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Opioid-limiting legislation has been enacted in response to the opioid epidemic in the United States. However, the impact of this legislation on perioperative opioid prescribing in elective shoulder surgery is not well understood. This is an observational review of 90-day perioperative opioid-prescription filling by patients undergoing shoulder surgery using a national insurance database (n = 231,634 patients) between 2010 and 2019. Statistics evaluated the impact of the year and opioid-limiting legislation on first prescription and cumulative 90-day opioid filling. Initial and cumulative opioid-prescription volume decreased significantly from 2010 to 2019 (49 to 44.4 initial oxycodone 5-mg equivalents, 132.8 to 72.3 cumulative oxycodone 5-mg equivalents; all p < 0.001). States with opioid-limiting legislation had larger reductions in initial and cumulative opioid-prescription filling over similar time frames (p < 0.001). Perioperative opioid prescribing has decreased significantly in shoulder surgery with time and state legislation. Individual prescribers and state and national legislators should continue to seek ways to reduce opioid overprescribing. (Journal of Surgical Orthopaedic Advances 33(3):152-157, 2024).

Objectives: In far-distal extra-articular tibia fracture "extreme" nailing, debate surrounds the relative biomechanical performance of plating the fibula compared with extra distal interlocks. This study aimed to evaluate several constructs for extreme nailing including one interlock (one medial-lateral interlock), one interlock + plate (one medial-lateral interlock with lateral fibula compression plating), and two interlocks (one medial-lateral interlock and one anterior-posterior interlock)., Methods: Fifteen pairs of fresh cadaver legs were instrumented with a tibial nail to the physeal scar. A 1 cm segment of bone was resected from the distal tibia 3.5 cm from the joint and an oblique osteotomy was made in the distal fibula. We loaded specimens with three different distal fixation constructs (one interlock, one interlock + plate, and two interlocks) through 10,000 cycles form 100N-700 N of axial loading. Load to failure (Newtons), angulation and displacement were also measured., Results: Mean load to failure was 2092 N (one interlock), 1917 N (one interlock + plate), and 2545 N (two interlocks). Linear mixed effects modeling demonstrated that two interlocks had a load to failure 578 N higher than one interlock alone (95 % CI, 74N-1082 N; P = 0.02), but demonstrated no significant difference between one interlock and one interlock + plate. No statistically significant difference in rates or timing of displacement >2 mm or angulation >10° were demonstrated., Conclusions: When nailing far-distal extra-articular tibia and fibula fractures, adding a second interlock provides more stability than adding a fibular plate. Distal fibula plating may have minimal biomechanical effect in extreme nailing., Competing Interests: Declaration of competing interest The remaining authors report no conflicts., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: Financial toxicity is highly prevalent in patients after an orthopaedic injury. However, little is known regarding the conditions that promote and protect against this financial distress. Our objective was to understand the factors that cause and protect against financial toxicity after a lower extremity fracture., Methods: A qualitative study was conducted using semi-structured interviews with 20 patients 3 months after surgical treatment of a lower extremity fracture. The interviews were audio-recorded, transcribed verbatim, and analyzed using thematic analysis to identify themes and subthemes. Data saturation occurred after 15 interviews. The percentage of patients who described the identified themes are reported., Results: A total of 20 patients (median age, 44 years [IQR, 38 to 58]; 60% male) participated in the study. The most common injury was a distal tibia fracture (n = 8; 40%). Eleven themes that promoted financial distress were identified, the most common being work effects (n = 14; 70%) and emotional health (n = 12; 60%). Over half (n = 11; 55%) of participants described financial toxicity arising from an inability to access social welfare programs. Seven themes that protected against financial distress were also identified, including insurance (n = 17; 85%) and support from friends and family (n = 17; 85%). Over half (n = 13; 65%) of the participants discussed the support they received from their healthcare team, which encompassed expectation setting and connections to financial aid and other services. Employment protection and workplace flexibility were additional protective themes., Conclusion: This qualitative study of orthopaedic trauma patients found work and emotional health-related factors to be primary drivers of financial toxicity after injury. Insurance and support from friends and family were the most frequently reported protective factors. Many participants described the pivotal role of the healthcare team in establishing recovery expectations and facilitating access to social welfare programs., (Copyright © 2024 by the American Academy of Orthopaedic Surgeons.)

Background: Studies evaluating surgical-site infection have had conflicting results with respect to the use of alcohol solutions containing iodine povacrylex or chlorhexidine gluconate as skin antisepsis before surgery to repair a fractured limb (i.e., an extremity fracture)., Methods: In a cluster-randomized, crossover trial at 25 hospitals in the United States and Canada, we randomly assigned hospitals to use a solution of 0.7% iodine povacrylex in 74% isopropyl alcohol (iodine group) or 2% chlorhexidine gluconate in 70% isopropyl alcohol (chlorhexidine group) as preoperative antisepsis for surgical procedures to repair extremity fractures. Every 2 months, the hospitals alternated interventions. Separate populations of patients with either open or closed fractures were enrolled and included in the analysis. The primary outcome was surgical-site infection, which included superficial incisional infection within 30 days or deep incisional or organ-space infection within 90 days. The secondary outcome was unplanned reoperation for fracture-healing complications., Results: A total of 6785 patients with a closed fracture and 1700 patients with an open fracture were included in the trial. In the closed-fracture population, surgical-site infection occurred in 77 patients (2.4%) in the iodine group and in 108 patients (3.3%) in the chlorhexidine group (odds ratio, 0.74; 95% confidence interval [CI], 0.55 to 1.00; P = 0.049). In the open-fracture population, surgical-site infection occurred in 54 patients (6.5%) in the iodine group and in 60 patients (7.3%) in the chlorhexidine group (odd ratio, 0.86; 95% CI, 0.58 to 1.27; P = 0.45). The frequencies of unplanned reoperation, 1-year outcomes, and serious adverse events were similar in the two groups., Conclusions: Among patients with closed extremity fractures, skin antisepsis with iodine povacrylex in alcohol resulted in fewer surgical-site infections than antisepsis with chlorhexidine gluconate in alcohol. In patients with open fractures, the results were similar in the two groups. (Funded by the Patient-Centered Outcomes Research Institute and the Canadian Institutes of Health Research; PREPARE ClinicalTrials.gov number, NCT03523962.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: The LIMB-Q is a novel patient-reported outcome measure for lower extremity trauma patients. The aim of this study was to perform a psychometric validation of the LIMB-Q based on the Rasch Measurement Theory., Methods: An international, multi-site convenience sample of patients with lower extremity traumatic injuries distal to the mid-femur were recruited via clinical sites (United States, Netherlands) and online platforms (English; Trauma Survivors Network, Prolific). A cross-sectional survey of the LIMB-Q was conducted with test-rest (TRT) measured 1-2 weeks after initial completion in a sub-group of patients., Results: The LIMB-Q was field-tested in 713 patients. The mean age was 41 years (standard deviation (SD) 17, range 18-85), mean time from injury was 7 years (SD 9, range 0-58), and there were variable injury and treatment characteristics (39% fracture surgery only, 38% flap or graft, 13% amputation, 10% amputation and flap/graft). Out of 382 items tested, 164 were retained across 16 scales. Reliability was demonstrated with person separation index values 0.80 and greater in 14 scales (0.78-0.79 in remaining 2 scales), Cronbach alpha values 0.83 and greater, and intraclass correlation coefficient values 0.70 and greater. Each scale was unidimensional, measurement invariance was confirmed across clinical and demographic factors, TRT showed adequate reliability, and construct validity was demonstrated., Conclusions: The LIMB-Q is a patient reported outcome measure with 16 independently functioning scales (6-15 items per scale) developed and validated specifically for lower extremity trauma patients with fractures, reconstruction, and/or amputation., Competing Interests: None of the authors have a conflict of interest., (Copyright © 2024 by the American Society of Plastic Surgeons.)

Background: Orthopaedic surgeons prescribe more opioid narcotics than any other surgical specialty. Proximal humerus fractures (PHF) often occur in the high-risk elderly population. The opioid epidemic has led to public policy aimed at reductions in opioid prescription. This study aimed to evaluate the impact that new legislation has had on opioid prescription patterns in patients who sustained proximal humerus fractures., Methods: A retrospective review of all patients who sustained PHF at a single academic institution from 1/1/2015-12/31/2019 was performed. A total of 762 proximal humerus fractures were identified and final analysis included 383 patients. Collected data included basic demographics and opioid prescriptions obtained through review of the electronic medical record. The North Carolina Strengthen Opioid Misuse Prevention act legislation that went into effect on July 1, 2017., Results: There was no difference in the number of pre- or postoperative opioid prescriptions provided with the new legislation. Our data showed a significant reduction in MeQs prescribed preoperatively pre-STOP act (188.1 MeQs) and post-STOP act (99.4 MeQs). There was also a significant difference in the amount of postoperative narcotics prescribed in the pre-STOP (972.6 MeQs) and post-STOP act (508.6 MeQs) groups (p < 0.01)., Conclusions: With the enactment of the STOP act in North Carolina, we have seen a significant reduction in the amount of narcotic prescribed after sustaining a proximal humerus fracture preoperatively and postoperatively. This data demonstrates the impact that implementation of state-wide regulatory changes in opioid prescribing policy has had for a common orthopedic condition., (© 2022. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Background: Race and insurance status are independent predictors of healthcare outcomes following lower-extremity trauma. Level 1 trauma centers show better outcomes overall, but it is has not been extensively studied as to whether they specifically lower complication rates and shorten length of stay in those with Black race, with low socioeconomic status, and/or a lack of private health insurance. We performed a study with the objective of determining whether Level I trauma centers can improve the complication rate of those shown to be at high risk of experiencing adverse outcomes due to socioeconomic differences., Hypothesis: Level 1 trauma centers will be successful in mitigating the disparity in complication rates and length of stay associated with racial and socioeconomic differences among trauma patients experiencing an open tibia fracture., Patients and Methods: The National Trauma Databank was reviewed from 2008 to 2015, identifying 81,855 encounters with an open tibia fracture, and 33,047 at a Level I trauma center. Regression models determined effects of race and insurance status on outcomes by trauma center while controlling for confounders., Results: Black race [OR 1.36, 95% CI, 1.17-1.58; p < 0.05] and "other" race [OR 1.28, 95% CI, 1.07-1.52; p < 0.05] were associated with higher odds of injury-specific complications. Patients without private insurance and of non-White or Black race in comparison to White patients had a significantly longer length of stay [coefficient 1.66, 95% CI, 1.37-1.94; p < 0.001]. These differences persisted in patients treated at an American College of Surgeons (ACS) Level I trauma center., Discussion: Treatment at an ACS Level I trauma center did not reduce the independent effects of race and insurance status on outcomes after open tibia fracture, emphasizing the need to recognize this disparity and improve care for at-risk populations., (© 2023 Delhi Orthopedic Association. All rights reserved.)

Introduction: Peripheral nerve blocks (PNB) has been increasingly used in the care of patients with geriatric hip fracture to reduce perioperative opiate use and the need for general anesthesia. However, the associated motor palsy may impair patients' ability to mobilize effectively after surgery and subsequently may increase latency to key mobility milestones postoperatively, as well as increase inpatient length of stay (LOS). The aim of this study was to investigate time-to-mobility milestones and length of hospital stay between peripheral, epidural, and general anesthesia., Methods: A retrospective review identified 1,351 patients aged 65 years or older who underwent surgery for hip fracture between 2012 and 2018 at a single academic health system. Patients were excluded if baseline nonambulatory, restricted weight-bearing postoperatively, or sustained concomitant injuries precluding mobilization, with a final cohort of 1,013 patients. Time-to-event analyses for discharge and mobility milestones were assessed using univariate Kaplan-Meier and multivariate Cox proportional hazard regression analyses., Results: PNB was associated with delayed postoperative time to ambulation ( P < 0.001) and time to out-of-bed ( P = 0.029), along with increased LOS ( P < 0.001). Epidural anesthesia was associated with less delay to first out-of-bed ( P = 0.002), less delay to ambulation ( P = 0.001), and overall reduced length of stay ( P < 0.001)., Discussion: PNB was associated with slower mobilization and longer hospitalization while epidural anesthesia was associated with quicker mobilization and shorter hospital stays. Epidural anesthesia may be a preferable anesthesia choice in patients with geriatric hip fracture when possible., Level of Evidence: Level III., (Copyright © 2023 by the American Academy of Orthopaedic Surgeons.)

The vulnerabilities of cancer cells constitute a promising strategy for drug therapeutics. This paper integrates proteomics, bioinformatics, and cell genotype together with in vitro cell proliferation assays to identify key biological processes and potential novel kinases that could account, at least in part, for the clinical differences observed in colorectal cancer (CRC) patients. This study started by focusing on CRC cell lines stratified by their microsatellite ( MS ) state and p53 genotype. It shows that cell-cycle checkpoint, metabolism of proteins and RNA, signal transduction, and WNT signaling processes are significantly more active in MSI-High p53-WT cell lines. Conversely, MSI-High cell lines with a mutant (Mut) p53 gene showed hyperactivation of cell signaling, DNA repair, and immune-system processes. Several kinases were linked to these phenotypes, from which RIOK1 was selected for additional exploration. We also included the KRAS genotype in our analysis. Our results showed that RIOK1's inhibition in CRC MSI-High cell lines was dependent on both the p53 and KRAS genotypes. Explicitly, Nintedanib showed relatively low cytotoxicity in MSI-High with both mutant p53 and KRAS (HCT-15) but no inhibition in p53 and KRAS WT (SW48) MSI-High cells. This trend was flipped in CRC MSI-High bearing opposite p53-KRAS genotypes (e.g., p53-Mut KRAS-WT or p53-WT KRAS-Mut), where observed cytotoxicity was more extensive compared to the p53-KRAS WT-WT or Mut-Mut cells, with HCT 116 (KRAS-Mut and p53-WT) being the most sensitive to RIOK1 inhibition. These results highlight the potential of our in silico computational approach to identify novel kinases in CRC sub-MSI-High populations as well as the importance of clinical genomics in determining drug potency.

Background: Heterotopic ossification (HO) is a common complication after surgical fixation of acetabular fractures. Numerous strategies have been employed to prevent HO formation, but results are mixed and optimal treatment strategy remains controversial. The purpose of the study was to describe current national heterotopic ossification (HO) prophylaxis patterns among academic trauma centers, determine the association between prophylaxis type and radiographic HO, and identify if heterogeneity in treatment effects exist based on outcome risk strata., Methods: We used data from a subset of participants enrolled in the Pragmatic Randomized Trial Evaluating Pre-Operative Alcohol Skin Solutions in Fractured Extremities (PREPARE) trial. We included only patients with closed AO-type 62 acetabular fractures that were surgically treated via a posterior (Kocher-Langenbeck), combined anterior and posterior, or extensile exposure. PREPARE Clinical Trial Registration Number: NCT03523962 Patient population This cohort study was nested within the Pragmatic Randomized Trial Evaluating Pre-Operative Alcohol Skin Solutions in Fractured Extremities (PREPARE) trial. The PREPARE trial is a multicenter cluster-randomized crossover trial evaluating the effectiveness of two alcohol-based pre-operative antiseptic skin solutions. All PREPARE trial clinical centers that enrolled at least one patient with a closed AO-type 62 acetabular fracture were invited to participate in the nested study., Results: 277 patients from 20 level 1 and level 2 trauma centers in the U.S. and Canada were included in this study. 32 patients (12%) received indomethacin prophylaxis, 100 patients (36%) received XRT prophylaxis, and 145 patients (52%) received no prophylaxis. Administration of XRT was associated with a 68% reduction in the adjusted odds of overall HO (OR 0.32, 95% CI, 0.14 - 0.69, p = 0.005). The overall severe HO (Brooker classes III or IV) rate was 8% for the entire cohort; XRT reduced the rate of severe HO in high-risk patients only (p=0.03)., Conclusion: HO prophylaxis patterns after surgical fixation of acetabular fractures have changed dramatically over the last two decades. Most centers included in this study did not administer HO prophylaxis. XRT was associated with a marked reduction in the rate of overall HO and the rate of severe HO in high-risk patients. Randomized trials are needed to fully elucidate the potential benefit of XRT. PREPARE Clinical Trial Registration Number: NCT03523962., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (Copyright © 2023. Published by Elsevier Ltd.)

The characteristics that contribute to opioid demand in pelvic and acetabular fracture surgery are not well understood. We hypothesize that fracture pattern and psychiatric comorbidities will be associated with increased opioid demand. This study evaluated perioperative opioid prescription filling in 743 patients undergoing operative fixation of pelvic and acetabular injuries. Multivariable linear and logistic regression models were used to evaluate associations between baseline factors and opioid outcomes. Patients filled prescriptions for 111.2, 89.3, and 200.3 oxycodone 5-mg pills at the 1-month preop to 90-days postop, 3-months postop to 1-year postop, and 1-month preop to 1-year postop timeframes. Operatively treated wall, transverse and two-column acetabular fractures were associated with the highest opioid demand. Drug abuse and pre-injury opioid use were the primary non-surgical drivers of opioid demand. Acetabular fractures, pre-injury opioid filling, and drug abuse were the main risk factors for increased perioperative opioid prescription filling. Level of Evidence: Level III, retrospective, prognostic cohort study. (Journal of Surgical Orthopaedic Advances 32(1):041-046, 2023).

Purpose: Regional anesthesia (RA) is commonly used in distal radius fracture surgery to reduce pain and opioid consumption. The purpose of this study was to evaluate the real-world impact of RA on inpatient and outpatient opioid consumption and demand in patients undergoing distal radius fracture surgery., Methods: All patients ages 18 and older undergoing distal radius fracture surgery between 7/2013 and 7/2018 at a single institution ( n  = 969) were identified. Inpatient opioid consumption and outpatient opioid prescribing in oxycodone 5-mg equivalents (OE's) up to 90-d post-operative were recorded for patients with and without RA. Adjusted models were used to evaluate the impact of RA on opioid outcomes., Results: Adjusted models demonstrated decreases in inpatient opioid consumption in patients with RA (10.7 estimated OE's without RA vs. 7.6 OE's with RA from 0 to 24 h post-op, 10.2 vs. 5.3 from 24 to 48 h post-op and 7.5 vs. 5.0 from 48 to 72 h post-op, p <.05). Estimated cumulative outpatient opioid demand was significantly higher in patients with RA (65.3 OE's without RA vs. 81.0 with RA from 1-month pre-op to 2-week post-discharge, 76.1 vs. 87.7 OE's to 6-weeks, and 80.8 vs. 93.5 OE's to 90-d, all p values for RA <.05) though rates of refill were significantly lower in patients with RA from 2-week to 6-week post-op compared to patients without RA., Conclusions: Patients undergoing RA in distal radius fracture surgery had decreased inpatient opioid consumption but increased outpatient demand after adjustment for patient and operative characteristics., Level of Evidence: Level III, retrospective, therapeutic cohort study.

Introduction: Regional anesthesia (RA) is used reduce pain in proximal humerus and humeral shaft fracture surgery. The study hypothesis was that RA would decrease opioid demand in patients undergoing fracture surgery., Materials and Methods: Opioid demand was recorded in all patients ages 18 and older undergoing proximal humerus or humeral shaft fracture surgery at a single, Level I trauma center from 7/2013 - 7/2018 (n = 380 patients). Inpatient opioid consumption from 0-24, 24-48, and 48-72 h and outpatient opioid demand from 1-month pre-operative to 90-days post-operative were converted to oxycodone 5-mg equivalents (OE's). Unadjusted and adjusted models were constructed to evaluate the impact of RA and other factors on opioid utilization., Results: Adjusted models demonstrated increases in inpatient opioid consumption in patients with RA (6.8 estimated OE's without RA vs 8.8 estimated OE's with RA from 0-24 h post-op; 10 vs 13.7 from 24-48 h post-op; and 8.7 vs 11.6 from 48-72 h post-op; all p  < 0.05). Estimated cumulative outpatient opioid demand was significantly higher in patients with RA at all timepoints., Discussion: In proximal humerus and humeral shaft fracture surgery, RA was associated with increased inpatient and outpatient opioid demand after adjusting for baseline patient and treatment characteristics., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Purpose: The purpose of this study was to examine the differences in functional outcomes between direct and indirect surgical fixation methods of the posterior malleolus in the setting of trimalleolar fractures and identify any variables affecting patient outcomes., Methods: Primary outcomes were evaluated by PROMIS scores for short-term outcomes regarding total pain (TP) and total function (TF) comparing 40 patients with direct fixation with 77 with indirect fixation. Continuous variables were analyzed using t tests for parametric variables and the Mann-Whitney U test for nonparametric variables. Categorical variables were analyzed using a χ 2 test. Univariate and multivariate linear regression models were performed to analyze factors that affect outcomes of TP and TF., Results: There was no difference in TP or TF between groups ( P = 0.65 vs. P = 0.19). On univariate linear regression for TP, BMI, incidence of complication, tobacco use, and open injury showed significance in increasing pain levels with open injuries providing the greatest effect (coef = 11.8). On multivariate analysis, BMI, incidence of complication, open injury, and tourniquet time all significantly increased pain. For TF, univariate analysis showed age, BMI, incidence of complication, and diabetes to decrease function, and use of external fixator and tourniquet time increased function. In the multivariate model, increased BMI, open injuries, and increasing tourniquet time all decreased TF while use of an external fixator increased TF., Conclusion: This study showed no difference in TP and TF using the PROMIS outcome scores when comparing direct fixation versus indirect fixation under univariate and multivariate models., Level of Evidence: Therapeutic III., Competing Interests: The authors report no conflict of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Introduction: Limb-threatening injuries can have a profound impact on patient lives. The impact on a patient's psychosocial well-being is widespread yet not well understood. This study aims to explore which psychosocial elements are central to patient experiences after limb-threatening lower extremity trauma., Patients and Methods: This is a qualitative interview-based study to identify psychosocial experiences after limb-threatening lower extremity trauma in a patient-centered manner. Data were collected via semi-structured qualitative interviews and analyzed via an interpretive description approach. Interviews were performed until content saturation was reached., Results: A total of 33 interviews were performed until reaching content saturation. Eleven participants underwent early amputation, 7 delayed amputation after an attempt at limb salvage, and 15 underwent limb salvage. A total of 533 unique psychosocial codes were identified, comprised of eight concepts: acceptance, body image, coping, distress, positive impact, emotional support, isolation, and intrapsychic., Conclusions: This study identified the concerns central to this patient population and developed a conceptual framework for how patients cope with these psychosocial experiences. These findings underscore the importance of developing resilience by actively practicing acceptance and reaching more positive mental health outcomes. Additionally, these findings highlight the importance of increasing access to early and routine psychological and social support for patients with severe lower extremity trauma., Competing Interests: Declaration of Competing Interest There are no relevant conflicts of interest for any of the authors., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Patients with pelvic and acetabular fractures often have considerable pain in the perioperative period. Regional anesthesia (RA) including peripheral nerve blocks and spinal analgesia may reduce pain. However, the real-world impact of these modalities on inpatient opioid consumption and outpatient opioid demand is largely unknown. The purpose of this study was to evaluate the impact of perioperative RA on inpatient opioid consumption and outpatient opioid demand., Methods: This is a retrospective, observational review of inpatient opioid consumption and outpatient opioid demand in all patients ages 18 and older undergoing operative fixation of pelvic and acetabular fractures at a single Level, I trauma center from 7/1/2013-7/1/2018 (n = 205). Unadjusted and adjusted analyses were constructed to evaluate the impact of RA on inpatient opioid consumption and outpatient opioid demand while controlling for age, sex, race, body mass index (BMI), smoking, chronic opioid use, ASA score, injury mechanism, additional injuries, open injury, and additional inpatient surgery., Results: Adjusted models demonstrated increases in inpatient opioid consumption in patients with RA (12.6 estimated OE's without RA vs 16.1 OE's with RA from 48 to 72 h post-op, p < 0.05) but no significant differences at other timepoints (17.5 estimated OE's without RA vs 16.8 OE's with RA from 0 to 24 h post-op, 15.3 vs 17.1 from 24 to 48 h post-op, p > 0.05). Estimated cumulative outpatient opioid demand was significantly higher in patients with RA at discharge to 90 days post-op (and 156.8 vs 207.9 OE's to 90 days, p < 0.05) but did not differ significantly before that time (121.5 OE's without RA vs 123.9 with RA from discharge to two weeks, 145.2 vs 177.2 OE's to 6 weeks, p > 0.05)., Discussion: In pelvis and acetabulum fracture surgery, RA was associated with increased inpatient and outpatient opioid demand after adjusting for baseline patient and treatment characteristics. Regional anesthesia may not be beneficial for these patients., (© 2021. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Background: Titinopathies are inherited muscular diseases triggered by genetic mutations in the titin gene. Muscular dystrophy with myositis (mdm) is one such disease caused by a LINE repeat insertion, leading to exon skipping and an 83-amino acid residue deletion in the N2A-PEVK region of mouse titin. This region has been implicated in a number of titin-titin ligand interactions, hence are important for myocyte signaling and health. Mice with this mdm mutation develop a severe and progressive muscle degeneration. The range of phenotypic differences observed in mdm mice shows that the deletion of this region induces a cascade of transcriptional changes extending to numerous signaling pathways affected by the titin filament. Previous research has focused on correlating phenotypic differences with muscle function in mdm mice. These studies have provided understanding of the downstream physiological effects resulting from the mdm mutation but only provide insights on processes that can be physiologically observed and measured. We used differential gene expression (DGE) to compare the transcriptomes of extensor digitorum longus (EDL), psoas and soleus muscles from wild-type and mdm mice to develop a deeper understand of these tissue-specific responses., Results: The overall expression pattern observed shows a well-differentiated transcriptional signature in mdm muscles compared to wild type. Muscle-specific clusters observed within the mdm transcriptome highlight the level of variability of each muscle to the deletion. Differential gene expression and weighted gene co-expression network analysis showed a strong directional response in oxidative respiration-associated mitochondrial genes, which aligns with the poor shivering and non-shivering thermogenesis previously observed. Sln, which is a marker associated with shivering and non-shivering thermogenesis, showed the strongest expression change in fast-fibered muscles. No drastic changes in MYH expression levels were reported, which indicated an absence of major fiber-type switching events. Overall expression shifts in MYH isoforms, MARPs, and extracellular matrix associated genes demonstrated the transcriptional complexity associated with mdm mutation. The expression alterations in mitochondrial respiration and metabolism related genes in the mdm muscle dominated over other transcriptomic changes, and likely account for the late stage cellular responses in the mdm muscles., Conclusions: We were able to demonstrate that the complex nature of mdm mutation extends beyond a simple rearrangement in titin gene. EDL, psoas and soleus exemplify unique response modes observed in skeletal muscles with mdm mutation. Our data also raises the possibility that failure to maintain proper energy homeostasis in mdm muscles may contribute to the pathogenesis of the degenerative phenotype in mdm mice. Understanding the full disease-causing molecular cascade is difficult using bulk RNA sequencing techniques due to intricate nature of the disease. The development of the mdm phenotype is temporally and spatially regulated, hence future studies should focus on single fiber level investigations., (© 2022. The Author(s).)

The conformational sensitivity of intrinsically disordered proteins to shifts in pH due to their high degree of charged residues has been recognized for well over a decade. However, the role of the non-ionizable residues in this pH sensitivity remains poorly understood. Our lab has been investigating the pH sensitivity of the poly-E motifs of the PEVK region of the muscle protein titin, which provides an ideal model system to explore this question. Using a series of 15-amino acid peptides derived from one of the poly-E motif sequences, we have investigated the role of side-chain chemistry in the conformational flexibility of this region. Our results demonstrate that aromatic side chains and proline content are the two variables that most influence pH sensitivity. The introduction of aromatic side chains resulted in a more collapsed structure, even at pH 7, while the removal of prolines resulted in a higher degree of pH sensitivity. These results highlight the importance of considering the impact of non-ionizable residues on IDP function, especially when considering the impact of pH on conformational flexibility.

Muscular dystrophy with myositis ( mdm ) is a naturally occurring mutation in the mouse Ttn gene that results in higher passive stress in muscle fibers and intact muscles compared to wild-type (WT). The goal of this study was to test whether alternative splicing of titin exons occurs in mdm muscles, which contain a small deletion in the N2A-PEVK regions of titin, and to test whether splicing changes are associated with an increase in titin-based passive tension. Although higher levels of collagen have been reported previously in mdm muscles, here we demonstrate alternative splicing of titin in mdm skeletal muscle fibers. We identified Z-band, PEVK, and C-terminus Mex5 exons as splicing hotspots in mdm titin using RNA sequencing data and further reported upregulation in ECM-associated genes. We also treated skinned mdm soleus fiber bundles with trypsin, trypsin + KCl, and trypsin + KCL + KI to degrade titin. The results showed that passive stress dropped significantly more after trypsin treatment in mdm fibers (11 ± 1.6 mN/mm 2 ) than in WT fibers (4.8 ± 1 mN/mm 2 ; p = 0.0004). The finding that treatment with trypsin reduces titin-based passive tension more in mdm than in WT fibers supports the hypothesis that exon splicing leads to the expression of a stiffer and shorter titin isoform in mdm fibers. After titin extraction by trypsin + KCl + KI, mdm fibers (6.7 ± 1.27 mN/mm 2 ) had significantly higher collagen-based passive stress remaining than WT fibers (2.6 ± 1.3 mN/mm 2 ; p = 0.0014). We conclude that both titin and collagen contribute to higher passive tension of mdm muscles., Competing Interests: The authors declare no conflict of interest.

Introduction: Regional anesthesia (RA) is sometimes used to decrease pain and opioid consumption in distal femur fractures. However, the real-world impact of RA on inpatient opioid consumption and outpatient opioid demand is not well known. The hypothesis of this study is that RA would be associated with decreased inpatient opioid consumption and outpatient opioid demand., Methods: This study evaluated inpatient post-operative opioid consumption (0-24 h, 24-48 h, 48-72 h) and outpatient opioid demand (discharge to 2 weeks, 6 weeks, and 90 days) in all patients ages 18 and older undergoing operative treatment of distal femur fractures at a single institution from 7/2013 to 7/2018 (n = 230). Unadjusted and adjusted multivariable models were used to evaluate the impact of RA and other baseline patient and operative characteristics on inpatient opioid consumption and outpatient opioid demand., Results: Adjusted models demonstrated a small, significant increase in inpatient opioid consumption in patients with RA compared to no RA (4.7 estimated OE's without RA vs 6.2 OE's with RA from 24- to 48-h post-op, p < 0.05) but otherwise no significant differences at other timepoints (6.7 estimated OE's without RA vs 6.9 OE's with RA from 0- to 24-h post-op and 4.5 vs 4.4 from 48- to 72-h post-op, p > 0.05). Estimated cumulative outpatient opioid demand was significantly higher in patients with RA from discharge to 6 weeks and to 90 days (55.8 OE's without RA vs 63.9 with RA from discharge to 2 weeks, p > 0.05; 74.9 vs 95.1 OE's to 6 weeks, and 85 vs 113.1 OE's to 90 days, p < 0.05)., Discussion: In distal femur fracture surgery, RA was associated with increased inpatient and outpatient opioid demand after adjusting for baseline patient and treatment characteristics. These results call into question the routine use of RA in distal femur fractures., Level of Evidence: Level III, retrospective, therapeutic cohort study., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Hip fracture surgery is painful, and regional anesthesia (RA) has been used in an attempt to reduce pain and opioid consumption after surgery. Despite potential analgesic benefits, the effect of RA on inpatient and outpatient opioid demand is not well known. We hypothesized that RA would be associated with decreased inpatient opioid demand and has little effect on outpatient opioid demand in hip fracture surgery., Methods: This study retrospectively evaluated all patients of 18 years and older undergoing hip fracture surgery from July 2013 to July 2018 at a single, level I trauma center (n = 1,659). Inpatient opioid consumption in 24-hour increments up to 72-hour postoperative and outpatient opioid prescribing up to 90-day postoperative were recorded in oxycodone 5-mg equivalents (OE's). Adjusted models evaluated the effect of RA on opioid demand after adjusting for other baseline and treatment variables., Results: After adjusting for baseline and treatment variables, there were small increases in inpatient opioid consumption in patients with RA (2.6 estimated OE's without RA versus three OE's with RA from 0 to 24 hours postoperatively, 2.1 versus 2.4 from 24 to 48 hours postoperatively, and 1.6 versus 2.2 from 48 to 72 hours postoperatively, all P values for RA <0.001). However, there were no notable differences in outpatient opioid demand., Discussion: RA did not decrease inpatient or outpatient opioid demand in patients undergoing hip fracture surgery in this pragmatic study. In fact, there were slight increases in inpatient opioid consumption, although these differences are likely clinically insignificant. These results temper enthusiasm for RA in hip fracture surgery., Level of Evidence: Level III, retrospective, therapeutic cohort study., (Copyright © 2022 by the American Academy of Orthopaedic Surgeons.)

Introduction: The role of deltoid ligament repair is controversial in the treatment of bimalleolar equivalent ankle injuries. Our purpose was to compare midterm functional outcomes and reoperation rates of unstable distal fibula fractures treated with open reduction internal fixation (ORIF) of the fibula and either deltoid ligament repair, trans-syndesmotic fixation, or combined fixation., Methods: Skeletally mature subjects were retrospectively identified after fixation of isolated unstable distal fibula fractures treated at a single academic level 1 hospital from January 2005 to May 2019. The AAOS Foot and Ankle Module outcomes questionnaire (AAOS-FAM) was obtained at a mean time from surgery of 4.6 +/- 3.1 years. Subjects underwent one of three methods of fixation including distal fibula ORIF and one of the following: trans-syndesmotic fixation (N = 66), deltoid ligament repair (N = 16), or combined trans-syndesmotic fixation and deltoid ligament repair (N = 26). Outcomes scores and Charlson Comorbidity Index scores were compared between groups by Kruskal-Wallis testing for non-normally distributed data. Rates of reoperation were compared by Fisher's exact test. Statistical significance was set to P < 0.05 for all comparisons., Results: There was no significant difference in AAOS-FAM scores between the three groups (P = 0.18). No subjects in the deltoid ligament repair group underwent reoperation compared to 17 (26%) in the trans-syndesmotic fixation group and six (23%) in the combined fixation group. The most common reason for reoperation was removal of hardware, which was performed in 12 (18%) subjects in the trans-syndesmotic fixation group and three (12%) subjects in the combined fixation group., Conclusions: Direct deltoid ligament repair yields similar functional scores and fewer reoperations compared to trans-syndesmotic fixation at midterm follow up. Deltoid ligament repair may be a favorable treatment strategy when considering trans-syndesmotic fixation in the surgical treatment of unstable distal fibula fractures., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Psychological distress after orthopaedic trauma negatively affects patient outcomes. Resilience may mediate distress and therefore be associated with post-operative outcomes, including opioid use. The purpose of this study is to evaluate the relationship between resilience and post-operative opioid demand with the hypothesis that low levels of resilience are associated with increased opioid consumption., Materials and Methods: Patients age 18 - 65 at a single, tertiary care level 1 trauma center who underwent operative treatment of pelvic and/ or extremity fractures between 3/2017 - 6/2018 were contacted by phone to complete the OSPRO-YF, a ten-item screening tool that assesses psychological distress. Participants were screened for scores in the worst quartile (i.e., yellow flag) for resilience. Baseline patient and injury characteristics and opioid demand were compared between patients with and without positive yellow flags for resilience using Wilcoxon rank-sum for continuous variables and Fisher exact test for categorical variables., Results: A total of 117 patients were surveyed. Patients with positive yellow flag screening scores for resilience had significantly higher opioid demand, number of opioid prescriptions filled, and were more likely to refill prescriptions long-term (3-months post-discharge to one-year post-discharge). Patients with a positive yellow flag for resilience had a significantly higher number of opioid prescriptions filled in the cumulative (one-month pre-op to one-year post-discharge) time period., Discussion/ Conclusion: Lower long-term resilience scores were associated with higher postoperative opioid consumption, fill and refill rates. These results suggest low resilience may be a risk factor for increased long-term opioid consumption following surgical treatment for orthopaedic trauma., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Regional anesthesia (RA) has been used to reduce pain and opioid usage in elective orthopedic surgery. The hypothesis of this study was that RA would be associated with decreased opioid demand in tibial plateau fracture surgery., Methods: Inpatient opioid consumption and 90-day outpatient opioid prescribing in all patients ≥18 years of age undergoing tibial plateau fracture surgery from July 2013 to July 2018 (n = 264) at a single, level I trauma center were recorded. The presence or absence of perioperative RA was noted. Of 60 patients receiving RA, 52 underwent peripheral nerve blockade (PNB) with single-shot sciatic-popliteal (40.0%; n = 24), femoral (26.7%; n = 16), adductor canal (18.3%; n = 11), or fascia iliaca (1.7%; n = 1) block with ropivacaine. Ten patients received epidural analgesia (EA) with either single-shot spinal (11.7%; n = 7) blocks or continuous epidural (5.0%; n = 3). Additional baseline and treatment characteristics were recorded, including age, sex, race, body mass index (BMI), smoking, chronic opioid use, American Society of Anesthesiologists (ASA) score, injury mechanism, additional injuries, open injury, and additional inpatient surgery. Statistical models, including multivariable generalized linear models with propensity score weighting to adjust for baseline patient and treatment characteristics, were used to assess perioperative opioid demand with and without RA., Results: RA was associated with reduced inpatient opioid usage from 0 to 24 hours postoperatively of approximately 5.2 oxycodone 5-mg equivalents (0.74 incident rate ratio [IRR]; 0.63-0.86 CI; P < .001) and from 24 to 48 hours postoperatively of approximately 2.9 oxycodone 5-mg equivalents (0.78 IRR; 0.64-0.95 CI; P = .014) but not at 48 to 72 hours postoperatively. From 1 month preoperatively to 2 weeks postoperatively, RA was associated with reduced outpatient opioid prescribing of approximately 24.0 oxycodone 5-mg equivalents (0.87; 0.75-0.99; P = .044) and from 1 month preoperatively to 90 days postoperatively of approximately 44.0 oxycodone 5-mg equivalents (0.83; 0.71-0.96; P = .011), although there was no significant difference from 1 month preoperatively to 6 weeks postoperatively. There were no cases of acute compartment syndrome in this cohort., Conclusions: In tibial plateau fracture surgery, RA was associated with reduced inpatient opioid consumption up to 48 hours postoperatively and reduced outpatient opioid demand up to 90 days postoperatively without an associated risk of acute compartment syndrome. RA should be considered for patients undergoing tibial plateau fracture fixation., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 International Anesthesia Research Society.)

The disordered PEVK region of titin contains two main structural motifs: PPAK and poly-E. The distribution of these motifs in the PEVK region contributes to the elastic properties of this region, but the specific mechanism of how these motifs work together remains unclear. Previous work from our lab has demonstrated that 28-amino acid peptides of the poly-E motif are sensitive to shifts in pH, becoming more flexible as the pH decreases. We extend this work to longer poly-E constructs, including constructs containing PPAK motifs. Our results demonstrate that longer poly-E motifs have a much larger range of pH sensitivity and that the inclusion of the PPAK motif reduces this sensitivity. We also demonstrate that binding calcium can increase the conformational flexibility of the poly-E motif, though the PPAK motif can block this calcium-dependent change. The data presented here suggest a model where PPAK and calcium can alter the stiffness of the poly-E motif by modulating the degree of charge repulsion in the glutamate clusters.

Introduction: Regional anesthesia (RA) is commonly used in ankle and distal tibia fracture surgery. However, the pragmatic effects of this treatment on inpatient and outpatient opioid demand are unclear. The hypothesis was that RA would decrease inpatient opioid consumption and have little effect on outpatient demand in patients undergoing ankle and distal tibia fracture surgery compared with patients not receiving RA., Methods: All patients aged 18 years and older undergoing ankle and distal tibia fracture surgery at a single institution between July 2013 and July 2018 were included in this study (n = 1310). Inpatient opioid consumption (0-72 hours postoperatively) and outpatient opioid prescribing (1 month preoperatively to 90 days postoperatively) were recorded in oxycodone 5-mg equivalents (OEs). Adjusted models were used to evaluate the impact of RA versus no RA on inpatient and outpatient opioid demand., Results: Patients without RA had higher rates of high-energy mechanism of injury, additional injuries, open fractures, and additional surgery compared with patients with RA. Adjusted models demonstrated decreased inpatient opioid consumption in patients with RA (12.1 estimated OEs without RA vs 8.8 OEs with RA from 0 to 24 hours postoperatively, P < .001) but no significant difference after that time (9.7 vs 10.4 from 24 to 48 hours postoperatively, and 9.5 vs 8.5 from 48 to 72 hours postoperatively). Estimated cumulative outpatient opioid demand was significantly increased in patients receiving RA at all time points (112.5 OEs without RA vs 137.3 with RA from 1 month preoperatively to 2 weeks, 125.6 vs 155.5 OEs to 6 weeks, and 134.6 vs 163.3 OEs to 90 days, all P values for RA <.001)., Discussion: In ankle and distal tibia fracture surgery, RA was associated with decreased early inpatient opioid demand but significantly increased outpatient demand after adjusting for baseline patient and treatment characteristics. This study encourages the use of RA to decrease inpatient opioid use, although there was a worrisome increase in outpatient opioid demand., Level of Evidence: Level III: Retrospective, therapeutic cohort study .

Objectives: To evaluate the prevalence of post-traumatic stress disorder (PTSD) symptoms in individuals who are further removed from injury (up to 3 years) and to identify injury-specific characteristics that are associated with an increased risk for persistent PTSD symptoms., Design: Cross-sectional, retrospective cohort., Setting: Level I trauma center., Patients/participants: Two hundred forty-three patients operatively treated for orthopaedic trauma between March 2017 through June 2018., Intervention: Orthopaedic trauma requiring operative intervention., Main Outcome Measurements: The primary outcome was score on the PTSD Checklist for the DSM-5 (PCL-5) survey. A score of 31 or higher was considered concerning for PTSD., Results: Forty-nine of 239 respondents (20.5%) scored positive for PTSD. Multivariate analysis demonstrated an increased risk of PTSD for patients with a history of smoking and those who required delayed reoperation (greater than 90 days postoperative). White race and low-energy mechanisms of injury were associated with decreased risk of PTSD. Fracture locations were not associated with a higher likelihood of PTSD., Conclusions: The prevalence of PTSD symptoms in patients up to 3 years after surgery remains higher than the estimated prevalence of PTSD in the general US population. It is similar to previously documented rates of PTSD for patients less than 1 year after injury. Long-term complication requiring reoperation was associated with an increased risk of persistent PTSD symptoms. Orthopaedic providers should be mindful of PTSD symptoms not only in the immediate postoperative period but throughout the treatment course particularly for those with identified PTSD risk factors., Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Hypothesis: Regional anesthesia (RA) can be used to manage perioperative pain in the treatment of periarticular elbow fracture fixation. However, the opioid-sparing benefit is not well-characterized. The hypothesis of this study was that RA had reduced inpatient opioid consumption and outpatient opioid demand in patients who had undergone periarticular elbow fracture surgery., Methods: This study retrospectively reviews inpatient opioid consumption and outpatient opioid demand in all patients aged ≥18 years at a single Level I trauma center undergoing fixation of periarticular elbow (distal humerus and proximal forearm) fracture surgery (n=418 patients). In addition to RA vs. no RA, additional patient and operative characteristics were recorded. Unadjusted and adjusted models were constructed to evaluate the impact of RA and other factors on inpatient opioid consumption and outpatient opioid demand., Results: Adjusted models demonstrated decreases in inpatient opioid consumption postoperation in patients with RA (13.7 estimated oxycodone 5-mg equivalents or OEs without RA vs. 10.4 OEs with RA from 0 to 24 hours postoperation, P = .003; 12.3 vs. 9.2 OEs from 24 to 48 hours postoperation, P = .045). Estimated cumulative outpatient opioid demand differed significantly in patients with RA (166.1 vs. 132.1 OEs to 6 weeks, P = .002; and 181 vs. 138.6 OEs to 90 days, P < .001)., Discussion: In proximal forearm and distal humerus fracture surgery, RA was associated with decreased inpatient and outpatient opioid demand after adjusting for baseline patient and treatment characteristics. These results encourage utilization of perioperative RA to reduce opioid use., (Copyright © 2021 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background: The impact of time and state regulation on opioid prescribing in orthopedic trauma is not well known. The purpose of this study is to evaluate the impact of time and state-level opioid legislation on 90-day perioperative opioid prescribing in ankle fracture surgery from 2010 to 2019., Methods: This is a retrospective, cohort study using a national insurance database including commercial insurance, Medicare, Medicaid, and cash pay patients to evaluate 30-day pre-operative to 90-day post-operative opioid prescription filling in 40,286 patients ages 18 and older undergoing Current Procedural Terminology codes 27,766, 27,769, 27,792, 27,814, 27,822, and/or 27,823 between 2010 and 2019 in all 50 United States. The primary study outcome was initial and cumulative perioperative opioid prescription filling and rates of filling and refills over the study timeframe., Results: Mean first prescription volume has not changed dramatically from 2010 (37 oxycodone 5 mg pills) to 2019 (33.3 oxycodone 5 mg pills). However, cumulative prescriptions within the 30PRE-90POST timeframe have decreased considerably from 2010 (128.5 oxycodone 5 mg pills) to 2019 (70.4 oxycodone 5 mg pills), and cumulative prescription filling in years 2018 and 2019 was significantly less than in 2010. Legislation targeting duration or duration and volume had the largest impacts on initial and cumulative opioid prescribing., Conclusions: In ankle fracture surgery, states with opioid prescribing legislation had larger reductions in perioperative opioid prescribing compared to states without opioid legislation. Legislation targeting duration or duration and volume had the largest impacts on opioid prescribing., Level of Evidence: Level III, Retrospective prognostic cohort study., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Titin, the largest muscle protein, plays an important role in passive tension, sarcomeric integrity and cell signaling within the muscle. Recent work has also highlighted a role for titin in active muscle and the N2A region found in skeletal muscle titin and in some isoforms of cardiac titin has been linked to this function. The N2A region is a multi-domain region composed of four immunoglobulin domains (I80-I83) and a disordered region called the insertion sequence. Previously, our lab has shown that the N2A region binds F-actin in a calcium dependent manner, but it is not known which domains within this region are critical for this binding to occur. In this work, we have used co-sedimentation to demonstrate that only constructs containing the I80 domain are capable of binding F-actin. In addition, binding was only observed in constructs containing at least 3 immunoglobulin domains suggesting a length-dependence to binding. Finally, the calcium-dependence of N2A binding is lost when I83 is not present, consistent with the calcium stabilization that has been reported for this domain. Based on these results, we propose that I80 is critical for initiating binding to F-actin and that I83 is responsible for the calcium dependence., Competing Interests: Declaration of competing interest The authors do not have any conflict of interests associated with this project., (Copyright © 2021 Elsevier Inc. All rights reserved.)

While protein refolding has been studied for over 50 years since the pioneering work of Christian Anfinsen, there have been a limited number of studies correlating results between chemical, thermal, and mechanical unfolding. The limited knowledge of the relationship between these processes makes it challenging to compare results between studies if different refolding methods were applied. Our current work compares the energetic barriers and folding rates derived from chemical, thermal, and mechanical experiments using an immunoglobulin-like domain from the muscle protein titin as a model system. This domain, I83, has high solubility and low stability relative to other Ig domains in titin, though its stability can be modulated by calcium. Our experiments demonstrated that the free energy of refolding was equivalent with all three techniques, but the refolding rates exhibited differences, with mechanical refolding having slightly faster rates. This suggests that results from equilibrium-based measurements can be compared directly but care should be given comparing refolding kinetics derived from refolding experiments that used different unfolding methods.

Introduction: Regional anesthesia (RA) may be used in femoral shaft fracture surgery to decrease pain and opioid consumption. However, the impact of RA on inpatient and outpatient opioid demand in patients undergoing femoral shaft fracture surgery is largely unknown. The aim of this study was to evaluate the impact of RA on inpatient opioid consumption and outpatient opioid demand in patients undergoing femoral shaft fracture surgery., Methods: Inpatient opioid consumption and outpatient opioid demand in all patients undergoing femoral shaft fracture surgery was recorded at a single, Level I trauma center from 7/2013 - 7/2018 (n=436). In addition to RA, baseline and treatment factors including age, sex, race, body mass index (BMI), smoking, chronic opioid use, American Society of Anesthesiologists (ASA) score, injury mechanism, additional injuries, open injury, and additional inpatient surgery were recorded. Unadjusted and adjusted multivariable models were used to evaluate the impact of RA on inpatient opioid consumption and outpatient opioid demand., Results: Adjusted models demonstrated increases in inpatient opioid consumption in patients with RA (6.9 estimated OE's without RA vs 8.8 OE's with RA from 48-72 hours post-op, p<0.05) but no significant differences at other timepoints (10.3 estimated OE's without RA vs 9.2 OE's with RA from 0-24 hours post-op, 8.2 vs 8.8 from 24-48 hours post-op, p>0.05). Estimated cumulative outpatient opioid demand did not differ significantly in patients with RA (82.3 OE's without RA vs 94.8 with RA from discharge to two-weeks, 105.4 vs 116.3 OE's to 6-weeks, and 124.5 vs 137.9 OE's to 90-days, all p>0.05). Late opioid refills were significantly more common in patients with RA (1.57 odds at 2-weeks to 6-weeks, 1.69 odds at 6-weeks to 90-days, p<0.05) DISCUSSION: In femoral shaft fracture surgery, RA was not associated with decreased opioid demand after adjusting for baseline patient and treatment characteristics. These results provide a real-world estimate of the impact of RA on opioid demand in femoral shaft fracture surgery and encourage providers to seek alternative analgesic modalities., Level of Evidence: Level III, retrospective, therapeutic cohort study., (Copyright © 2021. Published by Elsevier Ltd.)

Summary: Decision-making in the treatment of proximal humerus fractures can be challenging. A careful assessment of the patient's anticipated activity and specific fracture features can help determine which treatment strategy best aligns with an individual's goals. Treatment of geriatric proximal humerus fractures is dependent on these factors and an awareness of one's own technical ability., Competing Interests: The authors report no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: We hypothesized that the modified Fragility Index (mFI), which predicts surgical complications, would be applicable to surgical complications in patients older than 50 years with distal humerus fractures (DHF)., Methods: We retrospectively reviewed the American College of Surgeons National Surgery Quality Improvement Program database, including patients older than 50 years who underwent open reduction and internal fixation of a DHF. A 5-item mFI score was calculated. Postoperative complications, readmission and reoperation rates, and length of stay were recorded. Univariate as well as a multivariable statistical analysis was performed, controlling for age, sex, body mass index, length of stay, and operative time., Results: We identified 864 patients (mean age, 68.6 years ± 10.4), and 74.1% were female. As the mFI increased from 0 to 2 or greater, 30-day readmission rate increased from 3% to 10% ( P value = .01), rate of discharge to rehabilitation facility increased from 12% to 32% ( P value = .0), and any complication rate increased from 4% to 19% ( P value = .0). Rates of pulmonary complications increased significantly in patients with the mFI of 2 or greater ( P value = .047). Patients with the mFI of 2 or greater were nearly 4 times more likely to be readmitted within 30 days (odds ratio [OR] = 3.5, P value = .007) and had an increased OR of 30-day reoperation and any complication (OR = 3.7, P value = .02; OR = 4.5, P  value = .00, respectively) on multivariate analysis., Conclusion: A fragility state is predictive of postoperative complications, readmission, and reoperation after surgical management of DHF. Our data suggest that a fragility evaluation can help inform surgical decision-making in patients older than 50 years with DHF.

Background: Medical malpractice is a very common occurrence that many medical providers will have to face; approximately 17,000 medical malpractice cases are filed in the United States each year, and more than 99% of all surgeons are faced with at least 1 instance of malpractice litigation throughout their careers. Malpractice litigation also carries a major economic weight, with medical malpractice spending resulting in an aggregate expenditure of nearly $60 billion annually in the United States. Orthopedic surgery is one of the most common subspecialties involved in malpractice claims. Currently, there are no comprehensive studies examining malpractice lawsuits within shoulder and elbow surgery. Therefore, the purpose of this work is to examine trends in malpractice claims in shoulder and elbow surgery., Methods: The Westlaw online legal database was queried in order to identify state and federal jury verdicts and settlements pertaining to shoulder and elbow surgery from 2010-2020. Only cases involving medical malpractice in which an orthopedic shoulder and elbow surgeon was a named defendant were included for analysis. All available details pertaining to the cases were collected. This included plaintiff demographic and geographic data. Details regarding the cases were also collected, such as anatomic location, pathology, complications, and case outcomes., Results: Twenty-five malpractice lawsuits pertaining to orthopedic shoulder and elbow surgery were identified. Most plaintiffs in these cases were adult men, and the majority of cases were filed in the Southwest (28%) and Midwest (28%) regions of the United States. The most common anatomic region involved in claims was the rotator cuff (32%), followed by the glenohumeral joint (20%). The majority of these claims involved surgery (56%). Pain of mechanical nature was the most common complication seen in claims (56%). The jury ruled in favor of the defendant surgeon in most cases (80%)., Discussion: This is the first study that comprehensively examines the full scope of orthopedic shoulder and elbow malpractice claims across the United States. The most common complaint that plaintiffs reported at the time of litigation was residual pain after treatment due to a mechanical etiology, followed by complaints of nerve damage. A large portion of claims resulted after nonoperative treatment. A better understanding of the trends within malpractice claims is crucial to developing strategies for prevention., (Copyright © 2021 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Introduction: Opioid sparing protocols should be formulated with appropriate demand. Specific fracture location has been hypothesized as an important predictor of post-operative pain. The purpose of this study is to evaluate the impact of fracture location on perioperative opioid demand after surgery with the hypothesis that this factor would be significantly associated with perioperative opioid demand in upper extremity fracture surgery., Methods: A national database was used to identify1-month pre-operative to 1-year postdischarge opioid demand in oxycodone 5-mg equivalents in 336,493 patients undergoing fracture fixation of the clavicle through distal radius between 2010 and 2020. Three timeframes were evaluated: 1-month pre-op to 90-days post-discharge, 3 months post-discharge to 1-year post-discharge, and 1-month pre-op to 1-year postdischarge. Multivariable main effects linear and logistic regression models were constructed to evaluate the changes in opioids filled, opioid prescriptions, and odds of two or more opioid prescriptions in these timeframes based on fracture location with adjustment for age, sex, obesity, pre-operative opioid usage, and polytrauma., Results: Compared to distal radius fracture fixation, fixation of elbow, distal humerus, humeral shaft, and proximal humerus fractures were associated with large, significant increases in 1-month pre-op to 1-year post-discharge opioid filling (33.5 - 63.4 additional oxycodone 5-mg equivalents, all p<0.05) and number of filled prescriptions (0.33 - 0.92 additional prescriptions, all p<0.05) compared to patients with other operatively treated upper extremity injuries., Discussion: Fracture location was a significant predictor of perioperative opioid demand. Elbow, distal humerus, humeral shaft, and proximal humerus fracture fixation was associated with the largest increases in opioid demand after upper extremity fracture fixation. Patients with these injuries may be at highest risk of extensive opioid consumption., Level of Evidence: Level III, retrospective, observational cohort study., Competing Interests: Declaration of competing interest Authors report no conflicts of interest., (Copyright © 2021. Published by Elsevier Ltd.)

Introduction: Perioperative opioid pain management protocols should reflect anticipated patient need. Fracture location and external fixation may be related to post-operative pain. The purpose of this study is to evaluate the impact of fracture location, articular injury, and pre-operative external fixation, and articular injury on perioperative opioid demand following definitive fixation., Methods: 1-month pre-operative to 1-year post-discharge opioid demand in oxycodone 5-mg equivalents in 23,441 patients undergoing fracture fixation of the femoral shaft through ankle between 2007 and 2017 was evaluated using a national database. Opioid demand was compiled over several timeframes: 1-month pre-op to 90-days post-discharge, 3 months post-discharge to 1-year post-discharge, and 1-month pre-op to 1-year post-discharge. Multivariable main effects linear and logistic regression models were constructed to evaluate the increased opioids filled, increased opioid prescriptions, and odds of refills in these timeframes with adjustment for fracture location, external fixator placement, and baseline patient and injury characteristics., Results: Lower extremity anatomic location and pre-operative external fixation were significantly associated with increased 1-month pre-op to 1-year post-discharge opioid filling (17.6-54.7 additional oxycodone 5-mg equivalents, all p<0.05) and number of filled prescriptions (0.28-0.54 additional prescriptions, all p<0.05). Pilon fractures and pre-operative external fixation, specifically, were associated with increased odds of two or more opioid prescriptions within the 1-month pre-op to 1-year post-discharge time frame (1.25-1.32 odds ratio, all p<0.05)., Discussion: Fracture location and pre-operative external fixator placement predicted perioperative opioid demand. Articular zone (pilon, plateau, and distal femur) fracture fixation was associated with the largest increases in opioid demand after lower extremity fracture fixation. Patients with these injuries may be at highest risk of extensive opioid consumption., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

This study evaluates the efficacy of North Carolina's Strengthen Opioid Misuse Prevention (STOP) Act in reducing the volume and rate of 90-day perioperative opioid prescribing to patients ages 18 and older after orthopaedic trauma surgery. Patients undergoing fracture surgery from January 2017 to June 2017 (pre-STOP) were compared with patients undergoing fracture surgery from January 2018 to June 2018 (post-STOP). Adjusted analyses demonstrated that patients undergoing surgery after the STOP Act (n = 730) were prescribed significantly lower volume of opioids in the discharge to 2-week time frame and at the first postoperative prescription (7.3 and 5.8 fewer oxycodone, respectively). Otherwise, there were no significant differences between the two cohorts in adjusted volume or rates of 90-day opioid prescribing. The STOP act has had only a minor impact on early post-discharge opioid prescribing in patients undergoing fracture surgery. These findings question the efficacy of this type of legislation in combating opioid overprescribing in orthopaedic trauma. (Journal of Surgical Orthopaedic Advances 30(2):101-107, 2021).

Objectives: To describe the perioperative opioid demand in a large population of patients undergoing lower extremity fracture fixation and to evaluate mental disorders such as substance abuse as risk factors for increased use., Design: Retrospective, observational., Setting: National insurance claims database., Patients/participants: Twenty-three four hundred forty-one patients grouped by mental disorders such as depression, psychoses, alcohol abuse, tobacco abuse, drug abuse, and preoperative opioid filling undergoing operative treatment of lower extremity fractures (femoral shaft through ankle) between 2007 and 2017., Intervention: Operative treatment of lower extremity fractures., Main Outcome Measures: The primary outcome was filled opioid prescription volume converted to oxycodone 5-mg pill equivalents. Secondary outcomes included the number of filled prescriptions and the risk of obtaining 2 or more opioid prescriptions., Results: Of 23,441 patients, 16,618 (70.9%), 8862 (37.8%), and 18,084 (77.1%) filled opioid prescriptions within 1-month preop to 90-day postop, 3-month postop to 1-year postop, and 1-month preop to 1-year postop, respectively. On average, patients filled 104, 69, and 173 oxycodone 5-mg pills at those time intervals. Alcohol, tobacco, drug abuse, and preoperative opioid filling were associated with increased perioperative opioid demand. Psychoses had a small effect on opioid demand, and depression had no significant impact., Conclusions: This study reports the rate and volume of opioid prescription filling in patients undergoing lower extremity fracture surgery. Substance use and abuse were the main risk factors for increased perioperative opioid prescription filling. Providers should recognize these risk factors for increased use and be judicious when prescribing opioids. Enhanced patient education, increased nonopioid pain management strategies, and referral for substance use and abuse treatment may be helpful for these patients., Level of Evidence: Level III. See Instructions for Authors for a complete description of levels of evidence., Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Antegrade humeral intramedullary nails are an effective fixation method for certain proximal humeral fractures and humeral shaft fractures. However, owing to potential rotator cuff damage during nail insertion, shoulder pain remains a common postoperative complaint. The purpose of this study was to provide quantitative data characterizing the anatomic and radiographic location of the rotator interval (RI) for an antegrade humeral intramedullary nail using a mini-deltopectoral approach., Methods: Six consecutive fresh-frozen intact cadaveric specimens (mean age, 69 ± 12.8 years) were obtained for our study. Demographic data were collected on each specimen. A mini-deltopectoral approach was used, followed by placement of a guidewire in the RI. Quantitative anatomic relationships were calculated using a fractional carbon fiber digital caliper. Radiographic measurements were performed by 2 orthopedic residents and 1 practicing fellowship-trained orthopedic surgeon. In addition to re-measurement of similar anatomic relationships on radiographs, the ratio of the distance from the lateral humeral edge to the starting point relative to the width of the humeral head on the anteroposterior (AP) view was calculated. Similarly, on the lateral view, the ratio of the distance from the anterior humeral edge to the starting point relative to the humeral head width was calculated., Results: In all cases, the described approach allowed for preservation of the biceps tendon and access to the RI for guidewire insertion, with no subsequent rotator cuff or humeral articular cartilage damage identified following nail insertion. The ratio of the distance from the lateral humeral edge to the starting point relative to the humeral head width on the AP view was 0.4 ± 0.0. The ratio of the distance from the anterior humeral edge to the starting point relative to the humeral head width on the lateral view was 0.3 ± 0.0., Conclusion: This study demonstrates the clinical feasibility of a mini-deltopectoral approach and shows that the ideal starting point through the RI radiographically lies along the medial aspect of the lateral third of the humeral head on the AP view and along the posterior aspect of the anterior third of the humeral head on the lateral view., (Copyright © 2020 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Introduction: Mental health and substance use and abuse disorders have been associated with poor patient-reported outcomes. Despite the prevalence of hip fractures in the United States, the relationship between opioid demand and these factors in hip fracture surgery is not well understood. The purpose of this study is to describe opioid filling volume and rates after hip fracture surgery and to identify mental health risk factors for increased demand. The study hypothesis is that psychiatric comorbidities such as depression and psychoses as well as substance use and abuse indicators such as pre-op opioid dependence, drug, alcohol, and tobacco abuse would be associated with increased perioperative opioid demand., Methods: This is a retrospective cohort study of 40,514 patients undergoing surgical fixation of hip fractures using a commercially available insurance database. The primary patient-level outcome was filled opioid prescription volume in oral morphine milliequivalents converted to oxycodone 5-mg equivalents up to 1-year post-op. Adjusted measures of overall quantities filled and refill rates were assessed with multivariable main effects linear and logistic regression models., Results: Twenty four thousand four hundred forty-one of 40,514 patients (60.3%) filled opioid prescriptions within 7 days pre-op to 1-year post-op. Patients filling prescriptions filled a mean of 187.7 oxycodone 5-mg equivalents. Sixteen thousand five hundred seventy-seven patients (41.1%) filled two or more opioid prescriptions within 7 days pre-op to 1-year post-op. Fifteen thousand two hundred seventy-nine patients (37.7%) filled an opioid prescription between 3 months post-op and 1-year post-op, and 8,502 patients (21%) filled an opioid prescription between 9 months post-op and 1-year post-op. In multivariable models, age, pre-op opioid filling, depression, tobacco abuse, and drug abuse were risk factors significantly associated with increased perioperative opioid filling. Psychoses had a mixed effect on outcomes with decreased early perioperative filling and increased late perioperative filling. Pre-op opioid filling had the largest impact on perioperative opioid demand., Discussion: Pre-op opioid filling and drug abuse were the main mental health-related drivers of increased perioperative opioid prescription filling. Depression, psychoses, alcohol abuse, and tobacco abuse had small effects on prescription filling. These results can help identify patients at risk for increased opioid demand who may benefit from additional counseling, maximizing alternative pain management strategies, and possible referral to pain management specialists., Level of Evidence: Level III, retrospective, prognostic cohort study., (Copyright © 2021 by the American Academy of Orthopaedic Surgeons.)

Objective: A meta-analysis and systematic review was performed to compare outcomes of open reduction and internal fixation (ORIF), hemiarthroplasty (HA), and reverse total shoulder arthroplasty (rTSA) for complex proximal humerus fractures. Data sources: MEDLINE, Embase, and Cochrane Library databases were screened. Search terms included reverse total shoulder arthroplasty, open reduction internal fixation, hemiarthroplasty, and proximal humerus fracture., Study Selection: English-language studies published within the past 15 years evaluating outcomes of ORIF, rTSA, or HA for complex proximal humerus fractures with minimum of 1-year follow-up were included, resulting in 51 studies with 3064 total patients. Review articles, basic science studies, biomechanical studies, and cadaveric studies were excluded., Data Extraction: The methodological quality of evidence was assessed using the Jadad scale and methodological index for nonrandomized studies., Data Synthesis: Demographic data were compared using the χ2 test. Mean data were weighted by study size and used to calculate composite mean values and confidence intervals. Continuous data were compared using the Metan module with fixed effects. Count data were compared using the Kruskal-Wallis test. Alpha was set at 0.05 for all tests., Conclusions: Patients undergoing rTSA had lower risks of complication (relative risk 0.41) and reoperation (relative risk 0.28) than HA patients. rTSA resulted in higher Constant scores (standard mean difference 0.63) and improved active forward flexion when compared with HA (standard mean difference 0.76). Pooled mean data demonstrated better outcome scores and active forward flexion of ORIF versus HA and rTSA, although the patients were younger and had more simple fracture patterns., Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: F. A. Liporace is a paid consultant of Wright Medical Group and receives IP royalties related to a proximal humerus locking plate. The remaining authors report no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Patients undergoing upper extremity fracture surgery often have postoperative pain that can be mitigated with opioid pain medications. Opioid misuse and abuse are growing concerns regarding the liberal use of opioids in the perioperative setting. The impact of mental health disorders and substance abuse on perioperative opioid demand is largely unknown. The purpose of this study is to describe perioperative opioid filling and risk factors for increased filling after upper extremity fractures. The study hypothesis is that poor mental health and substance abuse will be associated with increased opioid demand., Methods: This is a retrospective, cohort study of 26,283 patients undergoing operative fixation of upper extremity fractures involving the proximal humerus through distal radius using a commercially available insurance database. Opioid prescription filling in oxycodone 5-mg equivalents and refills were tabulated from 1 month preoperation to 1 year postoperation. Multivariable linear and logistic regression models were constructed in R (Statistical Analysis Software) to evaluate associations between mental health and substance use disorders and opioid-related outcomes with adjustment for baseline patient and treatment factors such as age, sex, comorbidities, and fracture location., Results: Of the 26,283 patients in the cohort, 79.9%, 32.6%, and 83.1% filled at least 1 opioid prescription in the 1-month preoperative to 90-day postoperative, 3-month postoperative to 1-year postoperative, and 1-month preoperative to 1-year postoperative time frames, respectively. Mean opioid volume prescribed during those time frames was 103.7, 53.5, and 156.9 oxycodone 5-mg equivalents, respectively. Drug abuse, psychoses, and preoperative opioid filling were significant mental health-related drivers of increased postoperative opioid demand., Discussion: This study reports the rate and volume of opioid prescription filling in patients undergoing upper extremity fracture surgery. Mental health and substance use disorders were significant drivers of perioperative opioid demand. These study findings can guide surgeons to anticipate expected perioperative opioid demand and identify patients who may benefit from collaboration with pain management specialists during the perioperative period., (Copyright © 2020 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

After-hours surgery represents a novel solution that can effectively combat surgical fatigue of care teams in addition to addressing the high volume of surgical backlog associated with the repercussions of the COVID-19 pandemic. This commentary seeks to rationalize how successful employment of a dedicated after-hours surgical team and protocol has tremendous potential for increased efficiency while maintaining good surgical outcomes in patients., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Open tibia fractures are often associated with considerable soft tissue injuries. Management of open tibia fractures can be challenging, and some patients require amputation. The patient and treatment factors have not been described on a population level in the United States. A retrospective analysis was completed using the 2000 to 2011 Nationwide Inpatient Sample. Amputation rates during the index hospitalization after open tibia fracture were computed based on injury, patient, and hospital characteristics in patients 18 years or older. The overall amputation rate in open tibia fractures during the index hospitalization was 2.2% (n=3769). Patients with midshaft tibia fractures comprised the largest portion of patients undergoing amputation (46.8% of total amputations) compared with distal tibia (34.0%) and proximal tibia (19.3%) fractures. Patients with no neurovascular injury comprised the largest portion of patients undergoing amputation (85.9%), followed by isolated arterial injury (11.1%), combined neurovascular injury (1.9%), and isolated nerve injury (1.1%). Amputation rates were significantly increased for midshaft tibia fractures with neurovascular injury (odds ratio, 12.39; 95% CI, 5.52-27.83) and distal tibia fractures with neurovascular injury (odds ratio, 5.45; 95% CI, 1.73-17.19) compared with tibia fractures with no neurovascular injury while controlling for confounders. On the basis of a review of the Nationwide In-patient Sample during the past decade, the authors have shown that the early amputation rate in open tibia fractures for all-comers is 2.2%. Rates of amputation varied based on fracture site, associated neurovascular injury, medical comorbidities, and hospital location. [Orthopedics. 2021;44(1):48-53.]., (Copyright 2020, SLACK Incorporated.)

Objective: We sought to determine the flammability of the skin at different time intervals after chlorhexidine-alcohol antiseptic scrub application, to provide evidence for hospital protocols recommending a 3-minute drying time., Methods: Swine feet, which contain the skin, subcutaneous tissue, muscle, and bone, were used for an experimental cohort. The skin was prepped with chlorhexidine-alcohol solution. Attempted ignition with an open flame was then performed in the presence of visible pooling, as well as at time points 0, 30, 60, and 90 seconds after application, in addition to when the skin appeared visibly dry. Six samples were used for each time point tested., Results: At time 0 seconds and with gross pooling, ignition was achieved with all samples tested. However, at 30 seconds, only 2 of 6 samples were ignited (which appeared wet). No samples after 60 or 90 seconds were flammable. Samples appeared dry after an average of 40.5 seconds and were not able to ignite., Conclusions: Although our findings do support that a chlorhexidine-alcohol antiseptic scrub is a potentially flammable surgical prep solution, we found little support for a 3-minute time cutoff. More importantly, the presence of pooling and persistently wet appearing prep is a more important fire risk than the time elapsed after prep application. Caution should be used when working with any flammable solution, and efforts to minimize chemical burns and combustion should be sought based on evidence., Competing Interests: The authors report no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)