We argue that there is not enough evidence to safely offer focal therapy to men with Gleason grade group 3-5 prostate cancer.
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http://dx.doi.org/10.1016/j.euf.2019.06.005DOI Listing
March 2020

Do contemporary imaging and biopsy techniques reliably identify unilateral prostate cancer? Implications for hemiablation patient selection.

Cancer 2019 09 1;125(17):2955-2964. Epub 2019 May 1.

Department of Urology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California.

Background: Hemiablation is a less morbid treatment alternative for appropriately selected patients with unilateral prostate cancer (PCa). However, to the authors' knowledge, traditional diagnostic techniques inadequately identify appropriate candidates. In the current study, the authors quantified the accuracy for identifying hemiablation candidates using contemporary diagnostic techniques, including multiparametric magnetic resonance imaging (mpMRI) and MRI-fusion with complete systematic template biopsy.

Methods: A retrospective analysis of patients undergoing MRI and MRI-fusion prostate biopsy, including full systematic template biopsy, prior to radical prostatectomy in a single tertiary academic institution between June 2010 and February 2018 was performed. Hemiablation candidates had unilateral intermediate-risk PCa (Gleason score [GS] of 3+4 or 4+3, clinical T classification ≤T2, and prostate-specific antigen level <20 ng/dL) on MRI-fusion biopsy and 2) no contralateral highly or very highly suspicious Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) MRI lesions. Hemiablation candidates were inappropriately selected if pathologists identified contralateral GS ≥3+4 or high-risk ipsilateral PCa on prostatectomy. The authors tested a range of hemiablation inclusion criteria and performed multivariable analysis of preoperative predictors of undetected contralateral disease.

Results: Of 665 patients, 92 met primary hemiablation criteria. Of these 92 patients, 44 (48%) were incorrectly identified due to ipsilateral GS ≥3+4 tumors crossing the midline (21 patients), undetected distinct contralateral GS ≥3+4 tumors (20 patients), and/or ipsilateral high-risk PCa (3 patients) on prostatectomy. The rate of undetected contralateral disease ranged from 41% to 48% depending on inclusion criteria. On multivariable analysis, men with anterior index tumors were found to be 2.4 times more likely to harbor undetected contralateral GS ≥3+4 PCa compared with men with posterior lesions (P < .05).

Conclusions: Clinicians and patients must weigh the risk of inadequate oncologic treatment against the functional benefits of hemiablation. Further investigation into methods for improving patient selection for hemiablation is necessary.
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http://dx.doi.org/10.1002/cncr.32170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368458PMC
September 2019

Financial Margins for Prostate Cancer Surgery: Quantifying the Impact of Modifiable Cost Inputs in an Episode Based Reimbursement Model.

J Urol 2019 09 8;202(3):539-545. Epub 2019 Aug 8.

Department of Urology, David Geffen School of Medicine, UCLA, Los Angeles, California.

Purpose: The United States health care system is rapidly moving away from fee for service reimbursement in an effort to improve quality and contain costs. Episode based reimbursement is an increasingly relevant value based payment model of surgical care. We sought to quantify the impact of modifiable cost inputs on institutional financial margins in an episode based payment model for prostate cancer surgery.

Materials And Methods: A total of 157 consecutive patients underwent robotic radical prostatectomy in 2016 at a tertiary academic medical center. We compiled comprehensive episode costs and reimbursements from the most recent urology consultation for prostate cancer through 90 days postoperatively and benchmarked the episode price as a fixed reimbursement to the median reimbursement of the cohort. We identified 2 sources of modifiable costs with undefined empirical value, including preoperative prostate magnetic resonance imaging and perioperative functional recovery counseling visits, and then calculated the impact on financial margins (reimbursement minus cost) under an episode based payment.

Results: Although they comprised a small proportion of the total episode costs, varying the use of preoperative magnetic resonance imaging (33% vs 100% of cases) and functional recovery counseling visits (1 visit in 66% and 2 in 100%) reduced average expected episode financial margins up to 22.6% relative to the margin maximizing scenario in which no patient received these services.

Conclusions: Modifiable cost inputs have a substantial impact on potential operating margins for prostate cancer surgery under an episode based payment model. High cost health systems must develop the capability to analyze individual cost inputs and quantify the contribution to quality to inform value improvement efforts for multiple service lines.
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http://dx.doi.org/10.1097/JU.0000000000000283DOI Listing
September 2019

Cytoreductive nephrectomy in patients with metastatic renal cell carcinoma and venous thrombus-Trends and effect on overall survival.

Urol Oncol 2019 09 28;37(9):577.e9-577.e16. Epub 2019 Mar 28.

Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA. Electronic address:

Purpose: Patients with metastatic renal cell carcinoma (mRCC) commonly present with tumor thrombi in the renal vein and inferior vena cava (IVC). The benefit of cytoreductive nephrectomy (CN) in this population is unclear and the effect on overall survival (OS) has been incompletely evaluated.

Materials And Methods: We queried the National Cancer Database from 2010 to 2013 for patients diagnosed with mRCC and tumor thrombi, which was defined as renal vein, infradiaphragmatic IVC, or supradiaphragmatic IVC. Descriptive statistics were performed and associations between clinicopathologic variables and utilization of CN were analyzed. Patients were matched on the receipt of CN and Kaplan-Meier analyses and multivariable Cox proportional hazards models were used to estimate survival.

Results: In total, 8,629 patients were found to have mRCC during the study period. Approximately 27% (n = 2,376) had tumor thrombus. Tumor thrombus was associated with increased rates of CN utilization, however rates decreased as thrombus level increased. In a matched Kaplan-Meier analysis, CN was associated with improved OS in patients without thrombus, and with renal vein or infradiaphragmatic thrombus (all P < 0.01). Patients with supradiaphragmatic thrombus did not benefit from CN (P = 0.46). This effect was confirmed in a Cox proportional hazards model.

Conclusions: Tumor thrombus is common in patients with mRCC. OS is poor, and patient and tumor specific factors influence the use of CN. Despite discrepancies in utilization, CN is associated with improved OS, although this effect appears to be limited to those with mRCC and tumor thrombus limited to the renal vein and infradiaphragmatic IVC.
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http://dx.doi.org/10.1016/j.urolonc.2019.03.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698401PMC
September 2019
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