Fact or fiction: the "5 mm Rule" in greater tuberosity fractures of the proximal humerus.

PURPOSE: The purposes of this study were 1) to assess the outcome of nonoperative management of GT fractures with > 5 mm of displacement and 2) to assess whether there is a correlation between degree of displacement and outcome. METHODS: This study was a retrospective review of consecutive low-energy GT fractures from 2011 to 2020. Radiographs from all visits were reviewed. The direction of maximal displacement was assessed. Subjects were stratified based on the amount of maximal displacement: Group 1: 0-5 mm, Group 2: 5-10 mm, Group 3: > 10 mm. Range of motion (ROM) at the time of final follow-up was assessed. The presence of persistent shoulder pain after healing was noted, as well as whether supplemental subacromial corticosteroid injection was provided as part of long-term treatment. RESULTS: A cohort of 93 fractures comprised the study group. Mean age was 62 years. Mean follow-up was 20 months. All fractures went on to union. Mean displacement was 6.2 mm. There were 43 patients in Group 1, 43 in Group 2, and 7 in Group 3. Maximal displacement was most commonly inferolateral or lateral, accounting for a combined 77% of all patients. There was no difference in final ROM between displacement groups, with at least 155 degrees of forward elevation and 45 degrees of ER in all three groups. There was no difference between Group 1 and Groups 2/3 in frequency of persistent pain or likelihood of receiving a steroid injection. CONCLUSION: Our findings do not support a discrete 5 mm displacement threshold for surgical repair of isolated greater tuberosity fractures.

Specific Factors Affecting Operating Room Efficiency: An Analysis of Case Time Estimates.

PURPOSE: Operating room (OR) efficiency has an impact on surgeon productivity and patient experience. Accuracy of case duration estimation is important to optimize OR efficiency. The purpose of this study was to identify factors associated with inaccurate case time estimates in outpatient hand surgery. A better understanding of these findings may help to improve OR efficiency and scheduling. METHODS: All outpatient hand surgical cases from 2018 to 2019 were reviewed. Poorly-estimated cases (i.e., poor scheduling accuracy) were defined as those cases where the actual operative time differed from the predicted time by >50% (either quicker by >50% or slower by >50% than the predicted time). The percentages of poorly-estimated cases were analyzed, categorized, and compared by surgeon, procedure type, and scheduled case length. RESULTS: A total of 6,620 cases were identified. Of 1,107 (16.7%) cases with poorly estimated case durations, 75.2% were underestimated. There was no difference in the likelihood of poor estimation related to start time. Well-estimated cases tended to have longer scheduled case duration, but shorter realized case duration and surgical time. Our systems analysis identified specific surgeons and procedures as predictable outliers. Cases scheduled for 15-30 minutes frequently were inaccurate, whereas cases scheduled for 30-45 and 106-120 minutes had accurate estimates. CONCLUSIONS: The accuracy of case time estimations in a standard outpatient hand surgery practice is highly variable. Nearly one-fifth of outpatient hand surgery case durations are poorly estimated, and inaccurate case time estimation can be predicted based on surgeon, procedure type, and case time. CLINICAL RELEVANCE: Maximizing OR efficiency should be a priority for surgeons and hospital systems. With multiple surgeries done per day, the efficiency of the OR has an impact on surgeon productivity and patient experience.

Proximal Hamate Autograft for Proximal Scaphoid Pole Reconstruction A Case Report.

Avascular necrosis (AVN) and subsequent fragmentation of the proximal pole of the scaphoid following fracture is a challenging problem to treat. Multiple treatment methods have been described, although they have been shown to have varying degrees of success and are associated with donor site morbidities. This case report demonstrates a technique and the excellent radiographic and clinical outcome at 8 months postoperatively for reconstruction of the proximal pole of the scaphoid using an ipsilateral proximal pole of the hamate autograft.

Targeted Muscle Reinnervation (TMR) and Other Considerations in Upper Extremity Amputation.

Targeted muscle reinnervation (TMR) is a procedure in which amputated nerves are transferred to motor branches of functionally expendable muscles, which can then serve as "biological amplifiers" of neurologic information. It is a technique that was developed with the primary intent of improving myoelectric prosthesis control in high level upper extremity amputees. Over time, TMR has been shown to confer significant benefits in terms of both residual and phantom limb pain and as such has become a powerful tool in neuroma management in amputees and non-amputees. This review first discusses general principles of amputation management in the upper extremity, including the different types of prosthetics that are available for these patients. The history, rationale, and evolution of TMR will then be outlined, followed by several relevant surgical principles. Finally, the current evidence for and against TMR will be reviewed. Robust data on the functional benefits are still needed, and future studies will continue to clarify its role in both upper and lower extremity amputees.

Foxd3 controls heterochromatin-mediated repression of repeat elements and 2-cell state transcription.

Repeat element transcription plays a vital role in early embryonic development. The expression of repeats such as MERVL characterises mouse embryos at the 2-cell stage and defines a 2-cell-like cell (2CLC) population in a mouse embryonic stem cell culture. Repeat element sequences contain binding sites for numerous transcription factors. We identify the forkhead domain transcription factor FOXD3 as a regulator of major satellite repeats and MERVL transcription in mouse embryonic stem cells. FOXD3 binds to and recruits the histone methyltransferase SUV39H1 to MERVL and major satellite repeats, consequentially repressing the transcription of these repeats by the establishment of the H3K9me3 heterochromatin modification. Notably, depletion of FOXD3 leads to the de-repression of MERVL and major satellite repeats as well as a subset of genes expressed in the 2-cell state, shifting the balance between the stem cell and 2-cell-like population in culture. Thus, FOXD3 acts as a negative regulator of repeat transcription, ascribing a novel function to this transcription factor.

Complete loss of H3K9 methylation dissolves mouse heterochromatin organization.

Histone H3 lysine 9 (H3K9) methylation is a central epigenetic modification that defines heterochromatin from unicellular to multicellular organisms. In mammalian cells, H3K9 methylation can be catalyzed by at least six distinct SET domain enzymes: Suv39h1/Suv39h2, Eset1/Eset2 and G9a/Glp. We used mouse embryonic fibroblasts (MEFs) with a conditional mutation for Eset1 and introduced progressive deletions for the other SET domain genes by CRISPR/Cas9 technology. Compound mutant MEFs for all six SET domain lysine methyltransferase (KMT) genes lack all H3K9 methylation states, derepress nearly all families of repeat elements and display genomic instabilities. Strikingly, the 6KO H3K9 KMT MEF cells no longer maintain heterochromatin organization and have lost electron-dense heterochromatin. This is a compelling analysis of H3K9 methylation-deficient mammalian chromatin and reveals a definitive function for H3K9 methylation in protecting heterochromatin organization and genome integrity.

Clinical photographs in the assessment of adult spinal deformity: a comparison to radiographic parameters.

OBJECTIVE: The goal of this study was to reliably predict sagittal and coronal spinal alignment with clinical photographs by using markers placed at easily localized anatomical landmarks. METHODS: A consecutive series of patients with adult spinal deformity were enrolled from a single center. Full-length standing radiographs were obtained at the baseline visit. Clinical photographs were taken with reflective markers placed overlying C2, S1, the greater trochanter, and each posterior-superior iliac spine. Sagittal radiographic parameters were C2 pelvic angle (CPA), T1 pelvic angle (TPA), and pelvic tilt. Coronal radiographic parameters were pelvic obliquity and T1 coronal tilt. Linear regressions were performed to evaluate the relationship between radiographic parameters and their photographic "equivalents." The data were reanalyzed after stratifying the cohort into low-body mass index (BMI) (< 30) and high-BMI (≥ 30) groups. Interobserver and intraobserver reliability was assessed for clinical measures via intraclass correlation coefficients (ICCs). RESULTS: A total of 38 patients were enrolled (mean age 61 years, mean BMI 27.4 kg/m2, 63% female). All regression models were significant, but sagittal parameters were more closely correlated to photographic parameters than coronal measurements. TPA and CPA had the strongest associations with their photographic equivalents (both r2 = 0.59, p < 0.001). Radiographic and clinical parameters tended to be more strongly correlated in the low-BMI group. Clinical measures of TPA and CPA had high intraobserver reliability (all ICC > 0.99, p < 0.001) and interobserver reliability (both ICC > 0.99, p < 0.001). CONCLUSIONS: The photographic measures of spinal deformity developed in this study were highly correlated with their radiographic counterparts and had high inter- and intraobserver reliability. Clinical photography can not only reduce radiation exposure in patients with adult spinal deformity, but also be used to assess deformity when full-spine radiographs are unavailable.

Regional anesthesia for clavicle fracture surgery is safe and effective.

BACKGROUND: Historically, clavicle fracture repairs have been performed with patients under general anesthesia. However, in the past few years, the combination of an interscalene brachial plexus block and a modified superficial cervical plexus block has been described to provide adequate anesthesia for clavicle fracture surgery, with the added benefit of postoperative analgesia. In March 2013, members of our anesthesiology department began using this block with sedation for a subset of patients undergoing clavicle fracture fixation. METHODS: This study was a retrospective review of patients who underwent clavicle fracture repair at a single institution between June 2014 and November 2017. The decision on the type of anesthesia (regional vs. general) was made jointly by the patient, anesthesiologist, and surgeon. Demographic data, relevant perioperative times, and intraoperative pain medication consumption were recorded, and comparisons of these variables were made between the regional and general anesthesia groups. RESULTS: A total of 110 patients with 110 fractures were included. Of these patients, 52 received only regional anesthesia with the combined block whereas 58 received general anesthesia with an interscalene brachial plexus block. No major anesthetic-related complications were noted in any patients, and there were no cases in which regional anesthesia had to be converted to general anesthesia because of block failure. The anesthesia start time was significantly longer in the general anesthesia group (29 minutes vs. 20 minutes, P = .022), as was the total case time (164 minutes vs. 131 minutes, P < .001). Patients in the general anesthesia group required significantly more intraoperative fentanyl to be administered (207 µg vs. 141 µg, P = .002). CONCLUSION: Regional anesthesia using a combined brachial plexus and modified superficial cervical plexus block is a reliable, efficacious technique. The combined block appears to be a reasonable alternative to general anesthesia with an interscalene brachial plexus block, and it may have benefits regarding the anesthesia start time and total case time.

Surgical Site Infection After Open Upper Extremity Fracture and the Effect of Urgent Operative Intervention.

OBJECTIVES: To identify which factors are predictive of surgical site infection in upper extremity fractures, and to assess whether the timing of operative debridement influences infection risk. DESIGN: Retrospective database review. SETTING: Hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database. PATIENTS: Patients in the NSQIP database with fractures involving the upper extremity. INTERVENTION: Surgical management of upper extremity fracture, including operative debridement for open injuries. MAIN OUTCOME MEASUREMENTS: Surgical site infection, including both superficial and deep infections. RESULTS: A total of 22,578 patients were identified, including 1298 patients with open injuries (5.7% of total). The overall wound infection rate was 0.79%. Patients with open injuries were found to have a higher incidence of infection compared with those with closed injuries (1.7% vs. 0.7%, P < 0.001). Independent risk factors for 30-day infection included open fracture diagnosis, obesity, smoking, and American Society of Anesthesiolgists class >2 (all P < 0.05). Of patients with open fractures, 79.7% were taken expediently to the operating room. The rate of infection did not differ based on whether surgery was performed expediently or not (1.8% vs. 1.1%, P = 0.431). CONCLUSIONS: Based on an analysis of the NSQIP database, the overall risk of surgical site infection following intervention for open or closed upper extremity fractures remains low. Risk factors for infection include open injury, obesity, and cigarette smoking. There was no difference in the infection rate based on the urgency of operative debridement. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Surgical Management of Scaphotrapeziotrapezoid Arthritis.

Scaphotrapeziotrapezoid (STT) arthritis occurs commonly with basal joint arthritis, but can also occur in isolation or in conjunction with other patterns of wrist arthritis, such as scapholunate advanced collapse. Surgical options depend on the specific clinical scenario encountered. Isolated STT arthritis was classically managed with arthrodesis, but is now often addressed with distal scaphoid resection (open or arthroscopic), trapeziectomy (partial or complete) and partial trapezoid resection, or implant arthroplasty. Development of postoperative dorsal intercalary segment instability is a notable concern with any of these techniques. STT arthritis in conjunction with basal joint arthritis can be managed effectively with trapeziectomy and either partial trapezoid excision or distal scaphoid excision. STT arthritis with scapholunate advanced collapse is uncommon, but can be managed with proximal row carpectomy or scaphoidectomy and four-corner fusion. If basal joint arthritis is also present, trapeziectomy can additionally be performed, but grip strength is likely to be substantially diminished.

snakePipes: facilitating flexible, scalable and integrative epigenomic analysis.

SUMMARY: Due to the rapidly increasing scale and diversity of epigenomic data, modular and scalable analysis workflows are of wide interest. Here we present snakePipes, a workflow package for processing and downstream analysis of data from common epigenomic assays: ChIP-seq, RNA-seq, Bisulfite-seq, ATAC-seq, Hi-C and single-cell RNA-seq. snakePipes enables users to assemble variants of each workflow and to easily install and upgrade the underlying tools, via its simple command-line wrappers and yaml files. AVAILABILITY AND IMPLEMENTATION: snakePipes can be installed via conda: `conda install -c mpi-ie -c bioconda -c conda-forge snakePipes'. Source code (https://github.com/maxplanck-ie/snakepipes) and documentation (https://snakepipes.readthedocs.io/en/latest/) are available online. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

RELACS nuclei barcoding enables high-throughput ChIP-seq.

Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) is an invaluable tool for mapping chromatin-associated proteins. Current barcoding strategies aim to improve assay throughput and scalability but intense sample handling and lack of standardization over cell types, cell numbers and epitopes hinder wide-spread use in the field. Here, we present a barcoding method to enable high-throughput ChIP-seq using common molecular biology techniques. The method, called RELACS (restriction enzyme-based labeling of chromatin in situ) relies on standardized nuclei extraction from any source and employs chromatin cutting and barcoding within intact nuclei. Barcoded nuclei are pooled and processed within the same ChIP reaction, for maximal comparability and workload reduction. The innovative barcoding concept is particularly user-friendly and suitable for implementation to standardized large-scale clinical studies and scarce samples. Aiming to maximize universality and scalability, RELACS can generate ChIP-seq libraries for transcription factors and histone modifications from hundreds of samples within three days.

Community-Driven Data Analysis Training for Biology.

The primary problem with the explosion of biomedical datasets is not the data, not computational resources, and not the required storage space, but the general lack of trained and skilled researchers to manipulate and analyze these data. Eliminating this problem requires development of comprehensive educational resources. Here we present a community-driven framework that enables modern, interactive teaching of data analytics in life sciences and facilitates the development of training materials. The key feature of our system is that it is not a static but a continuously improved collection of tutorials. By coupling tutorials with a web-based analysis framework, biomedical researchers can learn by performing computation themselves through a web browser without the need to install software or search for example datasets. Our ultimate goal is to expand the breadth of training materials to include fundamental statistical and data science topics and to precipitate a complete re-engineering of undergraduate and graduate curricula in life sciences. This project is accessible at https://training.galaxyproject.org.

Epigenetic alterations in longevity regulators, reduced life span, and exacerbated aging-related pathology in old father offspring mice.

Advanced age is not only a major risk factor for a range of disorders within an aging individual but may also enhance susceptibility for disease in the next generation. In humans, advanced paternal age has been associated with increased risk for a number of diseases. Experiments in rodent models have provided initial evidence that paternal age can influence behavioral traits in offspring animals, but the overall scope and extent of paternal age effects on health and disease across the life span remain underexplored. Here, we report that old father offspring mice showed a reduced life span and an exacerbated development of aging traits compared with young father offspring mice. Genome-wide epigenetic analyses of sperm from aging males and old father offspring tissue identified differentially methylated promoters, enriched for genes involved in the regulation of evolutionarily conserved longevity pathways. Gene expression analyses, biochemical experiments, and functional studies revealed evidence for an overactive mTORC1 signaling pathway in old father offspring mice. Pharmacological mTOR inhibition during the course of normal aging ameliorated many of the aging traits that were exacerbated in old father offspring mice. These findings raise the possibility that inherited alterations in longevity pathways contribute to intergenerational effects of aging in old father offspring mice.

Every-other-day feeding extends lifespan but fails to delay many symptoms of aging in mice.

Dietary restriction regimes extend lifespan in various animal models. Here we show that longevity in male C57BL/6J mice subjected to every-other-day feeding is associated with a delayed onset of neoplastic disease that naturally limits lifespan in these animals. We compare more than 200 phenotypes in over 20 tissues in aged animals fed with a lifelong every-other-day feeding or ad libitum access to food diet to determine whether molecular, cellular, physiological and histopathological aging features develop more slowly in every-other-day feeding mice than in controls. We also analyze the effects of every-other-day feeding on young mice on shorter-term every-other-day feeding or ad libitum to account for possible aging-independent restriction effects. Our large-scale analysis reveals overall only limited evidence for a retardation of the aging rate in every-other-day feeding mice. The data indicate that every-other-day feeding-induced longevity is sufficiently explained by delays in life-limiting neoplastic disorders and is not associated with a more general slowing of the aging process in mice.Dietary restriction can extend the life of various model organisms. Here, Xie et al. show that intermittent periods of fasting achieved through every-other-day feeding protect mice against neoplastic disease but do not broadly delay organismal aging in animals.

High-dose maternal folic acid supplementation before conception impairs reversal learning in offspring mice.

Maternal folic acid (FA) supplementation prior to and during gestation is recommended for the prevention of neural tube closure defects in the developing embryo. Prior studies, however, suggested that excessive FA supplementation during gestation can be associated with toxic effects on the developing organism. Here, we address whether maternal dietary folic acid supplementation at 40 mg/kg chow (FD), restricted to a period prior to conception, affects neurobehavioural development in the offspring generation. Detailed behavioural analyses showed reversal learning impairments in the Morris water maze in offspring derived from dams exposed to FD prior to conceiving. Furthermore, offspring of FD dams showed minor and transient gene expression differences relative to controls. Our data suggest that temporary exposure of female germ cells to FD is sufficient to cause impaired cognitive flexibility in the subsequent generation.

deepTools2: a next generation web server for deep-sequencing data analysis.

We present an update to our Galaxy-based web server for processing and visualizing deeply sequenced data. Its core tool set, deepTools, allows users to perform complete bioinformatic workflows ranging from quality controls and normalizations of aligned reads to integrative analyses, including clustering and visualization approaches. Since we first described our deepTools Galaxy server in 2014, we have implemented new solutions for many requests from the community and our users. Here, we introduce significant enhancements and new tools to further improve data visualization and interpretation. deepTools continue to be open to all users and freely available as a web service at deeptools.ie-freiburg.mpg.de The new deepTools2 suite can be easily deployed within any Galaxy framework via the toolshed repository, and we also provide source code for command line usage under Linux and Mac OS X. A public and documented API for access to deepTools functionality is also available.

Developing the Total Disability Index Based on an Analysis of the Interrelationships and Limitations of Oswestry and Neck Disability Index.

STUDY DESIGN: Retrospective. OBJECTIVE: This study assessed the feasibility of combining Oswestry and Neck Disability Index (ODI and NDI) into 1 shorter "Total Disability Index" (TDI) from which reconstructed scores could be computed. SUMMARY OF BACKGROUND DATA: ODI and NDI are not pure assessments of disability related to back and neck, respectively. Because of similarities/redundancies of questions, ODI scores may be elevated in neck-pain patients and the converse is true for NDI in back-pain patients. METHODS: Spine patients completed ODI and NDI, and complaints were recorded as back pain (BP), neck pain (NP), or both (BNP). Questionnaire scores were compared across cohorts via descriptives and Spearman (ρ) correlations. In exploring the feasibility of merging ODI/NDI, TDI was constructed from 9 ODI and 5 NDI items. Extracting questions from TDI, reconstructed 9-item rODI and 10-item rNDI indices were formed and compared with true ODI/NDI. RESULTS: There were a total of 1207 patients: 741 BP, 134 NP, and 268 BNP. Mean ODI was 37 ±â€Š21 and mean NDI was 32 ±â€Š21. Patients with concurrent BP and NP had significantly more disability. Seventy-eight patients of 134 (58%) patients with NP only had at least "moderate disability" by ODI and 297 of 741 (40%) patients with back pain only, had at least "moderate disability" by NDI. ODI versus NDI correlation was ρ = 0.755; ODI versus reconstructed rODI correlated at ρ = 0.985, and NDI versus reconstructed rNDI correlated at ρ = 0.967 (P < 0.01). CONCLUSION: Elevated ODI/NDI scores in patients with isolated complaints show that disability in 1 region affects scores on both surveys. This study constructed a 14-item TDI that represents every domain of ODI/NDI with exception of ODI "Sex Life." From this TDI, reconstructed scores correlated near perfectly with true scores. TDI provides a more global assessment of spinal disability and is a questionnaire that reduces the time burden to patients. The TDI allows for simultaneous assessment of back, neck, and global spinal disability.

Everything Achilles: Knowledge Update and Current Concepts in Management: AAOS Exhibit Selection.

Achilles tendon pathology is common and affects athletes and nonathletes alike. The cause is multifactorial and controversial, involving biological, anatomical, and mechanical factors. A variety of conditions characterized by Achilles tendon inflammation and/or degeneration can be clinically and histologically differentiated. These include insertional Achilles tendinopathy, retrocalcaneal bursitis, Achilles paratenonitis, Achilles tendinosis, and Achilles paratenonitis with tendinosis. The mainstay of treatment for all of these diagnoses is nonoperative. There is a large body of evidence addressing treatment of acute and chronic Achilles tendon ruptures; however, controversy remains.

Limited effects of an eIF2αS51A allele on neurological impairments in the 5xFAD mouse model of Alzheimer's disease.

Alzheimer's disease (AD) has been associated with increased phosphorylation of the translation initiation factor 2α (eIF2α) at serine 51. Increased phosphorylation of eIF2α alters translational control and may thereby have adverse effects on synaptic plasticity, learning, and memory. To analyze if increased levels of p-eIF2α indeed promote AD-related neurocognitive impairments, we crossed 5xFAD transgenic mice with an eIF2α(S51A) knock-in line that expresses the nonphosphorylatable eIF2α variant eIF2α(S51A). Behavioral assessment of the resulting mice revealed motor and cognitive deficits in 5xFAD mice that were, with the possible exception of locomotor hyperactivity, not restored by the eIF2α(S51A) allele. Telemetric intracranial EEG recordings revealed no measurable effects of the eIF2α(S51A) allele on 5xFAD-associated epileptic activity. Microarray-based transcriptome analyses showed clear transcriptional alterations in 5xFAD hippocampus that were not corrected by the eIF2α(S51A) allele. In contrast to prior studies, our immunoblot analyses did not reveal increased levels of p-eIF2α in the hippocampus of 5xFAD mice, suggesting that elevated p-eIF2α levels are not a universal feature of AD models. Collectively, our data indicate that 5xFAD-related pathologies do not necessarily require hyperphosphorylation of eIF2α to emerge; they also show that heterozygosity for the nonphosphorylatable eIF2α(S51A) allele has limited effects on 5xFAD-related disease manifestations.