Citations

Gene expression is precisely regulated during the inflammatory response to control infection and limit the detrimental effects of inflammation. Here, we profiled global mRNA translation dynamics in the mouse primary macrophage-mediated inflammatory response and identified hundreds of differentially translated mRNAs. These mRNAs’ 3’UTRs have enriched binding motifs for several RNA-binding proteins, which implies extensive translational regulatory networks. We characterized one such protein, Zfp36, as a translation repressor. Using primary macrophages from a Zfp36-V5 epitope tagged knock-in mouse generated by CRISPR/Cas9-mediated genome editing, we found that the endogenous Zfp36 directly interacts with the cytoplasmic poly(A)-binding protein. Importantly, this interaction is required for the translational repression of Zfp36’s target mRNAs in resolving inflammation. Altogether, these results uncovered critical roles of translational regulations in controlling appropriate gene expression during the inflammatory response and revealed a new biologically relevant molecular mechanism of translational repression via modulating the cytoplasmic poly(A)-binding protein.

Background Bowel flaps are a good and reliable method to restore the continuity of the aerodigestive tract. Radiated fields, contaminated recipient sites, or depleted recipient vessels may increase the risk for ischemic injury after transfer. During ischemic events, we believe that bowel conduits with serosa have a delayed neovascularization process at its new recipient site.We conducted an ischemia/reperfusion murine model to understand the difference among bowel conduits with and without serosa. Materials and Methods Two groups of rats were compared: control group (jejunal conduit with serosa) and a target group (jejunal conduit without serosa). These conduits were harvested from the peritoneal cavity and transferred into a subcutaneous pocket. After 72 hours of transfer and pedicle ligation, histological changes related to ischemia/reperfusion were assessed. In addition, tissue markers of angiogenesis (CD34), ischemia (lactate dehydrogenase [LDH]), and inflammation (interleukin [IL]-1β and IL-6) were analyzed. Results Two groups (n = 20) of male rats were analyzed. Histology showed intact jejunal mucosa in the target group. The control group showed decreased number of mucin, globet cells, decreased height, and fragmentation of villi with the absence of intestinal glands. Markers of angiogenesis (CD34) were higher in the target group. In addition, markers of ischemia (LDH) (p = 0.0045) and inflammation (IL-1b, p = 0.0008, and IL-6, p = 0.0008) were significantly lower in the target group as compared with the control group. Conclusions In circumstances in which the recipient site does not offer an adequate and healthy bed or a vascular insult occurs, bowel flaps with less amount of serosa may be able to neovascularize faster thereby increasing its chances of survival.

Background Patients diagnosed with end-stage renal disease (ESRD) are increasing at around 5% annually. Some of these patients will require free tissue transfers to reconstruct their body after trauma or cancer resection. Comorbidities can increase the level of complexity during reconstruction. Aim Our goal is to describe the outcomes of ESRD patients under dialysis who underwent free tissue transfer for head and neck reconstruction. Methods Two cohorts were analyzed: ESRD group on dialysis and a non-ESRD control group after free tissue transfer for head and neck reconstruction. Postoperative complications and mortality were recorded. For coexisting comorbidities, we determine the presence of diabetes mellitus (DM) and peripheral vascular disease (PVD). Results In this study, 85 cases with ESRD on dialysis and 841 controls were analyzed. Most patients were aged ≤ 65 years (82.5%) and nearly 92.9% of them were men. Types of head and neck cancer were neoplasm of other and unspecified parts of the mouth followed by neoplasm of tongue, the gingiva, hypopharynx, and floor of mouth. Patients with ESRD tended to have higher rates of DM and PVD (p < 0.001) and were significantly associated with an increased risk of stroke and increased risk of 30-day mortality. However, there was no significant difference regarding flap failure among groups. Conclusion Despite greater preoperative risk factors, patients with renal failure on hemodialysis do not appear to have a higher rate of free flap failure following head and neck reconstruction. However, other complications can be minimized by optimizing patient's medical condition to succeed with this reconstructive effort.

Objective This collaboration between the American College of Rheumatology and the American Association of Hip and Knee Surgeons developed an evidence‐based guideline for the perioperative management of antirheumatic drug therapy for adults with rheumatoid arthritis (RA), spondyloarthritis (SpA) including ankylosing spondylitis and psoriatic arthritis, juvenile idiopathic arthritis (JIA), or systemic lupus erythematosus (SLE) undergoing elective total hip (THA) or total knee arthroplasty (TKA). Methods A panel of rheumatologists, orthopedic surgeons specializing in hip and knee arthroplasty, and methodologists was convened to construct the key clinical questions to be answered in the guideline. A multi‐step systematic literature review was then conducted, from which evidence was synthesized for continuing versus withholding antirheumatic drug therapy and for optimal glucocorticoid management in the perioperative period. A Patient Panel was convened to determine patient values and preferences, and the Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence and the strength of recommendations, using a group consensus process through a convened Voting Panel of rheumatologists and orthopedic surgeons. The strength of the recommendation reflects the degree of certainty that benefits outweigh harms of the intervention, or vice versa, considering the quality of available evidence and the variability in patient values and preferences. Results The guideline addresses the perioperative use of antirheumatic drug therapy including traditional disease‐modifying antirheumatic drugs, biologic agents, tofacitinib, and glucocorticoids in adults with RA, SpA, JIA, or SLE who are undergoing elective THA or TKA. It provides recommendations regarding when to continue, when to withhold, and when to restart these medications, and the optimal perioperative dosing of glucocorticoids. The guideline includes 7 recommendations, all of which are conditional and based on low‐ or moderate‐quality evidence. Conclusion This guideline should help decision‐making by clinicians and patients regarding perioperative antirheumatic medication management at the time of elective THA or TKA. These conditional recommendations reflect the paucity of high‐quality direct randomized controlled trial data.

ObjectiveThis collaboration between the American College of Rheumatology and the American Association of Hip and Knee Surgeons developed an evidence‐based guideline for the perioperative management of antirheumatic drug therapy for adults with rheumatoid arthritis (RA), spondyloarthritis (SpA) including ankylosing spondylitis and psoriatic arthritis, juvenile idiopathic arthritis (JIA), or systemic lupus erythematosus (SLE) undergoing elective total hip (THA) or total knee arthroplasty (TKA).MethodsA panel of rheumatologists, orthopedic surgeons specializing in hip and knee arthroplasty, and methodologists was convened to construct the key clinical questions to be answered in the guideline. A multi‐step systematic literature review was then conducted, from which evidence was synthesized for continuing versus withholding antirheumatic drug therapy and for optimal glucocorticoid management in the perioperative period. A Patient Panel was convened to determine patient values and preferences, and the Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence and the strength of recommendations, using a group consensus process through a convened Voting Panel of rheumatologists and orthopedic surgeons. The strength of the recommendation reflects the degree of certainty that benefits outweigh harms of the intervention, or vice versa, considering the quality of available evidence and the variability in patient values and preferences.ResultsThe guideline addresses the perioperative use of antirheumatic drug therapy including traditional disease‐modifying antirheumatic drugs, biologic agents, tofacitinib, and glucocorticoids in adults with RA, SpA, JIA, or SLE who are undergoing elective THA or TKA. It provides recommendations regarding when to continue, when to withhold, and when to restart these medications, and the optimal perioperative dosing of glucocorticoids. The guideline includes 7 recommendations, all of which are conditional and based on low‐ or moderate‐quality evidence.ConclusionThis guideline should help decision‐making by clinicians and patients regarding perioperative antirheumatic medication management at the time of elective THA or TKA. These conditional recommendations reflect the paucity of high‐quality direct randomized controlled trial data.

Vascularized toe joint transfer for finger proximal interphalangeal joint reconstruction can result in sub-optimal arc of motion and extension lag due to inappropriate intercalated bony segment length. We investigated the impact of intercalated segment length on passive arc of motion and extension lag of the reconstructed proximal interphalangeal joint. Cadaveric intercalated joint grafts were harvested from lesser toes and transferred to cadaveric fingers. The pre-determined finger proximal interphalangeal joint defect size was 2 cm. Three different intercalated segment lengths were inserted and resulting proximal interphalangeal joint arc of motion and extension lag were measured. The average arc of motion of finger proximal interphalangeal joints was 81° and 54° for toe proximal interphalangeal joints. Long intercalated segments had an average arc of motion of 30° with 32° extension lag. Equal-length intercalated segments had an average 49° arc of motion with 15° extension lag. Short intercalated segments had an average arc of motion of 71° with 8° extension lag. Shorter intercalated segments provide the greatest reduction in extension lag.

Shear wave elasticity imaging determines the mechanical parameters of soft tissue by analyzing measured shear waves induced by an acoustic radiation force. Currently, the widely used time-of-flight method calculates the correlation between shear waveforms at adjacent lateral observation points to estimate the shear elasticity value. Although this method provides accurate estimates of the shear elasticity in purely elastic media, our experience suggests that this approach overestimates the shear elasticity values in viscoelastic media because the effects of diffraction, attenuation, and dispersion are not taken into account. To address this problem, we have developed an approach that directly accounts for all of these effects when estimating the shear elasticity. This new approach simulates shear waveforms using a Green’s function-based approach with a Voigt model, while the shear elasticity and viscosity values are estimated using an optimization-based approach by comparing measured shear waveforms with simulated shear waveforms in the time-domain. This operation is then performed on a point-by-point basis to generate images. The results indicate that there is good agreement between the simulated and measured shear velocity waveforms, and that this approach yields improved images of the shear elasticity and shear viscosity. [Work supported, in part, by NIH Grant R01DK092255.]

Shear wave elastography (SWE) is clinically used for the measurement of soft tissue mechanical properties. Most SWE methods assume that the tissue is elastic, but soft tissues are inherently viscoelastic. The viscoelasticity can be characterized by examining phase velocity dispersion. Methods to extract the phase velocities from the spatiotemporal data, v(x,t), involve using a two-dimensional Fourier transform. The Fourier representation, V(k,f), is searched for peaks that correspond to the phase velocities. We present a method that uses the Multiple Signal Classification (MUSIC) method to provide robust estimation of the phase velocity dispersion curves. We compared results from the MUSIC method with the current approach of searching for peaks in the V(k,f) representation. We tested this method on digital phantom data created using finite element models (FEMs) in viscoelastic media excited by a simulated acoustic radiation force push from a curved linear array. We evaluated the algorithm with different levels of added noise. Additionally, we tested the methods on data acquired in viscoelastic phantoms with a Verasonics system. The MUSIC algorithm provided dispersion estimation with lower errors than the conventional peak search strategy. This method can be used for evaluation of wave velocity dispersion in viscoelastic tissues and guided wave propagation. [This work was supported in part by grant R01DK092255.]

Abstract BACKGROUND Cerebrospinal fluid (CSF) leak is a well-recognized complication after surgical resection of vestibular schwannomas and is associated with a number of secondary complications, including readmission and meningitis. OBJECTIVE To identify risk factors for and timing of 30-d readmission with CSF leak. METHODS Patients who had undergone surgical resection of a vestibular schwannoma from 1995 to 2010 were identified in the California Office of Statewide Health Planning and Development database. The most common admission diagnoses were identified by International Classification of Disease, ninth Revision, diagnosis codes, and predictors of readmission with CSF leak were determined using logistic regression. RESULTS A total of 6820 patients were identified. CSF leak, though a relatively uncommon cause of admission after discharge (3.52% of all patients), was implicated in nearly half of 490 readmissions (48.98%). Significant independent predictors of readmission with CSF leak were male sex (odds ratio [OR] 1.72, 95% confidence interval [CI] 1.32-2.25), first admission at a teaching hospital (OR 3.32, 95% CI 1.06-10.39), CSF leak during first admission (OR 1.84, 95% CI 1.33-2.55), obesity during first admission (OR 2.10, 95% CI 1.20-3.66), and case volume of first admission hospital (OR of log case volume 0.82, 95% CI 0.70-0.95). Median time to readmission was 6 d from hospital discharge. CONCLUSION This study has quantified CSF leak as an important contributor to nearly half of all readmissions following vestibular schwannoma surgery. We propose that surgeons should focus on technical factors that may reduce CSF leakage and take advantage of potential screening strategies for the detection of CSF leakage prior to first admission discharge.