Publications by authors named "Mark Lee"

446 Publications

The prevalence of fracture extension in displaced femoral neck fractures in the elderly: A pilot study.

OTA Int 2019 Dec 14;2(4):e033. Epub 2019 May 14.

University of California Davis Medical Center, Sacramento, CA.

Objective: Arthroplasty is the common treatment for intracapsular femoral neck fractures in the elderly. Recent studies have shown that there may be more overall complications related to uncemented hemiarthroplasty compared to cemented, including more subsidence, intraoperative fractures, and postoperative fractures. Uncemented femoral components rely on a press fit, and the risk of these complications would be expected to increase in patients with unrecognized distal extension of femoral neck fractures. The purpose of this study is to determine the frequency of fracture extension of displaced femoral neck fractures in the elderly population.

Methods: The electronic medical record database at our institution was retrospectively reviewed to search for consecutive reports from 2005 to 2015 of patients 65 years or older that sustained an intracapsular femoral neck fracture who had computed tomography (CT) examinations of the injury. Exclusion criteria were CTs that were not fine cut (<1.5 mm cuts) or occult femoral neck fractures that were seen only on magnetic resonance imaging. This resulted in 60 patients that were included in the study. Within this subset of patients, the CT scans were reassessed to look for extension of the fracture beyond the boundaries of the femoral neck. Of particular interest, were fracture lines that extended distal to the femoral neck, since these have the potential to affect the fit of an uncemented femoral stem. Data on subject age, gender, body mass index (BMI), and bone mineral density (BMD) were also collected, and it was determined if these demographics were predictive in patients having fracture extension. Treatment and follow-up data were collected for the patients as well.

Results: Seven of 60 patients were identified to have fracture extension of intracapsular femoral neck fractures. The frequency of fracture extension of intracapsular femoral neck fractures distal to the femoral neck was 8.3% (5/60). All cases of fracture extension were nondisplaced or minimally displaced. 60% (3/5) of the distal fracture extensions were not diagnosed preoperatively by the radiologists or the treating orthopaedic surgeons. There was not a statistically significant difference when comparing age, gender, BMI, or BMD of the population group with distal fracture extension to that of the rest of the patient cohort.

Conclusions: To our knowledge, this is the first study to report the frequency of fracture extension of displaced femoral neck fractures in the elderly population. The 8.3% rate of distal fracture extension in elderly femoral neck fractures may help explain the higher rate of subsidence, postoperative fracture and intraoperative fracture when applying uncemented hemiarthroplasty compared to cemented arthroplasty. It is important to be aware of the potential for this phenomenon.
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http://dx.doi.org/10.1097/OI9.0000000000000033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997120PMC
December 2019

The Use of Quetiapine for the Management of Nausea and Vomiting in Idiopathic Parkinson's Disease.

J Palliat Care 2021 Apr 28:8258597211013952. Epub 2021 Apr 28.

Palliative Medicine, 102597St Benedict's Hospice and Specialist Palliative Care Centre, Sunderland, United Kingdom.

Nausea and vomiting are common in the palliative demographic and can significantly affect quality of life. Initial management strategies involve tailoring antiemetic selection to the underlying cause. Whilst in refractory cases, management is often switched to a broader spectrum antipsychotic agent (such as levomepromazine or olanzapine). Yet in individuals with idiopathic Parkinson's disease antiemetics which antagonize central dopamine are avoided, as they have the potential to exacerbate motor control or even precipitate Parkinsonism-hyperpyrexia syndrome. Consequently, antiemetic options for patients with idiopathic Parkinson's disease are limited. This is the first report of quetiapine being successfully used for the management of nausea and vomiting in an individual with idiopathic Parkinson's disease.
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http://dx.doi.org/10.1177/08258597211013952DOI Listing
April 2021

The Use of Quetiapine for the Management of Nausea and Vomiting in Idiopathic Parkinson's Disease.

J Palliat Care 2021 Apr 28:8258597211013952. Epub 2021 Apr 28.

Palliative Medicine, 102597St Benedict's Hospice and Specialist Palliative Care Centre, Sunderland, United Kingdom.

Nausea and vomiting are common in the palliative demographic and can significantly affect quality of life. Initial management strategies involve tailoring antiemetic selection to the underlying cause. Whilst in refractory cases, management is often switched to a broader spectrum antipsychotic agent (such as levomepromazine or olanzapine). Yet in individuals with idiopathic Parkinson's disease antiemetics which antagonize central dopamine are avoided, as they have the potential to exacerbate motor control or even precipitate Parkinsonism-hyperpyrexia syndrome. Consequently, antiemetic options for patients with idiopathic Parkinson's disease are limited. This is the first report of quetiapine being successfully used for the management of nausea and vomiting in an individual with idiopathic Parkinson's disease.
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http://dx.doi.org/10.1177/08258597211013952DOI Listing
April 2021

Patterns of Recurrence of Phonotraumatic Vocal Fold Lesions Suggest Distinct Mechanisms of Injury.

Laryngoscope 2021 Apr 9. Epub 2021 Apr 9.

The Sean Parker Institute for the Voice, Department of Otolaryngology-Head & Neck Surgery, Weill Cornell Medicine, New York, New York, USA.

Objectives/hypothesis: To examine patterns of recurrence of benign phonotraumatic vocal fold lesions over time for insights into pathophysiology.

Study Design: Case series with mathematical modeling.

Methods: Medical records and stroboscopic exams of adults who underwent microlaryngoscopic resection of phonotraumatic vocal fold lesions over a 13-year period were reviewed for time to recurrence after surgery. Uniform and log-normal probability distributions were fitted to the time to recurrence curves for vocal fold polyps, midfold masses, and pseudocysts. Model fits were compared using the Akaike information criterion corrected, a standard measure of the goodness of fit. Stochastic simulations were used to verify that the mechanistic hypotheses were concordant with the selected probability distributions and empiric data.

Results: Of 567 patients who underwent microlaryngoscopic resection, 65 had a recurrence (16 polyps, 14 midfold masses, and 35 pseudocysts). Midfold mass and pseudocyst recurrences were predominantly seen in younger women. Polyps were best fit by a uniform distribution rather than log-normal, whereas midfold masses and pseudocysts were better fit by log-normal rather than uniform. Stochastic simulations suggest that polyps recur sporadically according to a paroxysmal-developmental model, whereas midfold mass and pseudocyst recurrences follow a force-multiplication, damage-accumulation process.

Conclusions: Vocal fold polyps are acute lesions evenly distributed by age and gender that recur uniformly over time, suggesting they arise from sudden tissue reactions to phonotraumatic stress. Pseudocysts and midfold fibrous masses are chronic lesions predominantly found in young women that recur with log-normal distribution over time, suggesting gradual damage accumulation in larynges predisposed to enhanced phonotrauma.

Level Of Evidence: 4 Laryngoscope, 2021.
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http://dx.doi.org/10.1002/lary.29531DOI Listing
April 2021

Comprehensive Intraprocedural Unfractionated Heparin Protocol During Catheter Ablation of Atrial Fibrillation in the Presence of Direct Oral Anticoagulants and Wide Spectrum of Body Mass Index.

J Cardiovasc Pharmacol Ther 2021 Mar 22:1074248421998492. Epub 2021 Mar 22.

323637MemorialCare Heart & Vascular Institute, Long Beach, CA, USA.

Introduction: Data on optimal dosing of unfractionated heparin (UFH) in the presence of a direct oral anticoagulant (DOAC) to achieve and maintain an activated clotting time (ACT) of ≥300 seconds during catheter ablation of atrial fibrillation (CA-AF) are limited and prevalence of obesity adds to the unpredictable response to UFH.

Methods And Results: One hundred seventeen consecutive patients undergoing CA-AF were prospectively administered weight-adjusted, weight-based UFH using a pre-specified detailed protocol and retrospectively analyzed. Due to lack of distribution of UFH into muscle or adipose tissue and lower degree of vascularity in the latter compartment, each patient's ideal and actual weights were used to determine the adjusted-weight for use in all UFH doses. A UFH bolus of 200 units/kg was administered intravenously followed by an infusion of 35 units/kg/hour. The mean age was 65 years, and 85 patients (72.6%) were male. The average body mass index (BMI) was 30 (range 18-50) kg/m. After the initial UFH bolus dose, 99 patients (84.6%) achieved ACT ≥300 sec with a mean (± SD) of 380 ± 79 sec. The mean time to reach an ACT ≥300 in all patients was 14.6 ± 12.4 minutes. Among all measured ACT values, 423 (90.8%) were ≥300 seconds. These results were consistent within all BMI categories. There were no intraprocedural thrombotic or hemorrhagic complications. Two patients (1.7%) sustained groin vascular access site hematoma without subsequent intervention and 7 patients (6%) experienced minor oozing post-procedurally.

Conclusions: Our comprehensive weight-adjusted, weight-based UFH protocol, during CA-AF in presence of a DOAC, rapidly achieved and maintained an effective ACT irrespective of BMI.
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http://dx.doi.org/10.1177/1074248421998492DOI Listing
March 2021

Assessment of Screening Mammography Recommendations by Breast Cancer Centers in the US.

JAMA Intern Med 2021 May;181(5):717-719

Divisions of Breast and Endocrine Surgery, Department of Surgery, Weill Cornell Medicine, New York, New York.

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http://dx.doi.org/10.1001/jamainternmed.2021.0157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961465PMC
May 2021

Response Rates to Anti-PD-1 Immunotherapy in Microsatellite-Stable Solid Tumors With 10 or More Mutations per Megabase.

JAMA Oncol 2021 Feb 18. Epub 2021 Feb 18.

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.

Importance: In June 2020, the US Food and Drug Administration approved the anti-programmed cell death 1 drug pembrolizumab for patients with malignant solid tumors of any histologic type with high tumor mutational burden (TMB; ≥10 mutations per megabase). The predictive value of this universal cutoff for high TMB is not well understood.

Objective: To examine the performance of a universal definition of high TMB in an independent cohort of patients with solid tumors treated with immune checkpoint inhibitors.

Design, Setting, And Participants: This retrospective cohort study included 1678 patients at a single cancer referral center treated with immune checkpoint inhibitors from January 1, 2015, to December 31, 2018. Patients had 16 different cancer types and were treated with anti-programmed cell death 1 or programmed cell death ligand-1 immunotherapy. Tumors underwent next-generation sequencing.

Exposures: At least 1 dose of immune checkpoint inhibitors.

Main Outcomes And Measures: Best overall response to immune checkpoint inhibitor therapy. The hypothesis tested was formulated after data collection and prior to analysis.

Results: Of 1678 patients, 924 (55%) were male, and the median age was 64 years (interquartile range, 55-71 years). Using the universal cutoff of 10 mutations per megabase, 416 tumors (25%) were categorized as having high TMB. Across cancer types, the proportion of TMB-high tumors ranged from 0% of kidney cancers to 53% of melanomas (113 of 214). Tumors categorized as TMB-high had higher response rates compared with TMB-low tumors in only 11 of 16 cancer types. In the entire cohort, response rates increased with higher cutoffs for TMB-high categorization, reaching 41% (169 of 416) for TMB more than 10 and 56% (90 of 161) for TMB more than 18, the highest TMB decile. Response rates also increased with TMB percentile within cancer type. Using cancer-specific cutoffs, 457 tumors (27%) were categorized as TMB-high. Response rates within cancer type ranged from 4% for pancreatic cancer (1 of 26) to 70% for melanoma (46 of 66). Cancer-specific cutoffs were associated with numerically higher response rates for TMB-high compared with TMB-low tumors in 14 of 16 cancer types.

Conclusions And Relevance: The data from this cohort study validate the finding of generally higher response rates following immune checkpoint inhibitor therapy for tumors with TMB of 10 or more mutations per megabase, across multiple cancer types. However, the predictive value of a universal numerical threshold for TMB-high was limited, owing to variability across cancer types and unclear associations with survival outcomes. Further investigation will help define cancer type-specific TMB cutoffs to guide decision-making.
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http://dx.doi.org/10.1001/jamaoncol.2020.7684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893543PMC
February 2021

Disciplinary practices among orphaned children in Sub-Saharan Africa.

PLoS One 2021 4;16(2):e0246578. Epub 2021 Feb 4.

Department of Sociology, University of Minnesota, Minneapolis, MN, United States of America.

Objectives: This study considers whether orphans' experiences with physically and psychologically violent discipline differ from non-orphans in sub-Saharan Africa, and to what extent national, community, household, caretaker, and child characteristics explain those differences.

Methods: We use cross-sectional Multiple Indicator Cluster Surveys (MICS) administered between 2010-2017 in 14 sub-Saharan African countries. The sample included 125,197 children, of which 2,937 were maternal orphans, 9,113 were paternal orphans, and 1,858 were double orphans. We estimate the difference between orphans and non-orphans experience of harsh discipline using multivariable logistic regressions with country fixed effects and clustered standard errors.

Results: Findings show that orphaned children experience less harsh discipline in the home. With the exception of double orphans' experience with physically violent discipline, these differences persisted even after controlling for a rich set of child, household, and caretaker characteristics.

Conclusions: We propose two alternative explanations for our surprising findings and provide a supplementary analysis to help arbitrate between them. The evidence suggests that orphaned children (especially those with a deceased mother) are less likely to experience harsh discipline because of lower caretaker investment in their upbringing. We encourage future research to draw on in-depth interviews or household surveys with discipline data from multiple children in a home to further unpack why orphans tend to experience less harsh punishment than other children.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246578PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861390PMC
February 2021

The Species-Specific Acquisition and Diversification of a K1-like Family of Killer Toxins in Budding Yeasts of the Saccharomycotina.

PLoS Genet 2021 Feb 4;17(2):e1009341. Epub 2021 Feb 4.

Department of Biological Sciences, University of Idaho, Moscow, Idaho, United States of America.

Killer toxins are extracellular antifungal proteins that are produced by a wide variety of fungi, including Saccharomyces yeasts. Although many Saccharomyces killer toxins have been previously identified, their evolutionary origins remain uncertain given that many of these genes have been mobilized by double-stranded RNA (dsRNA) viruses. A survey of yeasts from the Saccharomyces genus has identified a novel killer toxin with a unique spectrum of activity produced by Saccharomyces paradoxus. The expression of this killer toxin is associated with the presence of a dsRNA totivirus and a satellite dsRNA. Genetic sequencing of the satellite dsRNA confirmed that it encodes a killer toxin with homology to the canonical ionophoric K1 toxin from Saccharomyces cerevisiae and has been named K1-like (K1L). Genomic homologs of K1L were identified in six non-Saccharomyces yeast species of the Saccharomycotina subphylum, predominantly in subtelomeric regions of the genome. When ectopically expressed in S. cerevisiae from cloned cDNAs, both K1L and its homologs can inhibit the growth of competing yeast species, confirming the discovery of a family of biologically active K1-like killer toxins. The sporadic distribution of these genes supports their acquisition by horizontal gene transfer followed by diversification. The phylogenetic relationship between K1L and its genomic homologs suggests a common ancestry and gene flow via dsRNAs and DNAs across taxonomic divisions. This appears to enable the acquisition of a diverse arsenal of killer toxins by different yeast species for potential use in niche competition.
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http://dx.doi.org/10.1371/journal.pgen.1009341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888664PMC
February 2021

Pretreatment neutrophil-to-lymphocyte ratio and mutational burden as biomarkers of tumor response to immune checkpoint inhibitors.

Nat Commun 2021 02 1;12(1):729. Epub 2021 Feb 1.

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Treatment with immune checkpoint inhibitors (ICI) has demonstrated clinical benefit for a wide range of cancer types. Because only a subset of patients experience clinical benefit, there is a strong need for biomarkers that are easily accessible across diverse practice settings. Here, in a retrospective cohort study of 1714 patients with 16 different cancer types treated with ICI, we show that higher neutrophil-to-lymphocyte ratio (NLR) is significantly associated with poorer overall and progression-free survival, and lower rates of response and clinical benefit, after ICI therapy across multiple cancer types. Combining NLR with tumor mutational burden (TMB), the probability of benefit from ICI is significantly higher (OR = 3.22; 95% CI, 2.26-4.58; P < 0.001) in the NLR low/TMB high group compared to the NLR high/TMB low group. NLR is a suitable candidate for a cost-effective and widely accessible biomarker, and can be combined with TMB for additional predictive capacity.
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http://dx.doi.org/10.1038/s41467-021-20935-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851155PMC
February 2021

Antigen identification for HLA class I- and HLA class II-restricted T cell receptors using cytokine-capturing antigen-presenting cells.

Sci Immunol 2021 Jan;6(55)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.

A major limitation to understanding the associations of human leukocyte antigen (HLA) and CD8 and CD4 T cell receptor (TCR) genes with disease pathophysiology is the technological barrier of identifying which HLA molecules, epitopes, and TCRs form functional complexes. Here, we present a high-throughput epitope identification system that combines capture of T cell-secreted cytokines by barcoded antigen-presenting cells (APCs), cell sorting, and next-generation sequencing to identify class I- and class II-restricted epitopes starting from highly complex peptide-encoding oligonucleotide pools. We engineered APCs to express anti-cytokine antibodies, a library of DNA-encoded peptides, and multiple HLA class I or II molecules. We demonstrate that these engineered APCs link T cell activation-dependent cytokines with the DNA that encodes the presented peptide. We validated this technology by showing that we could select known targets of viral epitope-, neoepitope-, and autoimmune epitope-specific TCRs, starting from mixtures of peptide-encoding oligonucleotides. Then, starting from 10 TCRβ sequences that are found commonly in humans but lack known targets, we identified seven CD8 or CD4 TCR-targeted epitopes encoded by the human cytomegalovirus (CMV) genome. These included known epitopes, as well as a class I and a class II CMV epitope that have not been previously described. Thus, our cytokine capture-based assay makes use of a signal secreted by both CD8 and CD4 T cells and allows pooled screening of thousands of encoded peptides to enable epitope discovery for orphan TCRs. Our technology may enable identification of HLA-epitope-TCR complexes relevant to disease control, etiology, or treatment.
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http://dx.doi.org/10.1126/sciimmunol.abf4001DOI Listing
January 2021

The Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Molecular Diagnostic Testing.

Clin Infect Dis 2021 Jan 22. Epub 2021 Jan 22.

Division of Nephrology and Hypertension, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.

Background: Accurate molecular diagnostic tests are necessary for confirming a diagnosis of coronavirus disease 2019 (COVID-19). Direct detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acids in respiratory tract specimens informs patient, healthcare institution and public health level decision-making. The numbers of available SARS-CoV-2 nucleic acid detection tests are rapidly increasing, as is the COVID-19 diagnostic literature. Thus, the Infectious Diseases Society of America (IDSA) recognized a significant need for frequently updated systematic reviews of the literature to inform evidence-based best practice guidance.

Objective: The IDSA's goal was to develop an evidence-based diagnostic guideline to assist clinicians, clinical laboratorians, patients and policymakers in decisions related to the optimal use of SARS-CoV-2 nucleic acid amplification tests. In addition, we provide a conceptual framework for understanding molecular diagnostic test performance, discuss the nuance of test result interpretation in a variety of practice settings and highlight important unmet research needs in the COVID-19 diagnostic testing space.

Methods: IDSA convened a multidisciplinary panel of infectious diseases clinicians, clinical microbiologists, and experts in systematic literature review to identify and prioritize clinical questions and outcomes related to the use of SARS-CoV-2 molecular diagnostics. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations.

Results: The panel agreed on 17 diagnostic recommendations.

Conclusions: Universal access to accurate SARS-CoV-2 nucleic acid testing is critical for patient care, hospital infection prevention and the public response to the COVID-19 pandemic. Information on the clinical performance of available tests is rapidly emerging, but the quality of evidence of the current literature is considered moderate to very low. Recognizing these limitations, the IDSA panel weighed available diagnostic evidence and recommends nucleic acid testing for all symptomatic individuals suspected of having COVID-19. In addition, testing is recommended for asymptomatic individuals with known or suspected contact with a COVID-19 case. Testing asymptomatic individuals without known exposure is suggested when the results will impact isolation/quarantine/personal protective equipment (PPE) usage decisions, dictate eligibility for surgery, or inform solid organ or hematopoietic stem cell transplantation timing. Ultimately, prioritization of testing will depend on institutional-specific resources and the needs of different patient populations.
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http://dx.doi.org/10.1093/cid/ciab048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929045PMC
January 2021

Relationships between resource availability and elevation vary between metrics creating gradients of nutritional complexity.

Oecologia 2021 Jan 18;195(1):213-223. Epub 2021 Jan 18.

Comparative Plant and Fungal Biology, Royal Botanic Gardens Kew, Richmond, TW9 3AB, UK.

Plant and animal community composition changes at higher elevations on mountains. Plant and animal species richness generally declines with elevation, but the shape of the relationship differs between taxa. There are several proposed mechanisms, including the productivity hypotheses; that declines in available plant biomass confers fewer resources to consumers, thus supporting fewer species. We investigated resource availability as we ascended three aspects of Helvellyn mountain, UK, measuring several plant nutritive metrics, plant species richness and biomass. We observed a linear decline in plant species richness as we ascended the mountain but there was a unimodal relationship between plant biomass and elevation. Generally, the highest biomass values at mid-elevations were associated with the lowest nutritive values, except mineral contents which declined with elevation. Intra-specific and inter-specific increases in nutritive values nearer the top and bottom of the mountain indicated that physiological, phenological and compositional mechanisms may have played a role. The shape of the relationship between resource availability and elevation was different depending on the metric. Many consumers actively select or avoid plants based on their nutritive values and the abundances of consumer taxa vary in their relationships with elevation. Consideration of multiple nutritive metrics and of the nutritional requirements of the consumer may provide a greater understanding of changes to plant and animal communities at higher elevations. We propose a novel hypothesis for explaining elevational diversity gradients, which warrants further study; the 'nutritional complexity hypothesis', where consumer species coexist due to greater variation in the nutritional chemistry of plants.
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http://dx.doi.org/10.1007/s00442-020-04824-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882561PMC
January 2021

The association between tumor mutational burden and prognosis is dependent on treatment context.

Nat Genet 2021 01 4;53(1):11-15. Epub 2021 Jan 4.

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

In multiple cancer types, high tumor mutational burden (TMB) is associated with longer survival after treatment with immune checkpoint inhibitors (ICIs). The association of TMB with survival outside of the immunotherapy context is poorly understood. We analyzed 10,233 patients (80% non-ICI-treated, 20% ICI-treated) with 17 cancer types before/without ICI treatment or after ICI treatment. In non-ICI-treated patients, higher TMB (higher percentile within cancer type) was not associated with better prognosis; in fact, in many cancer types, higher TMB was associated with poorer survival, in contrast to ICI-treated patients in whom higher TMB was associated with longer survival.
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http://dx.doi.org/10.1038/s41588-020-00752-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796993PMC
January 2021

A Biomechanical Comparison of Trochanteric Versus Piriformis Reconstruction Nails for Femoral Neck Fracture Prophylaxis.

J Orthop Trauma 2020 Nov 27. Epub 2020 Nov 27.

Department of Orthopaedic Surgery, University of California Davis Medical Center, Sacramento, CA.

Objectives: To compare piriformis fossa to greater trochanteric entry cephalomedullary implants in an evaluation of femoral neck load to failure when the device is used for femoral shaft fractures with prophylaxis of an associated femoral neck fracture.

Methods: Thirty fourth-generation synthetic femur models were separated into 5 groups; intact femora, entry sites alone at the piriformis fossa or greater trochanter, and piriformis fossa and greater trochanteric entry sites after the insertion of a cephalomedullary nail. Each model was mechanically loaded with a flat plate against the superior femoral head along the mechanical axis and load to failure was recorded.

Results: Mean load to failure was 5487 ± 376 N in the intact femur, 3126 ± 387 N in the piriformis fossa entry site group, 3772 ± 558 N in the piriformis entry nail, 5332 ± 292 N for the greater trochanteric entry site, and 5406 ± 801 N for the greater trochanteric nail group. Both piriformis groups were significantly lower compared to the intact group. Both greater trochanteric groups were similar to the intact group and were statistically higher than the piriformis groups.

Conclusion: A piriformis fossa entry site with or without an intramedullary implant weakens the femoral neck in load to failure testing. A greater trochanteric entry yields a load to failure equivalent to that of an intact femoral neck. Instrumentation with a greater trochanteric cephalomedullary nail is significantly stronger than a piriformis fossa cephalomedullary nail during axial loading in a composite femur model.
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http://dx.doi.org/10.1097/BOT.0000000000002023DOI Listing
November 2020

Implementation of a Pooled Surveillance Testing Program for Asymptomatic SARS-CoV-2 Infections on a College Campus - Duke University, Durham, North Carolina, August 2-October 11, 2020.

MMWR Morb Mortal Wkly Rep 2020 Nov 20;69(46):1743-1747. Epub 2020 Nov 20.

On university campuses and in similar congregate environments, surveillance testing of asymptomatic persons is a critical strategy (1,2) for preventing transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). All students at Duke University, a private research university in Durham, North Carolina, signed the Duke Compact (3), agreeing to observe mandatory masking, social distancing, and participation in entry and surveillance testing. The university implemented a five-to-one pooled testing program for SARS-CoV-2 using a quantitative, in-house, laboratory-developed, real-time reverse transcription-polymerase chain reaction (RT-PCR) test (4,5). Pooling of specimens to enable large-scale testing while minimizing use of reagents was pioneered during the human immunodeficiency virus pandemic (6). A similar methodology was adapted for Duke University's asymptomatic testing program. The baseline SARS-CoV-2 testing plan was to distribute tests geospatially and temporally across on- and off-campus student populations. By September 20, 2020, asymptomatic testing was scaled up to testing targets, which include testing for residential undergraduates twice weekly, off-campus undergraduates one to two times per week, and graduate students approximately once weekly. In addition, in response to newly identified positive test results, testing was focused in locations or within cohorts where data suggested an increased risk for transmission. Scale-up over 4 weeks entailed redeploying staff members to prepare 15 campus testing sites for specimen collection, developing information management tools, and repurposing laboratory automation to establish an asymptomatic surveillance system. During August 2-October 11, 68,913 specimens from 10,265 graduate and undergraduate students were tested. Eighty-four specimens were positive for SARS-CoV-2, and 51% were among persons with no symptoms. Testing as a result of contact tracing identified 27.4% of infections. A combination of risk-reduction strategies and frequent surveillance testing likely contributed to a prolonged period of low transmission on campus. These findings highlight the importance of combined testing and contact tracing strategies beyond symptomatic testing, in association with other preventive measures. Pooled testing balances resource availability with supply-chain disruptions, high throughput with high sensitivity, and rapid turnaround with an acceptable workload.
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http://dx.doi.org/10.15585/mmwr.mm6946e1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676642PMC
November 2020

A biomimetic five-module chimeric antigen receptor (CAR) designed to target and eliminate antigen-specific T cells.

Proc Natl Acad Sci U S A 2020 11 2;117(46):28950-28959. Epub 2020 Nov 2.

Department of Immunobiology, The University of Arizona College of Medicine, Tucson, AZ 85724;

T cells express clonotypic T cell receptors (TCRs) that recognize peptide antigens in the context of class I or II MHC molecules (pMHCI/II). These receptor modules associate with three signaling modules (CD3γε, δε, and ζζ) and work in concert with a coreceptor module (either CD8 or CD4) to drive T cell activation in response to pMHCI/II. Here, we describe a first-generation biomimetic five-module chimeric antigen receptor (CAR). We show that 1) chimeric receptor modules built with the ectodomains of pMHCII assemble with CD3 signaling modules into complexes that redirect cytotoxic T lymphocyte (CTL) specificity and function in response to the clonotypic TCRs of pMHCII-specific CD4 T cells, and 2) surrogate coreceptor modules enhance the function of these complexes. Furthermore, we demonstrate that adoptively transferred CAR-CTLs can mitigate type I diabetes by targeting autoimmune CD4 T cells in NOD mice. This work provides a framework for the construction of biomimetic CARs that can be used as tools to study the impact of particular antigen-specific T cells in immune responses, and may hold potential for ameliorating diseases mediated by pathogenic T cells.
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http://dx.doi.org/10.1073/pnas.2012495117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682351PMC
November 2020

Novel 5-point 18-FDG-PET/CT visual scoring system for assessing treatment response in patients with oesophageal or gastro-oesophageal junction carcinoma.

J Med Imaging Radiat Oncol 2021 Feb 15;65(1):23-37. Epub 2020 Oct 15.

University of New South Wales, Sydney, New South Wales, Australia.

Introduction: The purpose of this study was to investigate the prognostic utility and reproducibility of a qualitative 5-point 18-fluorodeoxyglucose (FDG)-PET primary visual score (PVS) in patients with oesophageal and gastro-oesophageal junction (GOJ) cancer.

Methods: This was a retrospective review of patients with histologically proven oesophageal or GOJ cancer who received curative intent therapy. Clinical, pathological and imaging data were extracted from electronic medical records. Patients were required to have pre-treatment and post-treatment FDG-PET scans, that were evaluated with a 5-point primary visual score (prePVS, postPVS). The changes in PVS (ΔPVS) were correlated with progression-free survival and overall survival. Interobserver variability was assessed using Cohen's Kappa intraclass correlation and agreement.

Results: Sixty-seven patients were retrospectively identified. Two (3%), 36 (54%) and 29 (43%) of the patients had stage I, II and III disease respectively. Twenty-five (37%) patients had squamous cell carcinoma. Thirty-seven (55%) patients proceeded onto surgical resection. postPVS was associated with both PFS (P = 0.013) and OS (P = 0.0002). ΔPVS predicted for PFS (P = 0.002) and OS (P = 0.0003). When thresholds of response were considered, agreement was 80.6% (K = 0.78) and 74.6% (K = 0.69) for postPVS and ΔPVS respectively.

Conclusion: Qualitative assessment of oesophageal and GOJ cancers utilising FDG-PET is reproducible and may be able to prognosticate outcomes in patients undergoing treatment. Prospective validation is required.
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http://dx.doi.org/10.1111/1754-9485.13110DOI Listing
February 2021

Information sharing challenges in end-of-life care: a qualitative study of patient, family and professional perspectives on the potential of an Electronic Palliative Care Co-ordination System.

BMJ Open 2020 10 5;10(10):e037483. Epub 2020 Oct 5.

Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UK.

Objectives: To explore current challenges in interdisciplinary management of end-of-life care in the community and the potential of an Electronic Palliative Care Co-ordination System (EPaCCS) to facilitate the delivery of care that meets patient preferences.

Design: Qualitative study using interviews and focus groups.

Setting: Health and Social Care Services in the North of England.

Participants: 71 participants, 62 health and social care professionals, 9 patients and family members.

Results: Four key themes were identified: information sharing challenges; information sharing systems; perceived benefits of an EPaCCS and barriers to use and requirements for an EPaCCS. Challenges in sharing information were a source of frustration for health and social care professionals as well as patients, and were suggested to result in inappropriate hospital admissions. Current systems were perceived by participants to not work well-paper advance care planning (ACP) documentation was often unavailable or inaccessible, meaning it could not be used to inform decision-making at the point of care. Participants acknowledged the benefits of an EPaCCS to facilitate information sharing; however, they also raised concerns about confidentiality, and availability of the increased time and resources required to access and maintain such a system.

Conclusions: EPaCCS offer a potential solution to information sharing challenges in end-of-life care. However, our findings suggest that there are issues in the initiation and documentation of end-of-life discussions that must be addressed through investment in training in order to ensure that there is sufficient information regarding ACP to populate the system. There is a need for further qualitative research evaluating use of an EPaCCS, which explores benefits and challenges, uptake and reasons for disparities in use to better understand the potential utility and implications of such systems.
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http://dx.doi.org/10.1136/bmjopen-2020-037483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537426PMC
October 2020

Defining the Digital Self: A Qualitative Study to Explore the Digital Component of Professional Identity in the Health Professions.

J Med Internet Res 2020 09 29;22(9):e21416. Epub 2020 Sep 29.

McMaster Education Research, Innovation, and Theory (MERIT), Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.

Background: Recent medical education literature pertaining to professional identity development fails to reflect the impact social media has on professional identity theory. Social media is transforming the field of medicine, as the web-based medium is now an avenue for professional development and socialization for medical students and residents. Research regarding identity development in social media has been primarily confined to electronic professionalism through best practice guidelines. However, this neglects other potential aspects pertinent to digital identity that have not yet been explored.

Objective: This study aims to define the properties and development of the digital self and its interactions with the current professional identity development theory.

Methods: A qualitative study was conducted using thematic analysis. A total of 17 participants who are social media education and knowledge translation experts were interviewed. The initial participants were from emergency medicine, and a snowball sampling method was used following their respective web-based semistructured interviews to enable global recruitment of other participants from interprofessional disciplines. The research team consisted of a diverse group of researchers including one current social media knowledge translation physician clinician educator, one postdoctoral researcher who is regularly engaged in social media knowledge translation, and 3 nonphysician research assistants who are not social media users. Half of the team conducted the initial coding and analysis, whereas the other 2 investigators audited the procedures followed.

Results: A total of 4 themes were identified that pertain to digital identity. In the first theme, origins of initial digital identity formation were found to be derived from perceived needs in professional roles (eg, as a medical student or resident). The second theme consisted of the cultivation of digital identity, in which digital identity was developed parallel to professional identity. The third theme that emerged was the management between the professional and personal components of digital identity. Participants initially preferred keeping these components completely separate; however, attempts to do so were inadequate while the integration of both components provided benefits. The fourth theme was the management of real-life identity and digital identity. Participants preferred real-life identity to be wholly represented on the web. Instances of misalignment resulted in identity conflict, compromising one of the identities.

Conclusions: Social media introduces new features to professional identity in the digital world. The formation of digital identity, its development, and reconciliation with other identities were features captured in our analysis. The virtual component of professional identity must not be neglected but instead further explored, as educational institutions continue to give more importance to navigating professional identity development.
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http://dx.doi.org/10.2196/21416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556376PMC
September 2020

Reply: Breast Implant Illness, Biofilm, and the Role of Capsulectomy.

Authors:
Mark A Lee

Plast Reconstr Surg Glob Open 2020 Aug 14;8(8):e2994. Epub 2020 Aug 14.

St John of God Hospital, Subiaco, Perth, Western Australia, Australia.

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http://dx.doi.org/10.1097/GOX.0000000000002994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489741PMC
August 2020

Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19:Serologic Testing.

Clin Infect Dis 2020 Sep 12. Epub 2020 Sep 12.

Division of Nephrology and Hypertension, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.

Background: The availability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serologic testing has rapidly increased. Current assays use a variety of technologies, measure different classes of immunoglobulin or immunoglobulin combinations and detect antibodies directed against different portions of the virus. The overall accuracy of these tests, however, has not been well-defined. The Infectious Diseases Society of America (IDSA) convened an expert panel to perform a systematic review of the coronavirus disease 2019 (COVID-19) serology literature and construct best practice guidance related to SARS-CoV-2 serologic testing. This guideline is the fourth in a series of rapid, frequently updated COVID-19 guidelines developed by IDSA.

Objective: IDSA's goal was to develop evidence-based recommendations that assist clinicians, clinical laboratories, patients and policymakers in decisions related to the optimal use of SARS-CoV-2 serologic tests in a variety of settings. We also highlight important unmet research needs pertaining to the use of anti-SARS-CoV-2 antibody tests for diagnosis, public health surveillance, vaccine development and the selection of convalescent plasma donors.

Methods: A multidisciplinary panel of infectious diseases clinicians, clinical microbiologists and experts in systematic literature review identified and prioritized clinical questions related to the use of SARS-CoV-2 serologic tests. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations.

Results: The panel agreed on eight diagnostic recommendations.

Conclusions: Information on the clinical performance and utility of SARS-CoV-2 serologic tests are rapidly emerging. Based on available evidence, detection of anti-SARS-CoV-2 antibodies may be useful for confirming the presence of current or past infection in selected situations. The panel identified three potential indications for serologic testing including: 1) evaluation of patients with a high clinical suspicion for COVID-19 when molecular diagnostic testing is negative and at least two weeks have passed since symptom onset; 2) assessment of multisystem inflammatory syndrome in children; and 3) for conducting serosurveillance studies. The certainty of available evidence supporting the use of serology for either diagnosis or epidemiology was, however, graded as very low to moderate.
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http://dx.doi.org/10.1093/cid/ciaa1343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543294PMC
September 2020

Extensor Pollicis Longus Tendon Rupture After a Pediatric Distal Radius Fracture: A Case Report and Literature Review.

JBJS Case Connect 2020 Jul-Sep;10(3):e2000022

1Department of Orthopedic Surgery, University of Connecticut, Connecticut Children's Medical Center, Hartford, Connecticut.

Case: A 16-year-old boy underwent closed reduction and pinning of a Salter-Harris II distal radius fracture (DRF). Extensor pollicis longus (EPL) rupture occurred 6 weeks after the injury. Extensor indicis proprius transfer was performed using wide-awake local anesthesia no tourniquet (WALANT) technique. Active thumb range of motion was restored, and the patient returned to all activities, including sports, after 2 months.

Conclusion: Although delayed attritional EPL rupture after DRF is a well-known complication in adults, this is the first reported case in a truly skeletally immature patient. Awareness of this complication prompts monitoring for prodromal signs and symptoms. The WALANT technique is feasible in selected children.
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http://dx.doi.org/10.2106/JBJS.CC.20.00022DOI Listing
April 2021

Environmental and Aerosolized Severe Acute Respiratory Syndrome Coronavirus 2 Among Hospitalized Coronavirus Disease 2019 Patients.

J Infect Dis 2020 11;222(11):1798-1806

Division of Infectious Diseases, School of Medicine, Duke University, Durham, North Carolina, USA.

During April and May 2020, we studied 20 patients hospitalized with coronavirus disease 2019 (COVID-19), their hospital rooms (fomites and aerosols), and their close contacts for molecular and culture evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Among >400 samples, we found molecular evidence of virus in most sample types, especially the nasopharyngeal (NP), saliva, and fecal samples, but the prevalence of molecular positivity among fomites and aerosols was low. The agreement between NP swab and saliva positivity was high (89.5%; κ = 0.79). Two NP swabs collected from patients on days 1 and 7 post-symptom onset had evidence of infectious virus (2 passages over 14 days in Vero E6 cells). In summary, the low molecular prevalence and lack of viable SARS-CoV-2 virus in fomites and air samples implied low nosocomial risk of SARS-CoV-2 transmission through inanimate objects or aerosols.
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http://dx.doi.org/10.1093/infdis/jiaa575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499634PMC
November 2020

Teaching reaction kinetics through isomerization cases with the basis of density-functional calculations.

Biochem Mol Biol Educ 2021 Mar 8;49(2):216-227. Epub 2020 Sep 8.

Department of Physics, Faculty of Science, National University of Singapore, Singapore, Singapore.

The fundamental mechanism of biochemistry lies on the reaction kinetics, which is determined by the reaction pathways. Interestingly, the reaction pathway is a challenging concept for undergraduate students. Experimentally, it is difficult to observe, and theoretically, it requires some degree of physics knowledge, namely statistical and quantum mechanics. However, students can utilize computational methods to study the reaction kinetics without paying too much attention but not wholly neglecting the comprehension of physics. We hereby provided an approach to study the reaction kinetics based on density-functional calculations. We particularized the study of the isomerization case involving five molecules at three different temperatures and emphasized the importance of the transition state in the study of reaction kinetics. The results we presented were in good agreement with the experiments and provided useful insights to assist students in the application of their knowledge into their research.
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http://dx.doi.org/10.1002/bmb.21433DOI Listing
March 2021

Clinical impact of frailty on treatment outcomes of elderly patients with relapsed and/or refractory multiple myeloma treated with lenalidomide plus dexamethasone.

Int J Hematol 2021 Jan 5;113(1):81-91. Epub 2020 Sep 5.

Department of Internal Medicine, Seoul St. Mary's Hospital, Catholic University of Korea, 505, Banpo-dong, Seocho-gu, Seoul, 137-701, South Korea.

We compared efficacy and safety, according to frailty, of elderly patients with relapsed and refractory multiple myeloma (RRMM) treated with lenalidomide and dexamethasone (Rd), for whom bortezomib treatment had failed. Patients, 164 (52.9%) and 146 (47.1%), were classified as non-frail and frail using a simplified frailty scale. The overall response rates (ORR) and survival outcomes were lower in frail than in non-frail patients (ORR: 56.2% vs. 67.7%, P = 0.069; median progression free survival: 13.17 vs. 17.80 months, P = 0.033; median overall survival: 23.00 vs. 36.27 months, P = 0.002, respectively). The number of treatment emergent adverse events in grade 3 or worse was higher in frail than in non-frail patients (41.8% vs. 24.4%, P = 0.002, respectively). In frail patients, independent poor prognostic factors for survival were two or more Charlson comorbidity index (CCI) score, prior to exposure to both bortezomib and thalidomide, and achieved less than partial response In conclusion, frailty could predict clinical outcomes of Rd treatment in elderly patients with RRMM who had failed prior bortezomib. In frail patients, lower CCI in addition to less previous treatment exposure and deep response were associated with better survival.
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http://dx.doi.org/10.1007/s12185-020-02988-6DOI Listing
January 2021

SiGe microelectronic thermoelectric generators with high power and voltage densities.

Nat Commun 2020 Aug 31;11(1):4362. Epub 2020 Aug 31.

Department of Physics, The University of Texas at Dallas, Richardson, TX, 75080, USA.

Microelectronic thermoelectric generators are one potential solution to energizing energy autonomous electronics, such as internet-of-things sensors, that must carry their own power source. However, thermoelectric generators with the mm footprint area necessary for on-chip integration made from high thermoelectric figure-of-merit materials have been unable to produce the voltage and power levels required to run Si electronics using common temperature differences. We present microelectronic thermoelectric generators using SiGe, made by standard Si processing, with high voltage and power generation densities that are comparable to or better than generators using high figure-of-merit materials. These Si-based thermoelectric generators have <1 mm areas and can energize off-the-shelf sensor integrated circuits using temperature differences ≤25 K near room temperature. These generators can be directly integrated with Si circuits and scaled up in area to generate voltages and powers competitive with existing thermoelectric technologies, but in what should be a far more cost-effective manner.
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http://dx.doi.org/10.1038/s41467-020-18122-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458905PMC
August 2020