Sharing Data from the Human Tumor Atlas Network through Standards, Infrastructure, and Community Engagement.

The Data Coordinating Center (DCC) of the Human Tumor Atlas Network (HTAN) has played a crucial role in enabling the broad sharing and effective utilization of HTAN data within the scientific community. Data from the first phase of HTAN are now available publicly. We describe the diverse datasets and modalities shared, multiple access routes to HTAN assay data and metadata, data standards, technical infrastructure and governance approaches, as well as our approach to sustained community engagement. HTAN data can be accessed via the HTAN Portal, explored in visualization tools-including CellxGene, Minerva, and cBioPortal-and analyzed in the cloud through the NCI Cancer Research Data Commons nodes. We have developed a streamlined infrastructure to ingest and disseminate data by leveraging the Synapse platform. Taken together, the HTAN DCC's approach demonstrates a successful model for coordinating, standardizing, and disseminating complex cancer research data via multiple resources in the cancer data ecosystem, offering valuable insights for similar consortia, and researchers looking to leverage HTAN data.

Pediatric Burns - Who Requires Follow-up? A Study of Urban Pediatric Emergency Department Patients.

Introduction: Hundreds of children suffer burn injuries each day, yet care guidelines regarding the need for acute inpatient treatment vs outpatient follow-up vs no required follow-up remain nebulous. This gap in the literature is particularly salient for the emergency clinician, who must be able to rapidly determine appropriate disposition. Methods: This was a retrospective review of patients presenting to a Level II pediatric trauma center, January 1, 2017-December 31, 2019, and discharged with an International Classification of Diseases, Rev 10, burn diagnosis. We obtained and analyzed demographics, burn characteristics, and follow-up data using univariate and bivariate analysis as well as logistic regression modeling. Patients were stratified into three outcome groups: group 1-patients who underwent emergent evaluation at a burn center or were admitted at their first follow-up appointment; group 2-patients who followed up at a burn center (as an outpatient) or at the emergency department (and were discharged home); and group 3-patients with no known follow-up. Results: A total of 572 patients were included in this study; 58.9% of patients were 1-5 years of age. Sixty-five patients met group 1 criteria, 189 patients met group 2 criteria, and 318 patients met group 3 criteria. Sixty-five percent of patients met at least one American Burn Association criteria, and 79% of all burns were second-degree burns. Flame and scald burns were associated with increased odds (odds ratio [OR] 1.21, OR 1.12) of group 1 vs group 2 + group 3 (P = 0.02, P < 0.001). Second/third-degree burns and concern for non-accidental trauma were also associated with increased odds of group 1 vs 2 or 3 (OR = 1.11, 1.35, P ≤ 0.001, 0.001, respectively). Scald burns were associated with increased odds of group 2 compared to group 3 (OR 1.11, P = 0.04). Second/third degree burns were also associated with increased odds of group 2 vs 3 (OR 1.19, P ≤ 0.001). Conclusion: There were few statistically significant variables strongly associated with group 1 (emergent treatment/admission) vs group 2 (follow-up/outpatient treatment) vs group 3 (no follow- up). However, one notable finding in this study was the association of scald burns with treatment (admission or follow-up) suggesting that the presence of a scald burn in a child may signify to clinicians that a burn center consult is warranted.

Microbial etiology of vertebral osteomyelitis/discitis amid the opioid epidemic.

OBJECTIVE: The primary goal of this study was to establish the current microbial trends in vertebral osteomyelitis/discitis (VOD) amid the opioid epidemic and to determine if intravenous drug use (IVDU) predisposes one to a unique microbial profile of infection. METHODS: The authors performed a retrospective cohort study consisting of 1175 adult patients diagnosed with VOD between 2011 and 2022 at a single quaternary center. Data were acquired through retrospective chart review, with pertinent demographic and clinical information collected. RESULTS: Staphylococcus aureus was the most cultured organism in both the IVDU and non-IVDU groups at 56.1% and 40.7%, respectively. In the IVDU cohort, Serratia marcescens was the next most prevalently cultured organism at 13.9%. CONCLUSIONS: The present study demonstrates that in the IVDU population S. marcescens is an organism of high concern. The potential for Serratia spp. infection should be accounted for when selecting empirical antimicrobial therapy in VOD patients.

Anatomic Total Shoulder Arthroplasty Outcomes Were Not Negatively Affected by the COVID-19 Pandemic.

Objective To investigate whether patients undergoing anatomic total shoulder arthroplasty (ATSA) between January and March 2020 experienced different postoperative outcomes than patients in 2019. We hypothesized that patients in 2020 would have less access to physical therapy (PT) and experience different postoperative outcomes. Methods Records from patients who received ATSA between January 1st, 2019, and March 17th, 2019, and January 1st, 2020, to March 17th, 2020, were analyzed. Patient data, including demographic information, range of motion (ROM), strength, and PT was collected and compared between the two groups. The 2020 patients were contacted by phone during October 2022 and patient-reported metrics were gathered. Results The present study identified 24 patients in 2019 and 27 patients in 2020 who underwent ATSA during the specified time frame and had a minimum 1-year follow-up. Patients in 2019 experienced improvements in forward elevation (FE) ROM (125.4° to 146.7°; p = 0.008), external rotation (ER; 33.0° to 47.7°; p < 0.001), and internal rotation (IR; S1 to L4; p = 0.019). Patients in 2020 also experienced significant improvements in FE (120.2° to 141.1°; p = 0.009), ER (32.9° to 42.0°; p = 0.037), and IR (S1 to L3; p = 0.002). Patients in 2020 terminated PT earlier (2019: 125.8 days; 2020: 91.1 days; p = 0.046) and completed fewer sessions (2019: 21.4 sessions; 2020: 13.1 sessions; p = 0.003). At the final follow-up, patients in 2020 reported an average Visual Analogue Scale (VAS) pain score of 1.67 ± 1.1. Conclusion Despite decreased PT, patients who underwent ATSA in 2020 had significant improvements in ROM and strength and were comparable to patients in 2019.

Anatomic Total Shoulder Arthroplasty Outcomes Were Not Negatively Affected by the COVID-19 Pandemic / Os desfechos da artroplastia anatômica total do ombro não foram afetados negativamente pela pandemia de Covid-19

Abstract Objective To investigate whether patients undergoing anatomic total shoulder arthroplasty (ATSA) between January and March 2020 experienced different postoperative outcomes than patients in 2019. We hypothesized that patients in 2020 would have less access to physical therapy (PT) and experience different postoperative outcomes. Methods Records from patients who received ATSA between January 1st, 2019, and March 17th, 2019, and January 1st, 2020, to March 17th, 2020, were analyzed. Patient data, including demographic information, range of motion (ROM), strength, and PT was collected and compared between the two groups. The 2020 patients were contacted by phone during October 2022 and patient-reported metrics were gathered. Results The present study identified 24 patients in 2019 and 27 patients in 2020 who underwent ATSA during the specified time frame and had a minimum 1-year follow-up. Patients in 2019 experienced improvements in forward elevation (FE) ROM (125.4° to 146.7°; p = 0.008), external rotation (ER; 33.0° to 47.7°; p < 0.001), and internal rotation (IR; S1 to L4; p = 0.019). Patients in 2020 also experienced significant improvements in FE (120.2° to 141.1°; p = 0.009), ER (32.9° to 42.0°; p = 0.037), and IR (S1 to L3; p = 0.002). Patients in 2020 terminated PT earlier (2019: 125.8 days; 2020: 91.1 days; p = 0.046) and completed fewer sessions (2019: 21.4 sessions; 2020: 13.1 sessions; p = 0.003). At the final follow-up, patients in 2020 reported an average Visual Analogue Scale (VAS) pain score of 1.67 ± 1.1. Conclusion Despite decreased PT, patients who underwent ATSA in 2020 had significant improvements in ROM and strength and were comparable to patients in 2019.

Resumo Objetivo Investigar se os pacientes submetidos à artroplastia total anatômica do ombro (ATAO) entre janeiro e março de 2020 tiveram resultados pós-operatórios diferentes dos pacientes operados em 2019. Nossa hipótese é a de que os pacientes de 2020 teriam menos acesso à fisioterapia (FT) e apresentariam desfechos pós-opera-tórios diferentes. Métodos Foram analisados os prontuários de pacientes submetidos à ATAO de 1° de janeiro de 2019 a 17 de março de 2019 e de 1° de janeiro de 2020 a 17 de março de 2020. Os dados dos pacientes, incluindo informações demográficas, amplitude de movimento (ADM), força e FT foram coletados e comparados entre os dois grupos. Os pacientes de 2020 foram contatados por telefone durante outubro de 2022, e as métricas relatadas por eles pacientes foram coletadas. Resultados Este estudo identificou 24 pacientes em 2019 e 27 pacientes em 2020 que foram submetidos à ATAO durante o período especificado e tiveram acompanhamento mínimo de 1 ano. Os pacientes em 2019 apresentaram melhoras na ADM de elevação anterior (EA; 125,4° a 146,7°; p = 0,008), rotação externa (RE; 33,0° a 47,7°; p < 0,001) e rotação interna (RI; S1 a L4; p = 0,019). Os pacientes em 2020 também apresentaram melhoras significativas de EA (120,2° a 141,1°; p = 0,009), RE (32,9° a 42,0°; p = 0,037) e RI (S1 a L3; p = 0,002). Os pacientes de 2020 terminaram a FT mais cedo (2019: 125,8 dias; 2020: 91,1 dias; p = 0,046) e fizeram menos sessões (2019: 21,4 sessões; 2020: 13,1 sessões; p = 0,003). No acompanhamento final, os pacientes de 2020 relataram uma pontuação média de dor na Escala Visual Analógica (EVA) de 1,67 ± 1,1. Conclusão Apesar da menor realização de FT, os pacientes submetidos à ATAO em 2020 apresentaram melhoras significativas na ADM e na força e foram comparáveis aos pacientes de 2019.

Blood Vitamin C Levels of Patients Receiving Immunotherapy and Relationship to Monocyte Subtype and Epigenetic Modification.

The treatment of metastatic melanoma has been revolutionised by immunotherapy, yet a significant number of patients do not respond, and many experience autoimmune adverse events. Associations have been reported between patient outcome and monocyte subsets, whereas vitamin C (ascorbate) has been shown to mediate changes in cancer-stimulated monocytes in vitro. We therefore investigated the relationship of ascorbate with monocyte subsets and epigenetic modifications in patients with metastatic melanoma receiving immunotherapy. Patients receiving immunotherapy were compared to other cancer cohorts and age-matched healthy controls. Ascorbate levels in plasma and peripheral blood-derived mononuclear cells (PBMCs), monocyte subtype and epigenetic markers were measured, and adverse events, tumour response and survival were recorded. A quarter of the immunotherapy cohort had hypovitaminosis C, with plasma and PBMC ascorbate levels significantly lower than those from other cancer patients or healthy controls. PBMCs from the immunotherapy cohort contained similar frequencies of non-classical and classical monocytes. DNA methylation markers and intracellular ascorbate concentration were correlated with monocyte subset frequency in healthy controls, but correlation was lost in immunotherapy patients. No associations between ascorbate status and immune-related adverse events or tumour response or overall survival were apparent.

Amphiregulin Switches Progenitor Cell Fate for Lineage Commitment During Gastric Mucosal Regeneration.

BACKGROUND & AIMS: Isthmic progenitors, tissue-specific stem cells in the stomach corpus, maintain mucosal homeostasis by balancing between proliferation and differentiation to gastric epithelial lineages. The progenitor cells rapidly adopt an active state in response to mucosal injury. However, it remains unclear how the isthmic progenitor cell niche is controlled during the regeneration of damaged epithelium. METHODS: We recapitulated tissue recovery process after acute mucosal injury in the mouse stomach. Bromodeoxyuridine incorporation was used to trace newly generated cells during the injury and recovery phases. To define the epithelial lineage commitment process during recovery, we performed single-cell RNA-sequencing on epithelial cells from the mouse stomachs. We validated the effects of amphiregulin (AREG) on mucosal recovery, using recombinant AREG treatment or AREG-deficient mice. RESULTS: We determined that an epidermal growth factor receptor ligand, AREG, can control progenitor cell lineage commitment. Based on the identification of lineage-committed subpopulations in the corpus epithelium through single-cell RNA-sequencing and bromodeoxyuridine incorporation, we showed that isthmic progenitors mainly transition into short-lived surface cell lineages but are less frequently committed to long-lived parietal cell lineages in homeostasis. However, mucosal regeneration after damage directs the lineage commitment of isthmic progenitors towards parietal cell lineages. During recovery, AREG treatment promoted repopulation with parietal cells, while suppressing surface cell commitment of progenitors. In contrast, transforming growth factor-α did not alter parietal cell regeneration, but did induce expansion of surface cell populations. AREG deficiency impairs parietal cell regeneration but increases surface cell commitment. CONCLUSIONS: These data demonstrate that different epidermal growth factor receptor ligands can distinctly regulate isthmic progenitor-driven mucosal regeneration and lineage commitment.

CT guided biopsy for osteodiscitis reduces cost of hospitalization in the landscape of increasing intravenous drug use: A single center retrospective analysis.

OBJECTIVE: Osteodiscitis has been demonstrated to show significant morbidity and mortality. Cultures and CT guided biopsy (CTB) are commonly used diagnosis of osteodiscitis. This study's purpose is to evaluate the cost burden of CTB and to evaluate how IVDU affects patient management in the setting of osteodiscitis. METHODS: Patients admitted for osteodiscitis from 2011-2021 were retrospectively reviewed and stratified into cohorts by CTB status. Additional cohorts were stratified by Intravenous Drug Use (IVDU). Patient demographics, total cost of hospitalization, length of hospitalization, time to biopsy, IVDU status, and other factors were recorded. T-Test, Chi-squared analysis, and ANOVA were used for statistical analysis. RESULTS: Total cost of hospitalization was recorded for 140 patients without CTB and 346 patients with CTB. Average cost of hospitalization for non-CTB was $227,317.86 compared to CTB at $119,799.20 (p < 0.001). Length of stay (LOS) was found to be 18.01 days for non-CTB and 14.07 days for CTB patients (0.00282). When stratified by days until biopsy, patients who had CTB sooner, had significantly reduced cost of hospitalization (p = 0.0003). Patients with IVDU history were significantly younger (p < 0.001) with lower BMI (p < 0.001) and a significantly different clinical profile. There was a significant difference in positive open biopsy when separated by IVDU status (p = 0.025). CONCLUSION: CTB was associated with significantly reduced cost of hospitalization and LOS compared to non-CTB. IVDU patients with osteodiscitis have significantly different clinical profiles than non-IVDU that may impact diagnosis and treatment. Further work is indicated to elucidate causes of these differences to provide high value care to patients with osteodiscitis.

Impact of obesity on adult spinal deformity (ASD) long-segment spinal fusion radiographic and clinical outcomes.

STUDY DESIGN: Retrospective chart review of patients receiving long-segment fusion during a five-year period. OBJECTIVE: To determine whether obese patients receive comparable benefits when receiving long-segment fusion compared to non-obese patients and to identify factors that may predict hardware failure and post-surgical complications among obese patients. METHODS: Demographic, spinopelvic radiographic, patient-reported outcome measures (PROMs), and complications data was retrospectively collected from 120 patients who underwent long-segment fusion during a five-year period at one tertiary care medical center. Radiographic measurements were pelvic incidence, pelvic tilt (PT), lumbar lordosis, L4-S1 lordosis, thoracic kyphosis, sagittal vertical axis, PI-LL mismatch, and proximal junction cobb angle at upper instrumented vertebrae + 2 (UIV+2). PROMs were Oswestry disability index, numeric rating scale (NRS) Back Pain, NRS Leg Pain, RAND SF-36 pain, and RAND SF-36 physical functioning. Included patients were adults and had at least 2-years of postoperative follow-up. Descriptive and multivariate statistical analysis was performed with α = 0.05. RESULTS: Patients with a BMI ≥ 30 (n=63) and patients with a BMI < 30 (n=57) demonstrated comparable improvements (P>0.05) for all spinopelvic radiographic measurements and PROMs. Each cohort demonstrated significant improvements from pre-assessment to post-assessment on nearly all spinopelvic radiographic measurements and PROMs (P<0.05), except PT and L4-S1 lordosis where neither group improved (p=0.95 and 0.58 for PT and P=0.23 and 0.11 for L4-S1 lordosis fornon-obese and obese cohorts respectively) and SF-36 physical functioning where the non-obese cohort not statistically improve (P=0.08). Patients with a BMI ≥ 30 demonstrated an increased incidence of cardiovascular complications (P=0.0293), acute kidney injury (P=0.0241), rod fractures (P=0.0293), and reoperations (P=0.0241) when compared to patients with a BMI < 30. CONCLUSION: This study adds to a growing body of evidence linking demographic factors with risks of hardware failure. Further, this data challenges the assumption that obese patients may not receive sufficient benefit to be long-segment surgical candidates. However, given their elevated risk for post-operative and delayed hardware complications, obese patients should be appropriately counseling before undergoing surgery.

Health information management and physiotherapy faculty collaboration to discover the use of health informatics hiding in plain sight in an entry-level DPT program.

Background: Many educational disciplines, especially in health professions, are required by accrediting bodies to introduce or include health informatics (HI); however, faculty (academics) teaching this content may not be well prepared. Objective: The aim of this project was to explore how a doctoral physical therapy (DPT) program could more accurately represent compliance with HI accreditation requirements by identifying hidden instances of relevant content within the curriculum. Method: This exploratory, mixed methods, action research study utilised document review, questionnaires and interviews in the collection of quantitative and qualitative data to enable assessment of knowledge about HI, to determine if HI content was already incorporated in current courses, and, whether the content was accurately reflected in course student learning objectives (SLOs). Change in faculty understanding of HI as a result of this study was also assessed. Results: Of 16 DPT faculty, 13 participated in the pre-interview questionnaire; 8 (50%) representing 22/39 courses participated in the full study. Most were unfamiliar with HI and had unrecognised HI already incorporated in their courses leading to several SLO revisions and additions. Interview and post-interview questionnaire results documented significant increases in HI understanding among faculty. Conclusion: Physical therapy and HIM collaboration was successful in identifying HI content hiding in plain sight. Results revealed multiple instances of unrecognised HI content across the DPT curriculum. Revised and newly added SLOs, with others likely to follow due to this study, will assist faculty with future reaccreditation and in preparing graduates to more fully utilise HI in today's digital healthcare environments.

Utility of prophylactic closed suction drainage in open reduction and internal fixation for tibial plateau fracture.

PURPOSE: The usefulness of closed suction drains (CSD) after open reduction and internal fixation (ORIF) of tibial plateau fractures is a contested topic. The purpose of this study was to examine the impact of CSD in postoperative outcomes after tibial plateau fracture. METHODS: Data were retrospectively collected from patients who underwent primary repair of closed tibial plateau fractures via an anterolateral approach between June 2021 to May 2022 at a single academic center. Fifty-six patients were included and 28 received CSDs at time of surgery. P values less than 0.05 were considered significant. RESULTS: Fifty-six patients were included. There was no significant difference in demographics, pre- and post-op hemoglobin, estimated blood loss during surgery, length of stay, postoperative MMEs and pain at 3 month follow-up, deep vein thrombosis (DVT), compartment syndrome, flexion contracture, use of incisional vac, infection rate, wound drainage, hematoma, neurologic pain, dehiscence, additional surgery, or range of motion at 3 months follow-up. We noted a significant difference in Defense and Veterans Pain Rating Scale (DVPRS) on POD1, demonstrating greater pain in those in the CSD group. CONCLUSION: Our findings suggest that the use of CSD in ORIF of tibial plateau fractures may not be of significant prophylactic benefit. CSDs in ORIF patients were associated with increased early postoperative pain and had no identifiable benefits. LEVEL OF EVIDENCE: III.

Use of global sagittal flexibility to predict proximal junctional kyphosis after spinal deformity surgery.

OBJECTIVE: Sagittal alignment is an important predictor of functional outcomes after surgery for adult spinal deformity (ASD). A rigid spinal column may create a large lever arm that may impact the rate of proximal junctional kyphosis (PJK) after ASD surgery. In this study, the authors sought to determine whether relatively low preoperative global spinal flexibility (i.e., rigid spine) predicts increased incidence of PJK at 1 year after ASD surgery. METHODS: The authors retrospectively reviewed long-segment thoracolumbar fusions with pelvic fixation performed at a single tertiary care center between October 2015 and September 2020 in patients with a minimum of 1-year radiographic and clinical follow-up. Two cohorts were established on the basis of the optimal value for spinal flexibility, as defined by the absolute difference between the preoperative standing and supine C7 sagittal vertical axes, which the authors termed global sagittal flexibility (GSF). Demographic information, radiographs, various associated complications, and patient-reported outcome measures (PROMs) were analyzed. RESULTS: Eighty-five patients met the inclusion criteria. Receiver operating characteristic (ROC) analysis using GSF to predict an increase in the proximal junctional sagittal Cobb angle (PJCA) greater than or equal to 10° at 1-year follow-up provided an area under the curve of 0.64 and identified an optimal GSF threshold value of 3.7 cm. Patients with GSF > 3.7 cm were considered globally flexible (48 patients), and those with GSF ≤ 3.7 cm were classified as rigid (37 patients). Rigid patients were noted to have a significantly higher risk of ΔPJCA ≥ 10° at 1-year follow-up (51.4% vs 29.3%, p = 0.049). No changes in the reoperation rates or PROMs based on GSF were observed in the 1- or 2-year postoperative window. CONCLUSIONS: Based on these retrospective data, preoperative global spinal rigidity portends an independently elevated risk for the development of PJK after ASD surgery. No differences in other complication rates or PROMs data were observed between groups. Data collection was limited to a 2-year postoperative window; therefore, longer follow-up is required to further elucidate the relationship between rigidity and reoperation rates. Based on these retrospective data, flexibility may influence the outcomes of patients with ASD.

National Cancer Institute Imaging Data Commons: Toward Transparency, Reproducibility, and Scalability in Imaging Artificial Intelligence.

The remarkable advances of artificial intelligence (AI) technology are revolutionizing established approaches to the acquisition, interpretation, and analysis of biomedical imaging data. Development, validation, and continuous refinement of AI tools requires easy access to large high-quality annotated datasets, which are both representative and diverse. The National Cancer Institute (NCI) Imaging Data Commons (IDC) hosts large and diverse publicly available cancer image data collections. By harmonizing all data based on industry standards and colocalizing it with analysis and exploration resources, the IDC aims to facilitate the development, validation, and clinical translation of AI tools and address the well-documented challenges of establishing reproducible and transparent AI processing pipelines. Balanced use of established commercial products with open-source solutions, interconnected by standard interfaces, provides value and performance, while preserving sufficient agility to address the evolving needs of the research community. Emphasis on the development of tools, use cases to demonstrate the utility of uniform data representation, and cloud-based analysis aim to ease adoption and help define best practices. Integration with other data in the broader NCI Cancer Research Data Commons infrastructure opens opportunities for multiomics studies incorporating imaging data to further empower the research community to accelerate breakthroughs in cancer detection, diagnosis, and treatment. Published under a CC BY 4.0 license.

Psychological Factors That Affect Return to Sport After Surgical Intervention for Shoulder Instability: A Systematic Review.

Background: Recent advances have begun to identify the nonphysical factors facilitating successful return to sport (RTS) after shoulder instability surgery, yet little is currently known regarding psychological factors and RTS. Purpose/Hypothesis: The purposes of this study were to (1) identify psychological factors associated with RTS, (2) evaluate the prognostic utility of various psychological factors, and (3) evaluate the available metrics used to assess psychological RTS readiness. It was hypothesized that psychological factors would be identified as critical elements influencing a patient's RTS. Study Design: Systematic review; Level of evidence, 4. Methods: Clinical studies reporting on the psychological determinants of RTS for patients who had surgery for shoulder instability between 1996 and 2022 were identified from MEDLINE, Embase, and Cochrane databases. Demographic, clinical, and psychometric properties were extracted for pooled weighted analysis. Results: Of the 969 studies screened, 24 (2.5%) met inclusion criteria. Overall, 2135 patients were included (mean age, 26.0 years; range, 17.4-35.5 years; 84.7% male). The mean time to RTS was 6.8 months (range, 3.7-11.9 months). There was a 76.3% rate of any RTS; of the 1212 patients who reported level of play at return, 305 (25.2%) were unable to perform at their prior level. Psychological reasons were cited by 85% (n = 360) of patients who did not RTS. Fear of reinjury was the most common reason (n = 154; 42.8%); other psychological factors included lack of confidence (n = 46; 12.8%), anxiety (n = 45; 12.5%), depression (n = 44; 12.2%), psychosocial factors (n = 48; 13.3%), and lack of motivation (n = 23; 6.4%). The Shoulder Instability Return to Sport after Injury, Western Ontario Shoulder Instability Index, Quick Inventory of Depressive Symptoms Self Report, Degree of Shoulder Involvement in Sports, Tampa Scale of Kinesiophobia-11, and Veterans Rand 12-Item Health Survey were reported measures for assessing psychology and RTS. Conclusion: Fear of reinjury was found to be the most commonly reported impediment to RTS. The psychological characteristics identified through this review may be incorporated into future RTS protocols seeking to address resilience and nonphysical factors associated with RTS.

Mind the gap: reconciling tropical forest carbon flux estimates from earth observation and national reporting requires transparency.

BACKGROUND: The application of different approaches calculating the anthropogenic carbon net flux from land, leads to estimates that vary considerably. One reason for these variations is the extent to which approaches consider forest land to be "managed" by humans, and thus contributing to the net anthropogenic flux. Global Earth Observation (EO) datasets characterising spatio-temporal changes in land cover and carbon stocks provide an independent and consistent approach to estimate forest carbon fluxes. These can be compared against results reported in National Greenhouse Gas Inventories (NGHGIs) to support accurate and timely measuring, reporting and verification (MRV). Using Brazil as a primary case study, with additional analysis in Indonesia and Malaysia, we compare a Global EO-based dataset of forest carbon fluxes to results reported in NGHGIs. RESULTS: Between 2001 and 2020, the EO-derived estimates of all forest-related emissions and removals indicate that Brazil was a net sink of carbon (- 0.2 GtCO2yr-1), while Brazil's NGHGI reported a net carbon source (+ 0.8 GtCO2yr-1). After adjusting the EO estimate to use the Brazilian NGHGI definition of managed forest and other assumptions used in the inventory's methodology, the EO net flux became a source of + 0.6 GtCO2yr-1, comparable to the NGHGI. Remaining discrepancies are due largely to differing carbon removal factors and forest types applied in the two datasets. In Indonesia, the EO and NGHGI net flux estimates were similar (+ 0.6 GtCO2 yr-1), but in Malaysia, they differed in both magnitude and sign (NGHGI: -0.2 GtCO2 yr-1; Global EO: + 0.2 GtCO2 yr-1). Spatially explicit datasets on forest types were not publicly available for analysis from either NGHGI, limiting the possibility of detailed adjustments. CONCLUSIONS: By adjusting the EO dataset to improve comparability with carbon fluxes estimated for managed forests in the Brazilian NGHGI, initially diverging estimates were largely reconciled and remaining differences can be explained. Despite limited spatial data available for Indonesia and Malaysia, our comparison indicated specific aspects where differing approaches may explain divergence, including uncertainties and inaccuracies. Our study highlights the importance of enhanced transparency, as set out by the Paris Agreement, to enable alignment between different approaches for independent measuring and verification.

Single-cell gene set scoring with nearest neighbor graph smoothed data (gssnng).

Summary: Gene set scoring (or enrichment) is a common dimension reduction task in bioinformatics that can be focused on the differences between groups or at the single sample level. Gene sets can represent biological functions, molecular pathways, cell identities, and more. Gene set scores are context dependent values that are useful for interpreting biological changes following experiments or perturbations. Single sample scoring produces a set of scores, one for each member of a group, which can be analyzed with statistical models that can include additional clinically important factors such as gender or age. However, the sparsity and technical noise of single-cell expression measures create difficulties for these methods, which were originally designed for bulk expression profiling (microarrays, RNAseq). This can be greatly remedied by first applying a smoothing transformation that shares gene measure information within transcriptomic neighborhoods. In this work, we use the nearest neighbor graph of cells for matrix smoothing to produce high quality gene set scores on a per-cell, per-group, level which is useful for visualization and statistical analysis. Availability and implementation: The gssnng software is available using the python package index (PyPI) and works with Scanpy AnnData objects. It can be installed using "pip install gssnng." More information and demo notebooks: see https://github.com/IlyaLab/gssnng.

Levels and in vitro functional effects of circulating anti-hinge antibodies in melanoma patients receiving the immune checkpoint inhibitor pembrolizumab.

The efficacy of PD-1 monoclonals such as pembrolizumab can be modulated by the signals delivered via their Fc region. Tumour/inflammation associated proteases can generate F(ab')2 fragments of therapeutic monoclonals, and subsequent recognition of F(ab')2 epitopes by circulating anti-hinge antibodies (AHA) can then, potentially, link F(ab')2 binding to the target antigen with novel Fc signalling. Although elevated in inflammatory diseases, AHA levels in cancer patients have not been investigated and functional studies utilising the full repertoire of AHA present in sera have been limited. AHA levels in pembrolizumab treated melanoma patients (n = 23) were therefore compared to those of normal donors and adalimumab treated patients. A subset of melanoma patients and the majority of adalimumab patients had elevated levels of AHA reactive with F(ab')2 fragments of IgG4 anti-PD-1 monoclonals (nivolumab, pembrolizumab) and IgG1 therapeutic monoclonals (rituximab, adalimumab). Survival analysis was restricted by the small patient numbers but those melanoma patients with the highest levels (>75% percentile, n = 5) of pembrolizumab-F(ab')2 reactive AHA had significantly better overall survival post pembrolizumab treatment (p = 0.039). In vitro functional studies demonstrated that the presence of AHA+ sera restored the neutrophil activating capacity of pembrolizumab to its F(ab')2 fragment. Neither pembrolizumab nor its F(ab')2 fragments can induce NK cell or complement dependent cytotoxicity (CDC). However, AHA+ sera in combination with pembrolizumab-F(ab')2 provided Fc regions that could activate NK cells. The ability of AHA+ sera to restore CDC activity was more restricted and observed using only one pembrolizumab and one adalimumab patient serum in combination with rituximab- F(ab')2. This study reports the presence of elevated AHA levels in pembrolizumab treated melanoma patients and highlight the potential for AHA to provide additional Fc signaling. The issue of whether tumour associated proteolysis of PD-1 mAbs and subsequent AHA recognition impacts on treatment efficacy requires further study.

Horizontal Cleavage Meniscus Tears: Biomechanics, Indications, Techniques, and Outcomes.

¼ Accounting for up to 24% of all meniscus tears, horizontal cleavage tears (HCTs) are a common pathology orthopaedic practitioners should be comfortable managing.¼ Historically, HCTs were treated with partial meniscectomy; however, recent studies have demonstrated that these procedures have an adverse biomechanical effect, while HCT repairs restore the knee's natural biomechanics.¼ Indications for the surgical repair of HCTs remain disputed, but surgery is generally considered for young, active patients and older patients without significant concomitant osteoarthritis.¼ Early clinical findings surrounding HCT repair are promising. They suggest that this treatment adequately restores meniscus mechanics, leads to good knee functional outcomes, and results in a high likelihood of return to preinjury activity levels.

Promotion of higher rates of early fusion using activated titanium versus polyetheretherketone cages in adults undergoing 1- and 2-level transforaminal lumbar interbody fusion procedures: a randomized controlled trial.

OBJECTIVE: There is ongoing debate on the relative benefits and drawbacks of polyetheretherketone (PEEK) versus titanium (Ti) in generating a bone-to-implant surface microenvironment conducive to osseointegration. Micro- and nanoscale internal and topographic cage modifications have recently been posited to facilitate osseointegration and fusion, but human in vivo confirmation remains lacking. The authors of this study sought to directly compare early radiological outcomes in adults undergoing 1- and 2-level transforaminal lumbar interbody fusion (TLIF) procedures using either PEEK or nano-etched Ti interbody cages with an incorporated microlattice structure. METHODS: Patients were enrolled in a single academic center using a single-blind randomized controlled superiority design. Screening was undertaken from a pool of consecutive patients eligible for TLIF to undergo placement in a 1:1 ratio of either lordotic PEEK or activated Ti cages at each level of 1- or 2-level procedures. An a priori power analysis was performed and a preplanned interim analysis was undertaken once 50 of 70 patients were enrolled. Patient study data were collected perioperatively and uploaded to a Research Electronic Data Capture (REDCap) registry. Interbody fusion was assessed based on 6-month postoperative lumbar dual-energy CT (DECT) studies using the method of Brantigan and Steffee, as modified to describe the Fraser definition of locked pseudarthrosis (Brantigan-Steffee-Fraser [BSF] scale). RESULTS: In the final cohort of 50 patients, 40 interbody levels implanted with PEEK cages were compared with 34 interbody levels with activated Ti cages. The trial was stopped early given the results of an interim analysis with respect to the primary outcome. Surgical parameters including number of levels treated, average cage height, and position were not different between groups. For the PEEK and activated Ti groups, 20.6% versus 84.0% demonstrated BSF grade 3 fusion on 6-month postoperative DECT imaging (p < 0.001). Subsidence at 6 months on DECT was identified in 12 (41.4%) of PEEK levels versus 5 (20.8%) of activated Ti levels (p < 0.001). BSF-3 grading was predictive of segmental stability and numeric rating scale (NRS) leg pain improvement at 1 year postoperatively. Oswestry Disability Index and NRS back and leg pain scores all improved similarly in both cohorts at 1 year postoperatively. CONCLUSIONS: Activated Ti interbody cages mediate early fusion at significantly higher rates with lower rates of subsidence as compared with PEEK cages. These findings support the idea that interbody cage microscale properties, including surface topography, may play a primary role in facilitating osseointegration and fusion.

Association between systemic treatment with immune checkpoint inhibitor therapy in renal cell carcinoma and reduced risk of brain metastasis development.

OBJECTIVE: Immune checkpoint inhibitor (ICI) efficacy in the treatment of metastatic renal cell carcinoma (RCC) without brain metastases (BMs) is well established in several clinical trials; however, patients with BMs were typically excluded from these trials. Therefore, the efficacy of ICI in the treatment or prevention of BM remains unclear. The primary aim of the study was to address the efficacy of ICI in treatment of patients with RCC BMs compared with patients receiving targeted therapies. A secondary aim was to evaluate the risk of RCC BM development among patients who received ICI versus targeted therapies early in their treatment course. METHODS: A retrospective single-center review between 2011 and 2018 identified 425 patients treated for metastatic RCC. The study group included patients who received ICI and/or targeted therapies during their disease. Data analyzed included demographic information, systemic treatments, overall survival from RCC diagnosis (OSRCC) and from BM diagnosis (OSBM), and BM development. Fisher's exact test was used to evaluate the frequency of BM occurrence. Survival was assessed using Kaplan-Meier curves and log-rank tests. RESULTS: Of the 425 patients, 125 received ICI and 300 were treated with molecular targeted agents only during their clinical course. BMs occurred in 113 (9.5%) of the 425 patients. Among patients with BMs, OSRCC was improved with the use of ICI (77.2 vs 25.2 months, p < 0.001), with 1-, 2-, and 5-year survival rates of 93.9%, 81.8%, and 62.6%, respectively. The use of ICI was associated with increased OSBM (21.7 vs 8.9 months, p = 0.001). The rate of BM development was lower when patients were treated with ICI (8/100 [8.0%]) compared with targeted therapy (47/267 [17.6%]) (OR 0.41, 95% CI 0.18-0.89; p = 0.021). CONCLUSIONS: ICI was associated with improved OSRCC and OSBM in patients with BMs and decreased the probability of BM development in patients with metastatic RCC. Prospective trials are needed to further evaluate optimal use of ICI in treatment of RCC BMs.