Liposomal Bupivacaine Decreases Intravenous Opioid Use in Patients with Hip Fracture: A Modification to a Novel Pain Protocol.

INTRODUCTION: The aim of this study was to determine whether the administration of liposomal bupivacaine decreased opioid use and delirium in patients sustaining a hip fracture. METHODS: A retrospective review of patients with hip fracture from September 2018 to October 2019 was performed through our institution's hip fracture registry. A liposomal bupivacaine cocktail was administered intraoperatively. Opioid requirement was determined for postoperative days 1, 2, and 3. Delirium was identified through chart review. Visual analog scale pain scores were averaged for postoperative days 1, 2, and 3. Four groups were analyzed: patients who received liposomal bupivacaine and IV acetaminophen, patients who only received IV acetaminophen, patients who only received liposomal bupivacaine, and control patients whose data were collected before this intervention. Continuous data were compared using a one-way analysis of variance or Student t-test, as applicable. Categorical data were compared using the Fisher exact test. Significance was set at P < 0.05. RESULTS: One hundred nine patients met the inclusion criteria for the study with a mean age of 81.2 years. Eighty-two patients (75.2%) received intraoperative liposomal bupivacaine during the study year. Intravenous opioid requirement was markedly different among all four groups in all postoperative days. Oral opioid requirement and pain scores were not different between groups on any postoperative day. A notable decrease in IV opioid requirement in all postoperative days was seen in the Intervention groups (day 1 P < 0.001, day 2 P = 0.002, and day 3 P = 0.030). There existed a trend toward decreased delirium rates in the Intervention groups compared with the No Intervention group (23.9% vs. 32.8%, P = 0.272). CONCLUSION: The inclusion of liposomal bupivacaine in our institution's novel pain protocol led to notable decreases in opioid requirement in all postoperative days studied with a trend toward decreased delirium rates as well.

Objects in Mirror Are Closer Than They Appear: Symptoms of Depression and Suicidality in Orthopaedic Surgeons.

BACKGROUND: Suicide and depression among orthopaedic surgeons have recently emerged as rising concerns. Prior research has suggested that orthopaedic surgeons have the highest prevalence of suicide among surgical specialties. We sought to determine the factors associated with depression and suicidal ideation (SI) in orthopaedics, including subspecialty. METHODS: A survey including demographic questions, the Beck Depression Inventory, and the Columbia-Suicide Severity Rating Scale was administered electronically via a listserv to the orthopaedic subspecialties of trauma, adult reconstruction, hand and upper extremity, shoulder and elbow, foot and ankle, spine, pediatrics, sports medicine, and oncology. The responses were quantified according to previously published criteria. The associations of demographic factors, training, and current practice environment with depression and suicidality were assessed using Fisher exact tests. Reverse stepwise multivariable logistic regression models were developed to identify factors associated with depression and SI. RESULTS: The responses were obtained from 661 board-certified, practicing orthopaedic surgeons. In this study, 156 surgeons (23.6%) endorsed some level of active SI in their lifetime, 200 surgeons (30.3%) reported either active or passive SI in their lifetime, and 33 surgeons (5%) reported that, on at least 1 occasion in their lifetime, they had experienced active SI with a specific plan and intention to harm themselves. Gender, relationship status, having children, and residency and/or current practice region were significantly associated with depression and/or SI. Younger age, divorce, adult reconstruction and foot and ankle subspecialties, and attending residency in the Western U.S. were found on multivariable testing to be associated with symptoms of depression and SI (odds ratios, 1.03 [per 1-year decrease in age] to 8.28). CONCLUSIONS: Symptoms of depression and suicidality are not uncommon among orthopaedic surgeons, and variation by gender, relationship status, and geographic location are supported by prior research. Based on our results, depression and/or SI likely affect someone close to you or someone with whom you work. The normalization of discussions surrounding emotional well-being, depression, and SI is imperative.

Training Surgery Residents to be Leaders: Construction of a Resident Leadership Curriculum.

SUMMARY: Historically, the traditional pathways into plastic surgery required board eligibility in a surgical specialty such as general surgery, orthopedics, urology, neurosurgery, otolaryngology, or ophthalmology. This requirement resulted in plastic surgery residents who had served as chief residents before plastic surgery training. Their maturity emotionally and surgically allowed them to immediately concentrate on the new language and principles of plastic surgery. They had led others and were capable of leading themselves in a new surgical discipline. Today, medical students typically match into surgical specialties directly out of medical school and need to spend their time learning basic surgical skills and patient care because of the contracted time afforded to them. Formal leadership training has historically been limited in surgical training. The authors set out to delineate the creation, implementation, and perceptions of a leadership program within a surgical residency and provide guideposts for the development of engaged, conscious, and dedicated leaders within the residencies they lead.

Subspecialty Fellowship Training Is Not Associated With Better Outcomes in Fixation of Low-Energy Femoral Neck Fractures-An Analysis of the Fixation Using Alternative Implants for the Treatment of Hip Fractures Database.

OBJECTIVES: To compare risk of reoperation for femoral neck fracture patients undergoing fixation with cancellous screws (CSs) or sliding hip screws based on surgeon fellowship (trauma-fellowship-trained vs. non-trauma-fellowship-trained). DESIGN: Retrospective review of Fixation using Alternative Implants for the Treatment of Hip fractures data. SETTING: Eighty-one centers across 8 countries. PATIENTS/PARTICIPANTS: Eight hundred nineteen patients ≥50 years old with low-energy hip fractures requiring surgical fixation. INTERVENTION: Patients were randomized to CS or sliding hip screw group in the initial dataset. MAIN OUTCOME MEASUREMENTS: The primary outcome was risk of reoperation. Secondary outcomes included death, serious adverse events, radiographic healing, discharge disposition, and use of ambulatory devices postoperatively. RESULTS: There was no difference in risk of reoperation between the 2 surgeon groups (P > 0.05). Patients treated by orthopaedic trauma surgeons were more likely to be overweight/obese and have major medical comorbidities (P < 0.05). There was a higher risk of serious adverse events, higher likelihood of radiographic healing, and higher odds of discharge to a facility for patients treated by trauma-fellowship-trained surgeons (P < 0.05). CONCLUSIONS: Based on these data, risk of reoperation for low-energy femoral neck fracture fixation is equivalent regardless of fellowship training. The higher likelihood of radiographic healing noted in the trauma-trained group does not seem to have a major clinical implication because it did not affect risk of reoperation between the 2 groups. Patient-specific factors present preinjury, such as body habitus and medical comorbidities, may account for the lower odds of discharge to home and higher risk of postoperative medical complications for patients treated by orthopaedic trauma surgeons. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Precision Medicine in Oncology: A Review of Multi-Tumor Actionable Molecular Targets with an Emphasis on Non-Small Cell Lung Cancer.

Precision medicine is essential for the modern care of a patient with cancer. Comprehensive molecular profiling of the tumor itself is necessary to determine the presence or absence of certain targetable abnormalities or biomarkers. In particular, lung cancer is a disease for which targetable genomic alterations will soon guide therapy in the majority of cases. In this comprehensive review of solid tumor-based biomarkers, we describe the genomic alterations for which targeted agents have been approved by the United States Food and Drug Administration (FDA). While focusing on alterations leading to approvals in a tumor-agnostic fashion (MSI-h, TMB-h, NTRK) and on those alterations with approvals in multiple malignancies (BRAF, ERBB2, RET, BRCA, PD-L1), we also describe several biomarkers or indications that are likely to lead to an approved drug in the near future (e.g., KRAS G12C, PD-L1 amplification, HER2 overexpression in colon cancer, HER2 mutations in lung cancer). Finally, we detail the current landscape of additional actionable alterations (EGFR, ALK, ROS1, MET) in lung cancer, a biomarker-rich malignancy that has greatly benefitted from the precision oncology revolution.

COVID-19 as a disruptor: innovation and value in a national virtual fracture conference.

OBJECTIVES: The aim of this study was to determine the educational value of a national virtual fracture conference implemented during the COVID-19 disruption of resident education. DESIGN: Survey study. SETTING: National virtual conference administered by the Orthopaedic Trauma Association. PARTICIPANTS: Attendees of virtual fracture conference. INTERVENTION: Participation at a national virtual fracture conference. MAIN OUTCOME MEASURE: Surveys of perception of quality and value of virtual conferences relative to in-person conferences. RESULTS: Ninety-six percent of participants rated the virtual fracture conference as similar or improved educational quality relative to conventional in-person fracture conference. Participants also felt they learned as much (35%) or more (57%) at each virtual fracture conference compared to the amount learned in-person. The quality of interpersonal interactions at both the resident-faculty level and faculty-faculty level was also perceived to be overall superior to those at participants' own institutions. Learners felt they were more likely to engage the primary literature as well. Overall, 100% of participants were likely to recommend virtual conference to their colleagues and 100% recommended continuing this conference even after COVID-19 issues resolve. CONCLUSIONS: We found that learners find significant educational value in a national virtual fracture conference compared to in-person fracture conferences at their own institution. COVID-19 has proven to be a disruptor not only in health care but in medical education as well, accelerating our adoption of innovative and novel resident didactics. LEVEL OF EVIDENCE: Therapeutic Level III.

Increasing Reoperations and Failures With Increasing BMI in Patients Undergoing 2-Stage Exchange for Infected Total Hip Arthroplasty.

BACKGROUND: While morbid obesity is associated with increased infection after total hip arthroplasty, little is known on the outcomes after 2-stage reimplantation for prosthetic joint infection (PJI) in this population. The purpose of this study is to evaluate the impact of morbid obesity (body mass index>40 kg/m2) on reinfection, postoperative complications, readmissions, and reoperations. METHODS: We conducted a retrospective review of 107 patients undergoing first time 2-stage reimplantation for PJI from 2013 to 2019. 18 patients (50% women) with body mass index>40 kg/m2 were identified. To minimize confounders, three propensity score matched cohorts were created, yielding 16 nonobese (<30 kg/m2), 16 obese (30-39.9 kg/m2), and 18 morbidly obese (>40 kg/m2) patients. Outcomes were compared using chi-square or Fisher's exact tests. All patients had minimum 12-month follow-up, with mean follow-up of 36.3, 30.1, and 40.0 months in the nonobese, obese, and morbidly obese cohorts, respectively. RESULTS: Compared with nonobese patients, morbidly obese patients had a higher rate of reinfection (0% vs 33%, P = .020 and higher likelihood of length of stay>4 days (19% vs 61%, P = .012). In addition, compared with nonobese and obese patients, morbidly obese patients had higher rate of return to the operating room for any reason (13% vs 19% vs 50%, respectively, P = .020). No differences between cohorts were found regarding complications, death, or revision surgery. CONCLUSION: Morbidly obese patients have significantly increased risk of reinfection and reoperation after 2-stage reimplantation for PJI when compared with obese and nonobese patients. These data can be used to counsel morbidly obese patients contemplating total hip arthroplasty and supports the notion of deferring arthroplasty in this population pending optimization.

Prevalence of class I-III BRAF mutations among 114,662 cancer patients in a large genomic database.

IMPACT STATEMENT: These data represent the largest aggregation of BRAF mutations within a single clinical database to our knowledge. The relative proportions of both BRAF V600 mutations and non-V600 mutations are informative in all cancers and by malignancy, and can serve as a definitive gold-standard for BRAF mutation cancer incidence by malignancy. The rate of BRAF mutation in human cancer in a real-world large database is lower than previously reported likely representing testing more broadly across tumor types. The relative percentages of Class II and Class III BRAF mutations are higher than previously reported, representing almost 35% of BRAF mutations in cancer. These findings provide support for the development of effective treatments for non-V600 BRAF mutations in cancer.

Who Did the Arthroplasty? Hip Fracture Surgery Reoperation Rates are Not Affected by Type of Training-An Analysis of the HEALTH Database.

OBJECTIVES: This study compares outcomes for patients with displaced femoral neck fractures undergoing hemiarthroplasty (HA) or total hip arthroplasty (THA) by surgeons of different fellowship training. DESIGN: Retrospective review of HEALTH trial data. SETTING: Eighty clinical sites across 10 countries. PATIENTS/PARTICIPANTS: One thousand four hundred forty-one patients ≥50 years with low-energy hip fractures requiring surgical intervention. INTERVENTION: Patients were randomized to either HA or THA groups in the initial data set. Surgeons' fellowship training was ascertained retrospectively, and outcomes were compared. MAIN OUTCOME MEASUREMENTS: The main outcome was an unplanned secondary procedure at 24 months. Secondary outcomes included death, serious adverse events, prosthetic joint infection (PJI), dislocation, discharge disposition, and use of ambulatory devices postoperatively. RESULTS: There was a significantly higher risk of PJI in patients treated by surgeons without fellowship training in arthroplasty (P = 0.01), surgeons with unknown fellowship training (P = 0.03), and surgeons with no fellowship training (P = 0.02) than those treated by an arthroplasty-trained surgeon. There were significantly higher odds of being discharged to a facility rather than home in patients who underwent surgery by a surgeon with no fellowship training compared with arthroplasty-fellowship-trained surgeons (P = 0.03). CONCLUSIONS: Arthroplasty for hip fracture can be performed by all orthopaedic surgeons with equivalent reoperation rates. Infection prevention strategies and use of "care pathways" by arthroplasty-fellowship-trained surgeons may account for the lower risk of PJI and higher rate of discharge to home. The authors advocate for the use of evidence-based infection prevention initiatives and standardized care pathways in this patient population. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Prevalence of Lymphoid Neoplasia in a Retrospective Analysis of Warthin Tumor: A Single Institution Experience.

Warthin tumor is one of the most common benign salivary gland tumors. Overt lymphoma is known to occur in the lymphoid stroma of Warthin tumor. In situ follicular neoplasia is difficult to identify in routine histologic examination of lymphoid tissue and has not been reported in association with Warthin tumor. Our objective is to determine the prevalence of overt malignant lymphoma and in situ follicular neoplasia in Warthin tumor. We conducted a retrospective histological evaluation of 89 sequential Warthin tumor cases with available slides and blocks from the years 2010-2019. Of these, 84 cases were subjected to immunohistochemical testing, while 5 cases had been previously worked up for the suspicion of lymphoma. We identified two additional cases of lymphoid neoplasia associated with Warthin tumor including small lymphocytic lymphoma/chronic lymphocytic leukemia (n = 1) and in situ follicular neoplasia (n = 1) in addition to previously reported case of follicular lymphoma included in this study. The prevalence rate of first-time detected lymphoid neoplasia in Warthin tumor is 3.4%. The prevalence rate of overt lymphoma is 2.2%, while the prevalence of in situ follicular neoplasia is 1.1%. We propose histologic criteria to identify small lymphocytic lymphoma and follicular lymphoma in Warthin tumor. These include a monotonous interfollicular expansion of small lymphocytes and germinal centers composed of a monotonous population of lymphocytes without polarity or tingible body macrophages respectively. It is very important for pathologists to perform a diligent morphological examination and perform immunohistochemistry in suspected cases to identify subtle involvement of Warthin tumor by lymphoma. In patients with involvement of Warthin tumor by in situ follicular neoplasia, concurrent lymphoma in the same tissue and other sites should be considered. Patients without overt lymphoma elsewhere likely have a low risk of progression to follicular lymphoma. The low prevalence of in situ follicular neoplasia in Warthin tumor, combined with the low rate of clinical progression to lymphoma, make routine screening of Warthin tumor for in situ follicular neoplasia unnecessary.

Comprehensive tumor profiling reveals unique molecular differences between peritoneal metastases and primary colorectal adenocarcinoma.

BACKGROUND AND OBJECTIVES: Peritoneal metastases (PM) from primary colorectal cancer (pCRC) are associated with poor outcomes; however, molecular differences are not well defined. METHODS: We compared unpaired tumor profiles of patients with pCRC and PM from Caris Life Sciences. Testing included next-generation sequencing of 592 genes, microsatellite instability (MSI) and tumor mutational burden (TMB). Mutations were test-defined as pathogenic (PATH). RESULTS: Six hundred seventeen pCRC and 348 PM patients had similar gender (55% male) and age (median 59). PATHs were similar between PM and pCRC in KRAS, BRAF, SMAD2, SMAD4, and PTEN. pCRC PATHs were increased in APC (76% vs 48%, P < .01), ARID1A (29% vs 12%, P < .05), TP53 (72% vs 53%, P < .01), PIK3CA (22% vs 15%, P < .05), and FBXW7 (13% vs 7%, P < .01) compared with PM. Mucinous PM had more PATHs in GNAS (19% vs 8%, P = .032) while nonmucinous PM had more PATHs in BRAF (13% vs 8%, P = .027). Right-sided PM had decreased PATHs in APC (39% vs 68%, P < .0001), ARID1A (7% vs 38%, P < .004), and TP53 (48% vs 65%, P = .033) while there were no difference for left-sided PM. Nine percent of pCRC and 6% of PM were MSI-high (P = NS). There was no difference in TMB-high, TMB-intermediate, or TMB-low between PM and pCRC. CONCLUSIONS: PM have similar rates of KRAS mutation with increased PATHs in GNAS (mucinous) and BRAF (nonmucinous) compared to pCRC. No differences in MSI or TMB were identified between PM and pCRC tumors. These findings inform future study into the molecular profile of PM.

Follicular Lymphoma Diagnosed in Warthin Tumor: A Case Report and Review of the Literature.

Warthin tumor is one of the most common benign salivary gland tumors. It is unusual and difficult to diagnose follicular lymphoma within the lymphoid tissue of Warthin tumor. We present a rare case of a 69-year-old man with systemic follicular lymphoma initially diagnosed in a Warthin tumor. Lymphomas occurring within Warthin tumors are rare, however, follicular lymphoma is most commonly reported. Because these patients require further treatment depending on the stage of a disease, it is important for a pathologist to review the histology of Warthin tumors diligently to identify occult lymphomas.

Variation Among Pediatric Orthopaedic Surgeons When Diagnosing and Treating Pediatric and Adolescent Distal Radius Fractures.

BACKGROUND: Distal radius fractures are the most common injury in the pediatric population. The purpose of this study was to determine the variation among pediatric orthopaedic surgeons when diagnosing and treating distal radius fractures. METHODS: Nine pediatric orthopaedic surgeons reviewed 100 sets of wrist radiographs and were asked to describe the fracture, prescribe the type of treatment and length of immobilization, and determine the next follow-up visit. κ statistics were performed to assess the agreement with the chance agreement removed. RESULTS: Only fair agreement was present when diagnosing and classifying the distal radius fractures (κ=0.379). There was poor agreement regarding the type of treatment that would be recommended (κ=0.059). There was no agreement regarding the length of immobilization (κ=-0.004).Poor agreement was also present regarding when the first follow-up visit should occur (κ=0.088), whether or not new radiographs should be obtained at the first follow-up visit (κ=0.133), and if radiographs were necessary at the final follow-up visit (κ=0.163). Surgeons had fair agreement regarding stability of the fracture (κ=0.320).A subgroup analysis comparing various traits of the treatment immobilization showed providers only had a slight level of agreement on whether splint or cast immobilization should be used (κ=0.072). There was poor agreement regarding whether long-arm or short-arm immobilization should be prescribed (κ=-0.067).Twenty-three of the 100 radiographs were diagnosed as a torus/buckle fracture by all 9 surgeons. κ analysis performed on all the treatment and management questions showed that each query had poor agreement. CONCLUSIONS: The interobserver reliability of diagnosing pediatric distal radius fractures showed only fair agreement. This study demonstrates that there is no standardization regarding how to treat these fractures and the length of immobilization required for proper fracture healing. Better classification systems of distal radius fractures are needed that standardize the treatment of these injuries. LEVEL OF EVIDENCE: Level II.

Tumor Mutational Burden Is Site Specific in Non-Small-Cell Lung Cancer and Is Highest in Lung Adenocarcinoma Brain Metastases.

PURPOSE: Tumor mutational burden (TMB) is a developing biomarker in non-small-cell lung cancer (NSCLC). Little is known regarding differences between TMB and sample location, histology, or other biomarkers. METHODS: A total of 3,424 unmatched NSCLC samples, including 2,351 lung adenocarcinomas (LUADs) and 1,073 lung squamous cell carcinomas (LUSCs), underwent profiling, including next-generation sequencing of 592 cancer-related genes, programmed death ligand 1 immunohistochemistry, and TMB. The rate TMB of 10 mutations per megabase (Mb) or greater was compared between primary and metastatic LUAD and LUSC. Molecular alteration frequency was compared at a cutoff of 10 mutations/Mb. RESULTS: LUAD metastases were more likely to have a TMB of 10 mutations/Mb or greater compared with primary LUADs (38% v 25%; P < .001), and this difference was most pronounced with brain metastases (61% v 35% for other metastases; P < .001). The median TMB for LUAD brain metastases was 13 mutations/Mb compared with six mutations/Mb for primary LUADs. Variability existed for other LUAD metastasis sites, with adrenal metastases most likely to meet the cutoff of 10 mutations/Mb (51%) and bone metastases least likely to meet the cutoff (19%). TMB was more commonly 10 mutations/Mb or greater for LUSC primary tumors than for LUAD primary tumors (35% v 25%, respectively; P < .001). LUSC metastases were more likely to have a TMB of 10 mutations/Mb or greater than LUSC primary tumors. Poorly differentiated disease was more likely have a TMB of 10 mutations/Mb or greater when stratified by histology and primary tumor or metastasis. Site-specific molecular differences existed at this TMB cutoff including programmed death ligand 1 positivity and STK11 and KRAS mutation rate. CONCLUSION: TMB is a site-specific biomarker in NSCLC with important spatial and histologic differences. TMB is more frequently 10 mutations/Mb or greater in LUAD and LUSC metastases and highest in LUAD brain metastases. Along this TMB cutoff, clinically informative distinctions exist in other tumor profiling characteristics. Further investigation is needed to expand on these findings.

Improved Tumor Purity Metrics in Next-generation Sequencing for Clinical Practice: The Integrated Interpretation of Neoplastic Cellularity and Sequencing Results (IINCaSe) Approach.

Neoplastic cellularity contributes to the analytic sensitivity of most present technologies for mutation detection, such that they underperform when stroma and inflammatory cells dilute a cancer specimen's variant fraction. Thus, tumor purity assessment by light microscopy is used to determine sample adequacy before sequencing and to interpret the significance of negative results and mutant allele fraction afterwards. However, pathologist estimates of tumor purity are imprecise and have limited reproducibility. With the advent of massively parallel sequencing, large amounts of molecular data can be analyzed by computational purity algorithms. We retrospectively compared tumor purity of 3 computational algorithms with neoplastic cellularity using hematoxylin and eosin light microscopy to determine which was best for clinical evaluation of molecular profiling. Data were analyzed from 881 cancer patients from a clinical trial cohort, LCCC1108 (UNCseq), whose tumors had targeted massively parallel sequencing. Concordance among algorithms was poor, and the specimens analyzed had high rates of algorithm failure partially due to variable tumor purity. Computational tumor purity estimates did not add value beyond the pathologist's estimate of neoplastic cellularity microscopy. To improve present methods, we propose a semiquantitative, clinically applicable strategy based on mutant allele fraction and copy number changes present within a given specimen, which when combined with the morphologic tumor purity estimate, guide the interpretation of next-generation sequencing results in cancer patients.

Correction to: Genomic landscape of small cell carcinoma of the breast contrasted to small cell carcinoma of the lung.

In the original publication, the sixth author name was published incorrectly as Matthew Stein. The correct author name should read as Matthew K Stein.