Keli Doe

Abstract Triple negative breast cancer (TNBC) has an unusually low 5-year survival rate linked to higher metastatic rates. Our laboratory recently delineated a role for the alternative RNA splicing (AS) of cytoplasmic polyadenylation element binding protein 2 (CPEB2), via inclusion/exclusion of exon 4, in the metastasis of TNBC. In these studies, the mechanism governing the inclusion/exclusion of exon 4 was examined. Specifically, the RNA trans-factor, SRSF3, was found to be explicitly associated with CPEB2 exon 4. A SRSF3 consensus sequence was identified in exon 4, and mutation of this sequence abolished the association of SRSF3. The expression of SRSF3 was upregulated in TNBC cells upon the acquisition of anoikis resistance correlating with a reduction in the CPEB2A/B ratio. Importantly, downregulation of SRSF3 in these cells by siRNA induced the exclusion of exon 4 in cells increasing the ratio of CPEB2A (exon 4 excluded) to CPEB2B (exon 4 included). Downregulation of SRSF3 also reversed the CPEB2A/B ratio of a wild-type CPEB2 exon 4 minigene and endogenous CPEB2 pre-mRNA, but not a mutant CPEB2 minigene with the SRSF3 RNA cis-element ablated. SRSF3 downregulation ablated the anoikis resistance of TNBC cells, which was “rescued” by ectopic expression of CPEB2B. Finally, analysis of The Cancer Genome Atlas database showed a positive relationship between SRSF3 expression and lower CPEB2A/B ratios in aggressive breast cancers. Implications: These findings demonstrate that SRSF3 modulates CPEB2 AS to induce the expression of the CPEB2B isoform that drives TNBC phenotypes correlating with aggressive human breast cancer. Visual Overview: http://mcr.aacrjournals.org/content/molcanres/17/9/1920/F1.large.jpg.

BACKGROUND: Recent literature suggests that state-level legislation is effective in reducing postoperative opioid prescribing after total joint arthroplasty but has not addressed the effect on opioid antagonist coprescribing. This study aims to describe the change in postoperative opioid and opioid antagonist prescribing patterns after total joint arthroplasty following passage of state-level opioid-limiting legislation and to determine the comorbidities associated with increased opioid prescribing in this population. METHODS: Billing data were used to identify all patients who underwent primary total hip or knee arthroplasty admitted between March 2016 and March 2018 at our institution. The data were divided into 2 cohorts comprising the year before (671 subjects) and after (713 subjects) the legislation. Discharge prescriptions were reviewed, and the median morphine milligram equivalents (MME) per day and naloxone prescriptions were recorded. International Classification of Diseases codes were used to identify comorbid conditions of interest present during previous inpatient or outpatient encounters. RESULTS: There was a significant reduction in both the minimum and maximum median MME per day after introduction of state legislation and a substantial increase in opioid antagonist coprescription. Total knee arthroplasty, younger age, male sex, chronic pain disorders, post-traumatic stress disorder, and prior opioid abuse were correlated with increased opioid prescribing. CONCLUSION: Our findings suggest that state-level legislation is effective in decreasing the MME per day prescribed and increasing opioid antagonist coprescription in the postoperative period for patients undergoing total hip and knee arthroplasties at our institution. These changes may lead to a decrease in opioid-related morbidity and mortality in the patient population undergoing total hip and knee arthroplasties.

OBJECTIVES: To compare 1-year revision rates among left-sided and right-sided intertrochanteric femur fractures. DESIGN: Retrospective. SETTING: 120+ contributing centers to multicentered database. PATIENT SELECTION CRITERIA: Patients who sustained intertrochanteric femur fracture (ITFF) and had a cephalomedullary nail (CMN) from 2015 to 2022 were identified. Patients were then stratified based on left-sided or right-sided fracture. Patients were excluded if younger than 18 years with <1-year follow-up. The intervention investigated was CMN on left or right side. OUTCOME MEASURES AND COMPARISONS: One-year revision surgery, comparing CMN performed on left or right side for ITFFs. RESULTS: In total, 113,626 patients met inclusion criteria, with 55,295 in the right-sided cohort and 58,331 in the left-sided cohort. There was no difference between cohorts with respect to age, gender, diabetes, osteoporosis, chronic kidney disease, or congestive heart failure (P > 0.05 for all). Patients who sustained a left ITFF and treated with a CMN were more likely to have revision surgery at 1 year (Left: 1.24%, Right: 0.90%; OR: 1.24; 95% confidence interval [CI], 1.15-1.1.33) or develop a nonunion or malunion (Left: 1.30%, Right: 0.98%; OR: 1.31; 95% CI, 1.14-1.52). The most common revision surgery conducted for both cohorts was conversion total hip arthroplasty (Left: 70.4% and Right: 70.0%). CONCLUSIONS: Patients who sustained a left intertrochanteric femur fracture and were treated with a CMN were more likely to undergo revision at 1 year due to nonunion. There were no differences in demographics and comorbidities between cohorts. Though left-sided versus right-sided confounding variables may exist, the difference in nonunion rate may be explained by clockwise torque of the lag screw used in most implants. Increased awareness, implant design, and improved technique during fracture reduction and fixation may help lower this disproportionate nonunion rate and its associated morbidity and financial impact. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Introduction: Surgical management of isolated acetabular fracture dislocations, femoral shaft fractures, and tibial shaft fractures are well-documented, but there is limited literature on the acute management of these injuries when they occur concomitantly in the same patient on the ipsilateral extremity. We present a case of the acute treatment of a 33-year-old patient with a right ipsilateral floating hip and knee injury secondary to a motor vehicle accident. We offer a unique surgical technique for the urgent management of this rare combined injury. Case Presentation: A 33-year-old female presented to our trauma center with an ipsilateral acute posterior wall fracture dislocation, femoral head impaction fracture, femoral shaft fracture, and tibial shaft fracture. After a failed hip reduction attempt in the emergency department, she was urgently brought to the operating room for further management. She underwent percutaneous-assisted schanz pin reduction of the hip, intramedullary nail fixation of the femur and tibia, and dynamic fluoroscopic examination of the hip under anesthesia. Conclusion: Successful management of the rare combined floating hip and knee injury requires urgent intervention. The reduction of the hip dislocation is difficult due to the associated injuries. We recommend urgent surgical intervention and the utilization of a percutaneous schanz pin in the proximal femur with gentle manipulation. In most cases, this can effectively reduce the hip without a formal open approach.

Introduction: Brown-Séquard syndrome (BSS) is a rare neurological condition characterized by hemiplegia and hemianesthesia. It occurs as the sequelae to a hemi-transection of the spinal cord, and constitutes an incomplete spinal cord injury. We report a case of presumed BSS that resulted from a stab wound to the thoracic spine. Case Report: A 64-year-old male presented to Howard University Hospital with complaints of back pain and loss of left lower extremity motor function. Neurological examination revealed weakness in the L2 through S1 nerve root distributions in the left lower extremity and hypoesthesia along the L2 through S1 dermatomal distributions in the right lower extremity. Imaging disclosed a foreign body extending from the muscle layer through the T6–T7 disc space. The patient was treated operatively with removal of a knife blade; the handle of which had been broken off at the surface of the skin. Post-operatively, prior to his discharge to an acute rehabilitation center, the patient’s motor symptoms improved while his sensory symptoms worsened. He was lost to follow-up for approximately six months and returned with a debilitating spastic paraparesis. Conclusion: The presenting symptoms of BSS are not always uniform, and thus may constitute a Brown-Séquard plus syndrome (BSPS). Surgical intervention is rare; however, it may occasionally be necessary in the setting of penetrating trauma. Long-term functional recovery for BSS as documented in the literature is variable. With aggressive physical therapy and rehabilitation, a good outcome is attainable. The functional outcome of BSPS, however, may not be as favorable.