Undergoing an Arthroscopic Procedure Prior to Shoulder Arthroplasty is Associated With Greater Risk of Prosthetic Joint Infection.

PURPOSE: To utilize a national all-payer claims dataset to understand whether a history of a prior shoulder arthroscopy is associated with adverse outcomes or complications after the index shoulder arthroplasty itself. METHODS: The Symphony Integrated DataVerse, an all-payer claims database, was used to identify patients undergoing primary shoulder arthroplasty (hemiarthroplasty, anatomic total shoulder arthroplasty, or reverse total shoulder arthroplasty) between 2017 to 2018. Current Procedural Terminology codes were used to identify patients who had undergone a shoulder arthroscopic procedure on the ipsilateral side within 2 years before the arthroplasty. Multivariate logistic regression analyses were used to assess whether prior shoulder arthroscopy was associated with higher risks of wound complications, postoperative stiffness, mechanical complications, prosthetic joint infection, revision surgery and readmissions within 90 days of the arthroplasty. RESULTS: In total, 19,429 patients were included, of which 837 (4.3%) had undergone shoulder arthroscopy within 2 years before the arthroplasty. Prior shoulder arthroscopy was associated with a significantly higher risk of prosthetic joint infection (odds ratio [OR] 2.74 [95% confidence interval {CI} 1.51-4.69]; P < .001) within 90 days of the arthroplasty. The greatest risk of prosthetic joint infection was associated with arthroscopies that took place within 3 months before the arthroplasty (OR 5.32 [95% CI 1.42-15.14]; P = .005). CONCLUSIONS: Undergoing an arthroscopic procedure of the ipsilateral shoulder before undergoing an arthroplasty was associated with greater risk of prosthetic joint infection. Furthermore, it appears that patients who received arthroscopy within the 3 months before arthroplasty had the highest risk of prosthetic joint infections. Physicians should not only anticipate possible inferior outcomes in patients who have had prior arthroscopy, but also consider delaying the arthroplasty by at least 3 months after the arthroscopy to mitigate the risks of experiencing this costly adverse event. LEVEL OF EVIDENCE: III.

Cost of Arthroscopic Rotator Cuff Repairs Is Primarily Driven by Procedure-Level Factors: A Single-Institution Analysis of an Ambulatory Surgery Center.

PURPOSE: To identify intraoperative drivers of cost associated with arthroscopic rotator cuff repairs (RCRs) through analysis of an institutional database. METHODS: This was a single-institution retrospective review of arthroscopic RCRs performed at an ambulatory surgical center between November 2016 and July 2019. Patient-level factors analyzed included age, sex, insurance type (private, Medicare, Medicaid, self-pay, and other government), American Society of Anesthesiologists grade (I, II, III, and missing), and Charlson comorbidity index (0, 1, 2, and ≥3). Procedure-level factors included use of biologics (decellularized dermal allograft or bioinductive healing implant), anesthesia type (regional block, monitored anesthesia care, or general), number of anchors and sutures, additional procedures (biceps tenodesis, distal clavicle resection, subacromial decompression), and operative time. Multivariate linear regression analysis was used to identify factors significantly associated with higher or lower charges. RESULTS: A total of 712 arthroscopic RCRs were included. The risk-adjusted operative charges were $19,728 (95% confidence interval $16,543 to $22,913). The above factors predicted nearly 65% of the variability in operative charges. The only patient-level factor significantly associated with lower charges was female sex (- $1,339; P = .002). Procedure-level factors significantly associated with higher charges were use of biologics (+ $17,791; P < .001), concurrent open biceps tenodesis (+ $4,027; P < .001), distal clavicle resection (+ $2,266; P = .039), use of regional block (+ $1,256; P = .004), number of anchors (+ $2,245/anchor; P < .001), and increasing operative time ($26/min). Other factors had no significant association. CONCLUSIONS: Procedural factors are the most significant drivers of operative cost in arthroscopic RCRs, such as quantity and type of implants; additional procedures such as biceps tenodesis and distal clavicle resection; and perioperative conditions such as type of anesthesia and total operating room time. Overall, patient-level factors were not shown to correlate well with operative costs, other than lower charges with female sex. LEVEL OF EVIDENCE: IV, economic study.

Patient Outcomes After Horizontal Cleavage Tear Repair: A Systematic Review.

PURPOSE: To analyze the clinical outcomes and survivorship of meniscal horizontal cleavage tear (HCT) repairs with hopes of guiding future treatment decisions. METHODS: Standard systematic review methodology was used. A comprehensive search of PubMed was conducted on June 1, 2019. The inclusion criteria were articles that were published in English, involved human subjects, and reported on at least 1 outcome after repair of HCTs. The exclusion criteria included technique guides and reviews, studies without full text available, and studies with HCT outcomes not separated from other repair groups. Effect heterogeneity was determined using the I2 measure. Forest plots were created in addition to a random-effects model to show the results. RESULTS: The systematic review yielded 19 studies evaluating 289 knees in a total of 273 patients. At most recent follow-up, there was a high probability of return to sport (93.1% [67 of 72]). Overall, 74% of patients (67 of 90) were symptom free at last follow-up, and 80% expressed satisfaction with their overall result (80 of 100). The most frequently reported subjective outcome was the Lysholm score, which improved from a preoperative study range of 48 to 79 (I2 = 20.7%, P = .283) to a postoperative study range of 56 to 99 (I2 = 49%, P = .081). The next most commonly reported was the International Knee Documentation Committee subjective score, which improved from a preoperative study range of 16 to 49 (I2 = 47.7%, P = .125) to a postoperative study range of 72 to 95 (I2 = 0%, P = .660). An overall 11.7% reported risk of reoperation was found, with most cases involving revision meniscectomy. Rates of complications beyond fixation failure were overall very low, with infrequent reports of septic arthritis and transitory dysesthesia. CONCLUSIONS: The short- to intermediate-term results of repair of HCTs are comparable to prior studies. Survivorship is comparable to repairs of other types of meniscal tears with high rates of return to sport and low complication rates. LEVEL OF EVIDENCE: Level IV, systematic review of Level I-IV studies.

Stable or seral? Fire-driven alternative states in aspen forests of western North America.

As important centres for biological diversity, aspen forests are essential to the function and aesthetics of montane ecosystems in western North America. Aspen stands are maintained by a nuanced relationship with wildfire, although in recent decades aspen mortality has increased. The need to understand the baseline environmental conditions that favour aspen is clear; however, long-term fire history reconstructions are rare due to the scarcity of natural archives in dry montane settings. Here, we analyse a high-resolution lake sediment record from southwestern, Utah, USA to quantify the compositional and burning conditions that promote stable (or seral) aspen forests. Our results show that aspen presence is negatively correlated with subalpine fir and that severe fires tend to promote persistent and diverse aspen ecosystems over centennial timescales. This information improves our understanding of aspen disturbance ecology and identifies the circumstances where critical transitions in montane forests may occur.

Rapidity of Correction of Hyponatremia Due to Syndrome of Inappropriate Secretion of Antidiuretic Hormone Following Tolvaptan.

BACKGROUND: Tolvaptan effectively corrects hyponatremia due to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), but undesired overcorrection can occur. We hypothesized that pretherapy parameters can predict the rapidity of response to tolvaptan in SIADH. STUDY DESIGN: Multicenter historical cohort study. SETTING & PARTICIPANTS: Adults with SIADH or congestive heart failure (CHF) treated with tolvaptan for a serum sodium concentration ≤ 130 mEq/L at 5 US hospitals. PREDICTORS: Demographic and laboratory parameters. OUTCOMES: Rate of change in serum sodium concentration. MEASUREMENTS: Spearman correlations, analysis of variance, and multivariable linear mixed-effects models. RESULTS: 28 patients with SIADH and 39 patients with CHF treated with tolvaptan (mean baseline serum sodium, 120.6 and 122.4 mEq/L, respectively) were studied. Correction of serum sodium concentration > 12 mEq/L/d occurred in 25% of patients with SIADH compared to 3% of those with CHF (P<0.001). Among patients with SIADH, the increase in serum sodium over 24 hours was correlated with baseline serum sodium concentration (r=-0.78; P<0.001), serum urea nitrogen concentration (SUN; r=-0.76; P<0.001), and estimated glomerular filtration rate (r=0.58; P=0.01). Baseline serum sodium and SUN concentrations were identified as independent predictors of change in serum sodium concentration in multivariable analyses. When patients were grouped into 4 categories according to baseline serum sodium and SUN median values, those with both low baseline serum sodium (≤121 mEq/L) and low baseline SUN concentrations (≤10mg/dL) exhibited a significantly greater rate of increase in serum sodium concentration (mean 24-hour increase of 15.4 mEq/L) than the other 3 categories (P<0.05). Among patients with CHF, only baseline SUN concentration was identified as an independent predictor of change in serum sodium concentration over time. LIMITATIONS: Lack of uniformity in serial serum sodium concentration determinations and documentation of water intake. CONCLUSIONS: Baseline serum sodium and SUN values are predictive of the rapidity of hyponatremia correction following tolvaptan use in SIADH. We advise caution when dosing tolvaptan in patients with both low serum sodium and SUN concentrations.

Forkhead factor FoxO1 is essential for placental morphogenesis in the developing embryo.

Forkhead box O1 (FoxO1), a member of the Forkhead box-containing O family of transcription factors, is a key regulator of numerous genes that govern a wide array of cellular functions, including differentiation, homeostasis, and survival. However, the role of FoxO1 in development remains elusive. Here, we describe an essential and previously undefined role for FoxO1 in placental development. We demonstrate that FoxO1-null embryos up to embryonic day 9.0 (E9.0) are indistinguishable, including their morphology, cardiovascular structure, and vascular gene expression, from wild-type (WT) littermates. However, FoxO1-nulls manifested a profoundly swollen/hydropic allantois, which failed to fuse with the chorion, a phenotype that leads to subsequent cardiovascular malformation, progressive apoptotic cell death, and embryonic lethality at E10.5. Quantitative RT-PCR analysis of genes involved in placental development revealed significant attenuation of VCAM1 expression in FoxO1-null embryos. Using immunohistochemical, transcriptional, and chromatin immunoprecipitation assays, we further discovered that FoxO1 is an essential upstream regulator of the VCAM1 gene. Collectively, our findings provide critical molecular insight into a unique FoxO1-VCAM1 axis that governs placental morphogenesis, a process that is essential for subsequent normal cardiovascular development and fetal life.

Responding to avian influenza A H5N1 detection on a hospital property in Maine-An interdisciplinary approach.

BACKGROUND: The risk of infection with avian influenza A viruses currently circulating in wild and domestic birds in the Americas is considered low for the general public; however, detections in humans have been reported and warning signs of increased zoonotic potential have been identified. In December 2022, two Canada geese residing on the grounds of an urban hospital in Maine tested positive for influenza A H5N1 clade 2.3.4.4b. AIMS: Given the opportunity for exposure to staff and hospital visitors through potentially infected faeces on the property, public health authorities determined mitigation efforts were needed to prevent the spread of disease. The ensuing response relied on collaboration between the public health and animal health agencies to guide the hospital through efforts in preventing possible zoonotic transmission to humans. MATERIALS AND METHODS: Mitigation efforts included staff communication and education, environmental cleaning and disinfection, enhanced illness surveillance among staff and patients, and exposure and source reduction. RESULTS: No human H5N1 cases were identified, and no additional detections in birds on the property occurred. Hospital staff identified barriers to preparedness resulting from a lack of understanding of avian influenza A viruses and transmission prevention methods, including avian influenza risk in resident wild bird populations and proper wildlife management methods. CONCLUSION: As this virus continues to circulate at the animal-human interface, this event and resulting response highlights the need for influenza A H5N1 risk awareness and guidance for facilities and groups not traditionally involved in avian influenza responses.

Mosaic of Somatic Mutations in Earth's Oldest Living Organism, Pando.

Understanding how mutations arise and spread through individuals and populations is fundamental to evolutionary biology. Most organisms have a life cycle with unicellular bottlenecks during reproduction. However, some organisms like plants, fungi, or colonial animals can grow indefinitely, changing the manner in which mutations spread throughout both the individual and the population. Furthermore, clonally reproducing organisms may also achieve exceedingly long lifespans, making somatic mutation an important mechanism of creating heritable variation for Darwinian evolution by natural selection. Yet, little is known about intra-organism mutation rates and evolutionary trajectories in long-lived species. Here, we study the Pando aspen clone, the largest known quaking aspen ( Populus tremuloides ) clone founded by a single seedling and thought to be one of the oldest studied organisms. Aspen reproduce vegetatively via new root-borne stems forming clonal patches, sometimes spanning several hectares. To study the evolutionary history of the Pando clone, we collected and sequenced over 500 samples from Pando and neighboring clones, as well as from various tissue types within Pando, including leaves, roots, and bark. We applied a series of filters to distinguish somatic mutations from the pool of both somatic and germline mutations, incorporating a technical replicate sequencing approach to account for uncertainty in somatic mutation detection. Despite root spreading being spatially constrained, we observed only a modest positive correlation between genetic and spatial distance, suggesting the presence of a mechanism preventing the accumulation and spread of mutations across units. Phylogenetic models estimate the age of the clone to between ~16,000-80,000 years. This age is generally corroborated by the near-continuous presence of aspen pollen in a lake sediment record collected from Fish Lake near Pando. Overall, this work enhances understanding of mutation accumulation and dispersal within and between ramets of long-lived, clonally-reproducing organisms. Significance Statement: This study enhances our understanding of evolutionary processes in long-lived clonal organisms by investigating somatic mutation accumulation and dispersal patterns within the iconic Pando aspen clone. The authors estimated the clone to be between 10,000 and 80,000 years old and uncovered a modest spatial genetic structure in the 42.6-hectare clone, suggesting localized mutation build-up rather than dispersal along tissue lineages. This work sheds light on an ancient organism and how plants may evolve to preserve genetic integrity in meristems fueling indefinite growth, with implications for our comprehension of adaptive strategies in long-lived perennials.

Modalities for teaching responsible and ethical conduct of research online: Lessons learned from an undergraduate workshop in Utah.

The COVID-19 pandemic disrupted scientific research, teaching, and learning in higher education and forced many institutions to explore new modalities in response to the abrupt shift to remote learning. Accordingly, many colleges and universities struggled to provide the training, technology, and best practices to support faculty and students, especially those at historically disadvantaged and underrepresented institutions. In this study we investigate different remote learning modalities to improve and enhance research education training for faculty and students. We specifically focus on Responsible and Ethical Conduct of Research (RECR) and research mentoring content to help address the newly established requirements of the National Science Foundation for investigators. To address this need we conducted a workshop to determine the effectiveness of three common research education modalities: Live Lecture, Podcast, and Reading. The Live Lecture sessions provided the most evidence of learning based on the comparison between pre- and post-test results, whereas the Podcast format was well received but produced a slight (and non-significant) decline in scores between the pre- and post-tests. The Reading format showed no significant improvement in learning. The results of our workshop illuminate the effectiveness and obstacles associated with various remote learning modalities, enabling us to pinpoint areas that require additional refinement and effort, including the addition of interactive media in Reading materials.

Laryngeal aging and acoustic changes in male rat ultrasonic vocalizations.

This study examined changes in the acoustic and temporal structure of ultrasonic vocalizations as a function of age and correlated acoustic changes with vocal fold microstructure. Ultrasonic vocalizations were recorded in three age groups of male rats: aged (24-26 months), middle-aged (17-18 months), and young (4-5 months). Acoustic and structural changes in vocal fold tissue were evident by 18 months of age. Histological analyses revealed decreased density of elastin and hyaluronic acid and increased collagen density in the middle-aged and aged groups compared to the young rats. Laryngeal microstructure correlated with some of the ultrasonic acoustic features. These results show that male Long Evans rats experience changes in ultrasonic acoustic structure by middle age, and these changes correlate with deterioration in laryngeal microstructure. Ultrasonic vocalizations can be used as a model system for age-related degeneration in vocal fold structure and function.

Nkx2-5 transactivates the Ets-related protein 71 gene and specifies an endothelial/endocardial fate in the developing embryo.

Recent studies support the existence of a common progenitor for the cardiac and endothelial cell lineages, but the underlying transcriptional networks responsible for specification of these cell fates remain unclear. Here we demonstrated that Ets-related protein 71 (Etsrp71), a newly discovered ETS family transcription factor, was a novel downstream target of the homeodomain protein, Nkx2-5. Using genetic mouse models and molecular biological techniques, we demonstrated that Nkx2-5 binds to an evolutionarily conserved Nkx2-5 response element in the Etsrp71 promoter and induces the Etsrp71 gene expression in vitro and in vivo. Etsrp71 was transiently expressed in the endocardium/endothelium of the developing embryo (E7.75-E9.5) and was extinguished during the latter stages of development. Using a gene disruption strategy, we found that Etsrp71 mutant embryos lacked endocardial/endothelial lineages and were nonviable. Moreover, using transgenic technologies and transcriptional and chromatin immunoprecipitation (ChIP) assays, we further established that Tie2 is a direct downstream target of Etsrp71. Collectively, our results uncover a novel functional role for Nkx2-5 and define a transcriptional network that specifies an endocardial/endothelial fate in the developing heart and embryo.

Nerve Injuries with the Direct Anterior Approach to Total Hip Arthroplasty.

* While no single approach for total hip arthroplasty (THA) has been proven to be superior to others in terms of patient outcomes, the direct anterior approach (DAA) is becoming increasingly popular. * All of the described techniques for THA carry a small risk of nerve injury. * Identifying risk factors for nerve injury and mitigating these risks where feasible are imperative in order to reduce the incidence of this complication with any approach for THA.

Outcome reporting patterns in total knee arthroplasty: A systematic review.

BACKGROUND: Total knee arthroplasty (TKA) is one of the most effective ways to treat end-stage painful conditions of the knee. However, non-standardized reporting patterns can make quantitative analysis of patient outcomes difficult. METHODS: A systematic review of the literature was performed using keywords "total knee arthroplasty" and "total knee replacement." Randomized controlled trials (RCTs) meeting the inclusion criteria were sorted and reviewed. Type of study, outcome measures used to report their results, and the actual results were recorded. Quantitative analysis was performed. RESULTS: A total of 233 RCTs were included. There was significant variability in the reporting of short term and long term outcomes in total knee arthroplasty. The most common treatment domains in order of decreasing frequency were objective knee function, subjective knee function, perioperative complications, and pain. Range of motion was the most common outcome metric reported in all the RCTs and also was the most common metric used to assess objective knee function. The most common patient reported outcome measure used to assess postoperative function was the Knee Society Score followed by Knee Injury and Osteoarthritis Outcome Score. The Visual Analog Scale was the most common measurement tool used to assess postoperative pain. Most studies assessed patient outcomes in three treatment domains. None reported outcomes in all seven domains. CONCLUSION: There is significant variability in outcome reporting patterns in TKA literature. Most studies do not track outcomes comprehensively, with a significant minority of the RCTs tracking outcomes in only one treatment domain.

Outcome Reporting Patterns in Total Hip Arthroplasty: A Systematic Review of Randomized Clinical Trials.

BACKGROUND: There has been a shift toward using patient-reported outcome measures (PROMs) to capture functional improvement and patient satisfaction after total hip arthroplasty (THA). Because there is no standard measure or set of measures, variability in reporting patterns makes comparison across studies difficult. METHODS: We performed a review of the literature using the keywords "total hip arthroplasty" and "total hip replacement" to electronically search PubMed, using the date range August 1, 2014, to August 1, 2019. Randomized clinical trials (RCTs) that were published in 12 high-impact journals were analyzed. RESULTS: One hundred and fifty-nine RCTs were included. The most common topic of investigation was hip implant design and materials, followed by the effect of different hip approaches on patient outcomes. The follow-up period was classified as short-term (<2 years), mid-term (2 to 10 years), or long-term (>10 years). Only 6% of the RCTs reported long-term outcomes. The comprehensiveness of studies was determined on the basis of how many of the 7 following outcome domains were assessed: subjective hip function (PROMs), objective outcome measures (examination findings, laboratory values, etc.), imaging analysis, survivorship, patient satisfaction, pain assessment, and postoperative complications. Subjective hip function and imaging findings were the most commonly reported outcome domains, while implant survivorship and patient satisfaction were the least frequently reported. There was substantial variation in outcome reporting, with 35 unique PROMs utilized to assess subjective hip function. Although the Harris hip score was the most commonly used joint-specific PROM, it was only reported in 42% of the studies. None of the RCTs reported results in all 7 outcome domains, and 13.8% of studies reported results in only 1 outcome domain. CONCLUSIONS: There is substantial variability and a lack of comprehensiveness in outcome measures used to report results in THA clinical trials, making it nearly impossible to perform cross-study comparisons. CLINICAL RELEVANCE: There is an immediate need for the establishment of a standardized set of measures to allow comparison of outcomes across studies.

Selenium bioaccumulation in fish exposed to coal ash at the Tennessee Valley Authority Kingston spill site.

In December 2008, 4.1 million cubic meters of coal ash were released into the Emory and Clinch Rivers by the Tennessee Valley Authority Kingston Fossil Plant. Coal ash contains several contaminants, including the bioaccumulative metalloid selenium (Se). Because Se is predominantly accumulated in aquatic organisms through dietary rather than aqueous exposure, tissue-based toxicity thresholds for Se are currently being considered. The proposed threshold concentrations range between 4 µg/g and 9 µg/g Se (dry wt.) in whole body fish, with a proposed fillet threshold of 11.8 µg/g. In the present study, the authors examined the spatial and temporal trends in Se bioaccumulation and examined the relationship between the Se content in fillets and in whole bodies of fish collected around the Kingston spill site to determine whether Se bioaccumulation was a significant concern at the ash spill site. Whereas Se concentrations in fish (whole bodies and fillets) were elevated at sampling locations affected by the Kingston ash spill relative to reference locations, concentrations do not appear to be above risk thresholds and have not been increasing over the 5-yr period since the spill. These findings are not only relevant to guiding the human health and ecological risk assessments at the Kingston ash spill site, but because of current national discussions on appropriate guidelines for Se in fish as well for the disposal of coal combustion wastes, the results are also relevant to the general understanding of Se bioaccumulation in contaminated water bodies.

Hand2 controls osteoblast differentiation in the branchial arch by inhibiting DNA binding of Runx2.

Members of the basic helix-loop-helix (bHLH) family of transcription factors regulate the specification and differentiation of numerous cell types during embryonic development. Hand1 and Hand2 are expressed by a subset of neural crest cells in the anterior branchial arches and are involved in craniofacial development. However, the precise mechanisms by which Hand proteins mediate biological actions and regulate downstream target genes in branchial arches is largely unknown. Here, we report that Hand2 negatively regulates intramembranous ossification of the mandible by directly inhibiting the transcription factor Runx2, a master regulator of osteoblast differentiation. Hand proteins physically interact with Runx2, suppressing its DNA binding and transcriptional activity. This interaction is mediated by the N-terminal domain of the Hand protein and requires neither dimerization with other bHLH proteins nor DNA binding. We observed partial colocalization of Hand2 and Runx2 in the mandibular primordium of the branchial arch, and downregulation of Hand2 precedes Runx2-driven osteoblast differentiation. Hand2 hypomorphic mutant mice display insufficient mineralization and ectopic bone formation in the mandible due to accelerated osteoblast differentiation, which is associated with the upregulation and ectopic expression of Runx2 in the mandibular arch. Here, we show that Hand2 acts as a novel inhibitor of the Runx2-DNA interaction and thereby regulates osteoblast differentiation in branchial arch development.