Household Income and Parental Educational Level Affect Post-Operative Opioid Usage in Pediatric Orthopaedic Patients.

Opioid medications are commonly prescribed after pediatric orthopaedic surgery, but there is a critical need to optimize prescribing practice. This study identifies socio-economic characteristics, surgical characteristics, and patient reported psychological factors influencing postoperative opioid use in this population and found that post-operative opioid use in this pediatric orthopaedic population is multifactorial. Physicians should consider implementing protocols for initial opioid prescriptions to cover two to three days following common orthopaedic surgeries for most pediatric patients.

Primary Repair of Peroneus Longus Myofascial Herniation With Symptomatic Superficial Peroneal Nerve Compression.

Symptomatic myofascial herniations of the extremities occur infrequently; however, they can contribute to significant pain, weakness, and neuropathy with activity. Muscle herniation typically occurs through either a traumatic or congenital focal defect in the deep overlying fascia. Patients may present with an intermittently palpable subcutaneous mass and may have neuropathic symptoms, depending on the degree of nerve involvement. Patients are initially treated with conservative modalities, whereas surgery is reserved for patients who demonstrate persistent functional limitations and neurologic symptoms. Here, we demonstrate a technique for primary repair of a symptomatic lower-leg fascial defect.

Treatment-Monitoring Capabilities of Serum and Urine Biomarkers for Meniscal Allograft Transplantation in a Preclinical Canine Model.

BACKGROUND: Meniscal allograft transplantation (MAT) has been developed as a treatment for meniscal deficiency. Despite promising outcomes, there are no real-time methods to evaluate graft survivorship and predict functional outcomes. HYPOTHESIS: Assessment of serum and urine biomarkers could be used to develop biomarker panels-prognostic (1- and 3-month postsurgical time points) and diagnostic (6-month time point)-based on strong associations with clinically relevant outcome metrics obtained 6 months after surgery. STUDY DESIGN: Descriptive laboratory study. METHODS: Twelve adult purpose-bred research hounds were included and underwent medial meniscal release to induce meniscal deficiency. Three months after meniscal release surgery, medial menisci were replaced with fresh-frozen meniscus (n = 4), fresh meniscus (n = 4), or fresh meniscotibial osteochondral allograft (n = 4) such that a spectrum of pain and functional outcomes could be anticipated. Serum and urine from all dogs were collected preoperatively and at 1, 3, and 6 months after MAT surgery. Dogs were assessed for pain-related and functional outcomes at the same time points. To develop a prognostic panel of biomarkers, biomarker data from the 1- and 3-month post-MAT surgery time points were used to model 6-month clinical outcomes. A diagnostic panel of biomarkers was developed using data from the 6-month post-MAT surgery to model 6-month clinical outcomes. Primary outcomes for pain and function were visual analog scale (VAS) and operated limb percentage total pressure index (%TPI), respectively. Using random subject effects, linear mixed models were used to develop prognostic biomarker panels, and linear fixed-effect models were used to develop diagnostic biomarker panels, with variance explained for each panel reported (R2) along with individual biomarker relationships. RESULTS: Across prognostic biomarker panels, a panel including serum IL-6, IL-8, IL-10, and IL-18 was fit for the primary functional outcome, operated limb %TPI (R2 = 0.450), whereas a panel including serum CTX-II and OPG was fit for the primary pain-related outcome, VAS (R2 = 0.516). Across diagnostic biomarker panels, a panel including serum MMP-1 and MMP-3 and urine PINP and TIMP-1 was fit for %TPI (R2 = 0.863). Separately, a panel including urine CTX-I, CTX-II, IL-8, MMP-2, and TIMP-1 was fit as diagnostic biomarkers for the VAS for pain (R2 = 0.438). CONCLUSION: Biomarker panels of selected serum and/or urine proteins can model clinically relevant metrics for function and pain in a preclinical model of MAT. CLINICAL RELEVANCE: Biomarker panels could be used to provide real-time diagnostic and prognostic data regarding outcomes after MAT.

Diagnosis and Management of Articular Cartilage and Meniscus Pathology in the Posterior Cruciate Ligament-Injured Knee.

Posterior cruciate ligament (PCL) injuries commonly occur in association with participation in sporting or recreational activities or due to a direct trauma. Cartilage and meniscal lesions are prevalent in PCL-injured knees with increasing likelihood and severity based on extent and duration of trauma to the knee. As such, comprehensive diagnostics should be performed to ascertain all related pathology, and patients should be thoroughly educated regarding treatment options, likely sequelae including posttraumatic osteoarthritis, and associated outcomes. Treatments should address the joint as an organ, ensuring stability, alignment, and functional tissue restoration are optimized by the most efficient and effective means possible. Compliance with patient- and procedure-specific postoperative management protocols is critical for optimizing successful outcomes for these complex cases. The objectives of this review article are to highlight the likelihood and importance of osteochondral and meniscal pathology in the PCL-injured knee, and to provide the best current evidence regarding comprehensive evaluation and management for PCL-injured knees with cartilage and/or meniscal comorbidities.

Usage Trends of Patient-reported Outcome Measures in Shoulder Literature.

INTRODUCTION: Quantifying patient outcomes is integral in orthopaedic practice, and patient-reported outcome measures (PROMs) assist with this goal and assist clinicians in assessing subjective outcomes (pain, satisfaction, etc.). This study seeks to identify the most highly used PROMs in the shoulder literature and analyze their usage trends. METHODS: PubMed was queried for all shoulder-based articles published in eight selected journals from 2007 to 2017. Articles were assessed for PROM usage, surgical approach, surgical procedure, and disease pathology. Frequency analyses identified the most used PROMs overall, and for each approach, procedure, and pathology. Last, usage trends, question number, validation, and clinician dependence of PROMs with ≥20 uses were analyzed. RESULTS: In total, 1,740 of 2,462 articles (71%) used 105 unique PROMs 4,394 times during the study. PROM usage increased 18%, and the use of multiple PROMs increased by 20%. PROMs with a clinician component increased 21% slower than the baseline. Twenty-two PROMs (17%) had >20 uses, with the most used PROMs being the Constant-Murley Score (783), American Shoulder and Elbow Surgeons Shoulder Score (731), Visual Analog Scale (685), Simple Shoulder Test (372), and the University of California, Los Angeles, Shoulder Rating Scale (274). PROMs demonstrating the greatest usage increase were the EuroQol 5-Dimensions Questionnaire (1,282%), Shoulder Pain and Disability Index (638%), Western Ontario Rotator Cuff Index (632%), Western Ontario Osteoarthritis of the Shoulder Index (582%), and Oxford Shoulder Score (462%)-all without a clinician component. DISCUSSION: PROM usage is increasing, often with multiple PROMs being used to evaluate patient outcomes. PROMs without a clinician component are growing at higher rates than their clinician-dependent counterparts, highlighting an emphasis on patient reporting of outcomes. This study suggests that the American Shoulder and Elbow Surgeons Shoulder Score, Oxford Shoulder Score, Visual Analog Scales-all without a mandatory clinician component and high levels of use-will be the most highly used PROMs moving forward to assess shoulder function.

Trends and Characteristics of Highly Cited Articles in Proximal Humerus Fracture Research.

As the treatment of proximal humerus fractures remains controversial in the literature, this study aims to identify highly cited articles and examine trends and characteristics. Scopus was used to identify the highest cited articles of proximal humerus fracture research. SPSS 23 was used for descriptive statistics and Pearson correlations for the relationship between citation count and density. Average citation count was 233 ± 164 with an annual citation density of 14 ± 7. Total citation count was associated with total citation density, 5-year citation count, and 5-year citation density. The Journal of Bone and Joint Surgery-American produced the most articles with 15 (30%). Thirty-five articles originated in Europe. The five most represented authors published three articles each. Finally, 13 (26%) papers appear in the American Shoulder and Elbow Surgeons Curriculum Guide. This study compiles a collection of articles investigating proximal humerus fractures for future review and demonstrates citation count to be an acceptable measure of an article's contemporary academic influence. (Journal of Surgical Orthopaedic Advances 28(3):180-188, 2019).

Trends and Risk Factors in Orthopedic Lawsuits: Analysis of a National Legal Database.

Orthopedic surgeons frequently encounter medical malpractice claims. The purpose of this study was to assess trends and risk factors in lawsuits brought against orthopedic surgeons using a national legal database. A legal research service was used to search publicly available settlement and verdict reports between 1988 and 2013 by terms "orthopaedic or orthopedic" and "malpractice." Temporal trends were evaluated, and logistic regression was used to identify independent risk factors for case outcomes. A total of 1562 publicly reported malpractice cases brought against orthopedic surgeons, proceeding to trial during a 26-year period, were analyzed. The plaintiffs won 462 (30%) cases, with a mean award of $1.4 million. The frequency of litigation and pay-outs for plaintiffs increased 215% and 280%, respectively, between the first and last 5-year periods. The mean payout for plaintiff-favorable verdicts was highest in pediatrics ($2.6 million), followed by spine ($1.7 million) and oncology ($1.6 million). Fracture fixation (363 cases), arthroplasty (290 cases), and spine (231 cases) were the most commonly litigated procedures, while plaintiffs were most successful for fasciotomy (48%), infection-treating procedures (43%), and carpal tunnel release (37%). When analyzing data by state and region, adjusted for population, northeastern states had a higher frequency of lawsuits. Malpractice liability has increased during the past 3 decades while orthopedic surgeons continue to win most of the cases making it to court. As patients search for medical care via publicly available information, it is important for orthopedic surgeons to understand what aspects of their own practice carry different risks of litigation. [Orthopedics. 2019; 42(2):e260-e267.].

Early Clinical and Economic Outcomes of Prophylactic and Acute Pathologic Fracture Treatment.

INTRODUCTION: Pathologic fractures often contribute to adverse events in metastatic bone disease, and prophylactic fixation offers to mitigate their effects. This study aims to analyze patient selection, complications, and in-hospital costs that are associated with prophylactic fixation compared with traditional acute fixation after completed fracture. MATERIALS AND METHODS: The Nationwide Inpatient Sample database was queried from 2002 to 2014 for patients with major extremity pathologic fractures. Patients were divided by fixation technique (prophylactic or acute) and fracture location (upper or lower extremity). Patient demographics, comorbidities, complications, hospitalization length, and hospital charges were compared between cohorts. Preoperative variables were analyzed for potential confounding, and χ2 tests and Student's t tests were used to compare fixation techniques. RESULTS: Cumulatively, 43,920 patients were identified, with 14,318 and 28,602 undergoing prophylactic and acute fixation, respectively. Lower extremity fractures occurred in 33,582 patients, and 10,333 patients had upper extremity fractures. A higher proportion of prophylactic fixation patients were white ( P = .043), male ( P = .046), age 74 years or younger ( P < .001), and privately insured ( P < .001), with decreased prevalence of obesity ( P = .003) and/or preoperative renal disease ( P = .008). Prophylactic fixation was also associated with decreased peri- and postoperative blood transfusions ( P < .001), anemia ( P < .001), acute renal failure ( P = .010), and in-hospital mortality ( P = .031). Finally, prophylactic fixation had decreased total charges (-$3,405; P = .001), hospitalization length ( P = .004), and extended length of stay (greater than 75th percentile; P = .012). CONCLUSION: Prophylactic fixation of impending pathologic fractures is associated with decreased complications, hospitalization length, and total charges, and should be considered in appropriate patients.

Ion Mobility-Mass Spectrometry Reveals the Energetics of Intermediates that Guide Polyproline Folding.

Proline favors trans-configured peptide bonds in native proteins. Although cis/trans configurations vary for non-native and unstructured states, solvent also influences these preferences. Water induces the all-cis right-handed polyproline-I (PPI) helix of polyproline to fold into the all-trans left-handed polyproline-II (PPII) helix. Our recent work has shown that this occurs via a sequential mechanism involving six resolved intermediates [Shi, L., Holliday, A.E., Shi, H., Zhu, F., Ewing, M.A., Russell, D.H., Clemmer, D.E.: Characterizing intermediates along the transition from PPI to PPII using ion mobility-mass spectrometry. J. Am. Chem. Soc. 136, 12702-12711 (2014)]. Here, we use ion mobility-mass spectrometry to make the first detailed thermodynamic measurements of the folding intermediates, which inform us about how and why this transition occurs. It appears that early intermediates are energetically favorable because of the hydration of the peptide backbone, whereas late intermediates are enthalpically unfavorable. However, folding continues, as the entropy of the system increases upon successive formation of each new structure. When PPII is immersed in 1-propanol, the PPII→PPI transition occurs, but this reaction occurs through a very different mechanism. Early on, the PPII population splits onto multiple pathways that eventually converge through a late intermediate that continues on to the folded PPI helix. Nearly every step is endothermic. Folding results from a stepwise increase in the disorder of the system, allowing a wide-scale search for a critical late intermediate. Overall, the data presented here allow us to establish the first experimentally determined energy surface for biopolymer folding as a function of solution environment.

Gas molecule scattering & ion mobility measurements for organic macro-ions in He versus N2 environments.

A pending issue in linking ion mobility measurements to ion structures is that the collisional cross section (CCS, the measured structural parameter in ion mobility spectrometry) of an ion is strongly dependent upon the manner in which gas molecules effectively impinge on and are reemitted from ion surfaces (when modeling ions as fixed structures). To directly examine the gas molecule impingement and reemission processes and their influence, we measured the CCSs of positively charged ions of room temperature ionic liquids 1-ethyl-3-methylimidazolium dicyanamide (EMIM-N(CN)2) and 1-ethyl-3-methylimidazolium tetrafluoroborate (EMIM-BF4) in N2 using a differential mobility analyzer-mass spectrometer (DMA-MS) and in He using a drift tube mobility spectrometer-mass spectrometer (DT-MS). Cluster ions, generated via electrosprays, took the form (AB)N(A)z, spanning up to z = 20 and with masses greater than 100 kDa. As confirmed by molecular dynamics simulations, at the measurement temperature (∼300 K), such cluster ions took on globular conformations in the gas phase. Based upon their attained charge levels, in neither He nor N2 did the ion-induced dipole potential significantly influence gas molecule-ion collisions. Therefore, differences in the CCSs measured for ions in the two different gases could be primarily attributed to differences in gas molecule behavior upon collision with ions. Overwhelmingly, by comparison of predicted CCSs with selected input impingement-reemission laws to measurements, we find that in N2, gas molecules collide with ions diffusely--they are reemitted at random angles relative to the gas molecule incoming angle--and inelastically. Meanwhile, in He, gas molecules collide specularly and elastically and are emitted from ion surfaces at determined angles. The results can be rationalized on the basis of the momentum transferred per collision; in the case of He, individual gas molecule collisions minimally perturb the atoms within a cluster ion (internal motion), while in the case of N2, individual gas molecules have sufficiently large momentum to alter the internal motion in organic ions.

Selected overtone mobility spectrometry.

A new means of acquiring overtone mobility spectrometry (OMS) data sets that allows distributions of ions for a prescribed overtone number is described. In this approach, the drift fields applied to specific OMS drift regions are varied to make it possible to select different ions from a specific overtone that is resonant over a range of applied frequencies. This is accomplished by applying different fields for fixed ratios of time while scanning the applied frequency. The ability to eliminate peaks from all but a single overtone region overcomes a significant limitation associated with OMS analysis of unknowns, especially in mixtures. Specifically, a priori knowledge via selection of the overtone used to separate ions makes it possible to directly determine ion mobilities for unknown species and collision cross sections (assuming that the ion charge state is known). We refer to this selection method of operation as selected overtone mobility spectrometry (SOMS). A simple theoretical description of the SOMS approach is provided. Simulations are carried out and discussed in order to illustrate the advantages and disadvantages of SOMS compared with traditional OMS. Finally, the SOMS method (and its distinction from OMS) is demonstrated experimentally by examining a mixture of peptides generated by enzymatic digestion of the equine cytochrome c with trypsin.

Characterizing intermediates along the transition from polyproline I to polyproline II using ion mobility spectrometry-mass spectrometry.

Polyproline exists predominately as the all-cis polyproline I (PPI) helix in aliphatic alcohols, whereas the all-trans polyproline II (PPII) helix is favored in aqueous solutions. Previous ion mobility spectrometry-mass spectrometry (IMS-MS) work demonstrates that the gas-phase conformations of polyproline ions can be related to the corresponding PPI and PPII helices in solution [J. Phys. Chem. B 2004, 108, 4885]. Here, we use IMS-MS to examine the detailed intermediate steps associated with the process of Polyproline-13 (Pro13) conversion from the PPI helix to the PPII helix upon solvent exchange. Collision cross section distributions of Pro13 [M + 2H](2+) ions obtained at different transition times indicate the presence of two major conformers, identified as the PPI and PPII helices, and six conformers that appear as subpopulations of polyproline. Further analysis shows a transition mechanism with sequential cis-trans isomerizations followed by a parallel process to establish PPII and two smaller subpopulations at equilibrium. Temperature-dependent studies are used to obtain Arrhenius activation parameters for each step of the mechanism, and molecular dynamics simulations provide insight about the structures of the intermediates. It appears that prolines sequentially flip from cis to trans starting from the N-terminus. However, after the first few transitions, possible steps take place at the center of the peptide chain; subsequently, several pathways appear to be accessible at the same time. Our results reflect the existence of stable subpopulations in polyprolines and provide new insight into the structural changes during the transition process of polyproline peptides converting from PPI to PPII in aqueous solution.

Overtone mobility spectrometry: part 5. Simulations and analytical expressions describing overtone limits.

Mathematical expressions for the analytical duty cycle associated with different overtones in overtone mobility spectrometry are derived from the widths of the transmitted packets of ions under different instrumental operating conditions. Support for these derivations is provided through ion trajectory simulations. The outcome of the theory and simulations indicates that under all operating conditions there exists a limit or maximum observable overtone that will result in ion transmission. Implications of these findings on experimental design are discussed.

Using ion mobility data to improve peptide identification: intrinsic amino acid size parameters.

A new method for enhancing peptide ion identification in proteomics analyses using ion mobility data is presented. Ideally, direct comparisons of experimental drift times (t(D)) with a standard mobility database could be used to rank candidate peptide sequence assignments. Such a database would represent only a fraction of sequences in protein databases and significant difficulties associated with the verification of data for constituent peptide ions would exist. A method that employs intrinsic amino acid size parameters to obtain ion mobility predictions that can be used to rank candidate peptide ion assignments is proposed. Intrinsic amino acid size parameters have been determined for doubly charged peptide ions from an annotated yeast proteome. Predictions of ion mobilities using the intrinsic size parameters are more accurate than those obtained from a polynomial fit to t(D) versus molecular weight data. More than a 2-fold improvement in prediction accuracy has been observed for a group of arginine-terminated peptide ions 12 residues in length. The use of this predictive enhancement as a means to aid peptide ion identification is discussed, and a simple peptide ion scoring scheme is presented.

Development of high-sensitivity ion trap ion mobility spectrometry time-of-flight techniques: a high-throughput nano-LC-IMS-TOF separation of peptides arising from a Drosophila protein extract.

A linear octopole trap interface for an ion mobility time-of-flight mass spectrometer has been developed for focusing and accumulating continuous beams of ions produced by electrospray ionization. The interface improves experimental efficiencies by factors of approximately 50-200 compared with an analogous configuration that utilizes a three-dimensional Paul geometry trap (Hoaglund-Hyzer, C. S.; Lee, Y. J.; Counterman, A. E.; Clemmer, D. E. Anal. Chem. 2002, 74, 992-1006). With these improvements, it is possible to record nested drift (flight) time distributions for complex mixtures in fractions of a second. We demonstrate the approach for several well-defined peptide mixtures and an assessment of the detection limits is given. Additionally, we demonstrate the utility of the approach in the field of proteomics by an on-line, three-dimensional nano-LC-ion mobility-TOF separation of tryptic peptides from the Drosophila proteome.