Females Are More Likely Than Males to Fill an Opioid Prescription in the Year After Anterior Cruciate Ligament Reconstruction.

Purpose: To report rates of preoperative and postoperative opioid use between male and female patients and to identify risk factors for extended opioid use following anterior cruciate ligament reconstruction (ACLR). Methods: Patients undergoing ACLR between 2011 and 2018 were identified from the PearlDiver database. The opioid refill rates for males vs females were compared at monthly intervals for 1 year after ACLR. Patients who filled an opioid prescription <3 months before surgery were classified as opioid users, while those who had never filled one were classified as nonopioid users. Results: Of 106,995 ACLR patients, 37,890 (35.4%) were opioid users <3 months before surgery, and 37,554 (35.1%) had never filled an opioid prescription. Of the preoperative opioid users, 20,413 (53.9%) were female and 17,477 (46.1%) were male (P < .001). Postoperatively, females were at higher risk of filling an opioid prescription at each monthly interval, except for the first month after surgery. The refill rate for opioid users was also higher than that for nonopioid users at each monthly interval after ACLR. In addition to patient sex, a preoperative diagnosis of anxiety/depression, low back pain, myalgia, a history of drug dependence, alcohol abuse, and tobacco use increased a patient's risk of filling an opioid prescription postoperatively. Conclusions: This study demonstrated that females are significantly more likely to be opioid users than males prior to ACLR and are more likely to continue to refill an opioid prescription in the year following surgery. Multiple risk factors were associated with prolonged postoperative opioid utilization, including female sex, anxiety/depression, low back pain, myalgia, a history of drug dependence, alcohol abuse, and tobacco use. Level of Evidence: Level III, retrospective cohort study.

Adoption of Robotic-Arm-Assisted Total Knee Arthroplasty Is Associated with Decreased Use of Articular Constraint and Manipulation under Anesthesia Compared to a Manual Approach.

Haptic robotic-arm-assisted total knee arthroplasty (RATKA) seeks to leverage three-dimensional planning, intraoperative assessment of ligament laxity, and guided bone preparation to establish and achieve patient-specific targets for implant position. We sought to compare (1) operative details, (2) knee alignment, (3) recovery of knee function, and (4) complications during adoption of this technique to our experience with manual TKA. We compared 120 RATKAs performed between December 2016 and July 2018 to 120 consecutive manual TKAs performed between May 2015 and January 2017. Operative details, lengths of stay (LOS), and discharge dispositions were collected. Tibiofemoral angles, Knee Society Scores (KSS), and ranges of motion were assessed until 3 months postoperatively. Manipulations under anesthesia, complications, and reoperations were tabulated. Mean operative times were 22 minutes longer in RATKA (p < 0.001) for this early cohort, but decreased by 27 minutes (p < 0.001) from the first 25 RATKA cases to the last 25 RATKA cases. Less articular constraint was used to achieve stability in RATKA (93 vs. 55% cruciate-retaining, p < 0.001; 3 vs. 35% posterior stabilized (PS), p < 0.001; and 4 vs. 10% varus-valgus constrained, p_ = _0.127). RATKA had lower LOS (2.7 vs. 3.4 days, p < 0.001). Discharge dispositions, tibiofemoral angles, KSS, and knee flexion angles did not differ, but manipulations were less common in RATKAs (4 vs. 17%, p = 0.013). We observed less use of constraint, shorter LOS, and fewer manipulations under anesthesia in RATKA, with no increase in complications. Operative times were longer, particularly early in the learning curve, but improved with experience. All measured patient-centered outcomes were equivalent or favored the newer technique, suggesting that RATKA with patient-specific alignment targets does not compromise initial quality. Observed differences may relate to improved ligament balance or diminished need for ligament release.

Thrombin spatial distribution determines protein C activation during hemostasis and thrombosis.

Rebalancing the hemostatic system by targeting endogenous anticoagulant pathways, like the protein C (PC) system, is being tested as a means of improving hemostasis in patients with hemophilia. Recent intravital studies of hemostasis demonstrated that, in some vascular contexts, thrombin activity is sequestered in the extravascular compartment. These findings raise important questions about the context-dependent contribution of activated PC (APC) to the hemostatic response, because PC activation occurs on the surface of endothelial cells. We used a combination of pharmacologic, genetic, imaging, and computational approaches to examine the relationships among thrombin spatial distribution, PC activation, and APC anticoagulant function. We found that inhibition of APC activity, in mice either harboring the factor V Leiden mutation or infused with an APC-blocking antibody, significantly enhanced fibrin formation and platelet activation in a microvascular injury model, consistent with the role of APC as an anticoagulant. In contrast, inhibition of APC activity had no effect on hemostasis after penetrating injury of the mouse jugular vein. Computational studies showed that differences in blood velocity, injury size, and vessel geometry determine the localization of thrombin generation and, consequently, the extent of PC activation. Computational predictions were tested in vivo and showed that when thrombin generation occurred intravascularly, without penetration of the vessel wall, inhibition of APC significantly increased fibrin formation in the jugular vein. Together, these studies show the importance of thrombin spatial distribution in determining PC activation during hemostasis and thrombosis.

Benefits of CT Scanning for the Management of Hip Arthritis and Arthroplasty.

INTRODUCTION: Imaging studies for preoperative planning of total hip arthroplasty (THA) are typically obtained by two-dimensional (2D) anteroposterior radiographs. However, CT imaging has proven to be a valuable tool that may be more accurate than standard radiographs. The purpose of this review was to report on the current literature to assess the utility of CT imaging for preoperative planning of THA. Specifically, we assessed its utility in the evaluation of: 1) hip arthritis; 2) femoral head osteonecrosis; 3) implant size prediction; 4) component alignment; 5) limb length evaluation; and 6) radiation exposure. MATERIALS AND METHODS: A literature search was performed using search terms "computed tomography", "radiograph", "joint" "alignment", "hip," and "arthroplasty". Our initial search returned a total of 562 results. After applying our criteria, 26 studies were included. RESULTS: CT scans were found to be more accurate than radiographs in predicting implant size and alignment preoperatively and provide improved visualization of extraarticular deformities that may be essential to consider when planning a THA. Although radiation is a potential concern, newer imaging protocols have minimized the radiation to levels comparable to x-ray. CONCLUSION: The current literature suggests that CT has several advantages over radiographs for preoperative planning of THA including more accurate planning of implant size, component alignment, and postoperative leg length. It is also superior to x-ray in identifying extraarticular hip deformities using the minimum effective dose for CT and the minimum scan length required by templating software. The radiation can be reduced to values similar to radiography.

Interrelationships between structure and function during the hemostatic response to injury.

Extensive studies have detailed the molecular regulation of individual components of the hemostatic system, including platelets, coagulation factors, and regulatory proteins. Questions remain, however, about how these elements are integrated at the systems level within a rapidly changing physical environment. To answer some of these questions, we developed a puncture injury model in mouse jugular veins that combines high-resolution, multimodal imaging with functional readouts in vivo. The results reveal striking spatial regulation of platelet activation and fibrin formation that could not be inferred from studies performed ex vivo. As in the microcirculation, where previous studies have been performed, gradients of platelet activation are readily apparent, as is an asymmetrical distribution of fibrin deposition and thrombin activity. Both are oriented from the outer to the inner surface of the damaged vessel wall, with a greater extent of platelet activation and fibrin accumulation on the outside than the inside. Further, we show that the importance of P2Y12 signaling in establishing a competent hemostatic plug is related to the size of the injury, thus limiting its contribution to hemostasis to specific physiologic contexts. Taken together, these studies offer insights into the organization of hemostatic plugs, provide a detailed understanding of the adverse bleeding associated with a widely prescribed class of antiplatelet agents, and highlight differences between hemostasis and thrombosis that may suggest alternative therapeutic approaches.

Coordination of platelet agonist signaling during the hemostatic response in vivo.

The local microenvironment within an evolving hemostatic plug shapes the distribution of soluble platelet agonists, resulting in a gradient of platelet activation. We previously showed that thrombin activity at a site of vascular injury is spatially restricted, resulting in robust activation of a subpopulation of platelets in the hemostatic plug core. In contrast, adenosine 5'-diphosphate (ADP)/P2Y12 signaling contributes to the accumulation of partially activated, loosely packed platelets in a shell overlying the core. The contribution of the additional platelet agonists thromboxane A2 (TxA2) and epinephrine to this hierarchical organization was not previously shown. Using a combination of genetic and pharmacologic approaches coupled with real-time intravital imaging, we show that TxA2 signaling is critical and nonredundant with ADP/P2Y12 for platelet accumulation in the shell region but not required for full platelet activation in the hemostatic plug core, where thrombin activity is highest. In contrast, epinephrine signaling is dispensable even in the presence of a P2Y12 antagonist. Finally, dual P2Y12 and thrombin inhibition does not substantially inhibit hemostatic plug core formation any more than thrombin inhibition alone, providing further evidence that thrombin is the primary driver of platelet activation in this region. Taken together, these studies show for the first time how thrombin, P2Y12, and TxA2 signaling are coordinated during development of a hierarchical organization of hemostatic plugs in vivo and provide novel insights into the impact of dual antiplatelet therapy on hemostasis and thrombosis.