Protein phosphatase 2A Aα regulates Aß protein expression and stability.

Protein phosphatase 2A (PP2A) represses many oncogenic signaling pathways and is an important tumor suppressor. PP2A comprises three distinct subunits and forms through a highly regulated biogenesis process, with the scaffolding A subunit existing as two highly related isoforms, Aα and Aß. PP2A's tumor-suppressive functions have been intensely studied, and PP2A inactivation has been shown to be a prerequisite for tumor formation. Interestingly, although partial loss of the Aα isoform is growth promoting, complete Aα loss has no transformative properties. Additionally, in cancer patients, Aα is found to be inactivated in a haploinsufficient manner. Using both cellular and in vivo systems, colorectal and endometrial cancer cell lines, and biochemical and cellular assays, here we examined why the complete loss of Aα does not promote tumorigenesis. CRISPR/Cas9-mediated homozygous Aα deletion resulted in decreased colony formation and tumor growth across multiple cell lines. Protein expression analysis of PP2A family members revealed that the Aα deletion markedly up-regulates Aß protein expression by increasing Aß protein stability. Aß knockdown in control and Aα knockout cell lines indicated that Aß is necessary for cell survival in the Aα knockout cells. In the setting of Aα deficiency, co-immunoprecipitation analysis revealed increased binding of specific PP2A regulatory subunits to Aß, and knockdown of these regulatory subunits restored colony-forming ability. Taken together, our results uncover a mechanism by which PP2A Aα regulates Aß protein stability and activity and suggests why homozygous loss of Aα is rarely seen in cancer patients.

Fractures in Patients With Diabetes Mellitus: Findings From a 20-year Registry at a Single Level 1 Trauma Center.

INTRODUCTION: Diabetes mellitus (DM) is a risk factor of infection. Although DM has been associated with worse functional outcomes after acetabular fracture, literature regarding the effect of DM on surgical site infection and other early complications is lacking. METHODS: A 20-year registry from a level 1 trauma center was queried to identify 134 patients with DM and 345 nondiabetic patients with acetabular fractures. RESULTS: The diabetic patient population was older (57.2 versus 43.2; P < 0.001) and had higher average body mass index (33.6 versus 29.5; P < 0.001). Eighty-three patients with DM and 270 nondiabetics were treated surgically (62% versus 78%; P < 0.001). Diabetic patients who were younger (54.6 versus 61.4; P = 0.01) with fewer comorbidities (1.7 versus 2.2; P = 0.04) were more frequently managed surgically. On univariate analysis, patients with DM more commonly developed any early infection (28.4% versus 21%; P = 0.049) but were no more likely to develop surgical site infection, or other postoperative complications. Older patient age, length of stay, baseline pulmonary disease, and concurrent abdominal injury were independent predictors of postoperative infection other than surgical site infection. Diabetics that developed infection had more comorbidities (2.4 versus 1.5; P < 0.001) and higher Injury Severity Score (24.1 versus 15.8; P = 0.003), and were more frequently insulin-dependent (72.7% versus 41%; P = 0.01). DISCUSSION: Independent of management strategy, diabetic patients were more likely to develop an infection after acetabular fracture. Insulin dependence was associated with postoperative infection on univariate analysis. Optimal selection of surgical candidates among patients with DM may limit postoperative infections.

Upper Extremity Wood Saw Injuries: Experience at a Single Level 1 Trauma Center.

BACKGROUND: Saw injuries are common, with more 75 000 occurring each year in the United States alone. While these injuries occur frequently, management strategies are not universally agreed upon, and data regarding outcomes and complications are lacking. We propose to provide a comprehensive picture of upper extremity saw injury patterns, management strategies, complications, and outcomes. METHODS: Patients presenting to a single level 1 trauma center between 2012 and2019 with upper extremity laceration, crush, or amputation were identified. In all, 10 721 patients were reviewed, and those without wood saw injuries were excluded. Patient demographic information, injury details, management strategy, and outcomes were collected. RESULTS: In all, 283 upper extremity wood saw injuries were analyzed. Injuries most commonly affected the fingers (92.2%), and the frequencies of simple lacerations and complicated injuries were nearly identical. The table saw was the most commonly implicated saw (48%) with more than half of the injuries being complicated, the most common being bone injury. Most patients were treated nonsurgically (81.3%), with the majority undergoing wound care in the emergency department followed by home antibiotics (68.2%). Subsequent complications were exceedingly rare (4.2%), with wound infection occurring in 5 patients. Amputations occurred in 19.4% of patients, leading to permanent functional impairment. CONCLUSIONS: Wood saw injuries are common, generating functional and financial burden. While injuries range in severity, management can typically be conducted within the emergency department with local wound care and outpatient oral antibiotics. Injury complications and long-term issues are rare. Ongoing efforts to promote saw safety are required to minimize the burden of these injuries.

Evaluating patient recall following operative orthopaedic trauma.

INTRODUCTION: Orthopedic trauma patients may have poor recall of their injuries and treatment. This may lead to poor adherence to instructions. The purposes of this project were to quantify recall about injury and treatment information, and to assess adherence to postoperative instructions and satisfaction with care. METHODS: A prospective cohort of 110 consecutive adult orthopaedic trauma patients treated for acute injury at a Level 1 trauma center were included. All had undergone surgical treatment of fractures of the pelvis or lower extremity. A brief survey to assess patient recall about injury and treatment knowledge, adherence to weightbearing and DVT recommendations and to evaluate patient satisfaction was administered during the first post-hospital clinic visit. RESULTS: Patients correctly answered 64% of recall-oriented questions. 82% and 83% of patients, respectively, reported adherence to their weightbearing restrictions and their DVT prophylaxis regimen, while 66% of patients reported adherence to both. Forty-two percent of non-adherent patients could not remember their weightbearing restrictions, while 78% of non-adherent patients could not remember their DVT prophylaxis regimen. Average patient satisfaction was 4.3 (range 1-5), with 15% of patients indicating neutral sentiment or dissatisfaction with their care. CONCLUSION: Orthopaedic trauma patients have poor recall, which likely reduces postoperative adherence and may impair patient satisfaction. A postoperative educational protocol focused on improving patient recall may be useful. LEVEL OF EVIDENCE: Level 4, prognostic.

Prolonged Time to Brake Following Lower Extremity Injuries.

INTRODUCTION: No guidelines exist for recommending return to driving. This study will examine time to brake (TTB) after lower extremity injuries versus in uninjured people. The potential effect of various types of lower extremity injuries on TTB will be measured. METHODS: Patients with injuries to the pelvis, hip, femur, knee, tibia, ankle, and foot underwent testing using a driving simulator to assess TTB. Comparison was with a control group of uninjured people. RESULTS: Two-hundred thirty-two patients with lower extremity injuries participated. The majority were in the tibia and ankle regions (47%). Mean TTB for control subjects was 0.74 seconds, compared with 0.83 for injured patients, noting a 0.09-second difference (P = 0.017). Left-sided injuries averaged TTB of 0.80 seconds, right-sided injuries averaged TTB of 0.86 seconds, and bilateral injuries averaged TTB of 0.83 seconds, all prolonged versus control subjects. The longest TTB was exhibited after ankle and foot injuries (0.89 seconds) while the shortest was after tibial shaft fractures (0.76 seconds). DISCUSSION: Any lower extremity injury caused a prolonged TTB compared with control patients. Left, right, and bilateral injuries all had longer TTB. Ankle and foot injuries experienced the longest TTB. Additional investigation is warranted to develop safe guidelines for return to driving.