Citations

Background: The U.S. Food and Drug Administration has approved a bupivacaine and meloxicam extended-release (ER) intra-articular injection for pain during total knee arthroplasty (TKA). However, the real-world evidence with regard to analgesic efficacy of that medication has been limited. This randomized clinical trial investigated the efficacy of this new medication compared with our standard periarticular injection for postoperative analgesia after primary TKA. Methods: Eligible patients undergoing primary, unilateral TKA for osteoarthritis at our academic center were enrolled. Patients were blinded and were randomized 1:1 to the bupivacaine-meloxicam ER (ZYNRELEF) injection group or the standard injection (ropivacaine, ketorolac, epinephrine) control group. A standardized, multimodal analgesic pathway was implemented. Numeric Rating Scale (NRS) pain scores and tallies of opioid consumption were collected. The primary outcome was the area under the curve (AUC) for NRS pain, adjusted for opioid consumption, over 72 hours. The minimal clinically important difference was considered to be 30%. Power analysis determined a minimum of 44 patients per group. The final groups included 53 patients in the experimental group and 48 patients in the control group. Results: Similar postoperative analgesia was observed, with an AUC for the adjusted NRS pain score up to 72 hours of 331 in the experimental group and 373 in the control group (p = 0.09). The mean maximum NRS pain scores were similar and reflected good, but not complete, analgesia. Scores were 3 to 5 on the day of the surgery, 4 to 6 on postoperative day (POD) 1, 5 to 6 on POD 2, and 4 to 5 on POD 3 (p > 0.05). One patient in the experimental group and 2 patients in the control group had early postoperative complications, none of which was deemed to be related to the analgesic choice. Conclusions: This randomized clinical trial demonstrated similar analgesia with a bupivacaine-meloxicam ER solution and a standard periarticular injection up to 72 hours after primary TKA. Cost, reimbursement, and convenience may ultimately prove to be more important than analgesic differences when choosing between these 2 effective options for managing postoperative pain. Level of Evidence: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Aims Spinal anaesthesia has seen increased use in contemporary primary total knee arthroplasties (TKAs). However, controversy exists about the benefits of spinal in comparison to general anaesthesia in primary TKAs. This study aimed to investigate the pain control, length of stay (LOS), and complications associated with spinal versus general anaesthesia in primary TKAs from a single, high-volume academic centre. Methods We retrospectively identified 17,690 primary TKAs (13,297 patients) from 2001 to 2016 using our institutional total joint registry, where 52% had general anaesthesia and 48% had spinal anaesthesia. Baseline characteristics were similar between cohorts with a mean age of 68 years (SD 10), 58% female (n = 7,669), and mean BMI of 32 kg/m2 (SD 7). Pain was evaluated using oral morphine equivalents (OMEs) and numerical pain rating scale (NPRS) data. Complications including 30- and 90-day readmissions were studied. Data were analyzed using an inverse probability of treatment weighted model based on propensity score that included many patient and surgical factors. Mean follow-up was seven years (2 to 18). Results Patients treated with spinal anaesthesia required fewer postoperative OMEs (p < 0.001) and had lower NPRS scores (p < 0.001). Spinal anaesthesia also had fewer cases of altered mental status (AMS; odds ratio (OR) 1.3; p = 0.044), as well as 30-day (OR 1.4; p < 0.001) and 90-day readmissions (OR 1.5; p < 0.001). General anaesthesia was associated with increased risk of any revision (OR 1.2; p = 0.021) and any reoperation (1.3; p < 0.001). Conclusion In the largest single institutional report to date, we found that spinal anaesthesia was associated with significantly lower OME use, lower risk of AMS, and lower overall 30- and 90-day readmissions following primary TKAs. Additionally, spinal anaesthesia was associated with reduced risk of any revision and any reoperation after accounting for numerous patient and operative factors. When possible and safe, spinal anaesthesia should be considered in primary TKAs. Cite this article: Bone Joint J 2022;104-B(11):1209–1214.

Abstract Somatic mutations in UBA1 cause vacuoles, E1 ubiquitin-activating enzyme, X-linked, autoinflammatory somatic (VEXAS) syndrome, an adult-onset inflammatory disease with an overlap of hematologic manifestations. VEXAS syndrome is characterized by a high mortality rate and significant clinical heterogeneity. We sought to determine independent predictors of survival in VEXAS and to understand the mechanistic basis for these factors. We analyzed 83 patients with somatic pathogenic variants in UBA1 at p.Met41 (p.Met41Leu/Thr/Val), the start codon for translation of the cytoplasmic isoform of UBA1 (UBA1b). Patients with the p.Met41Val genotype were most likely to have an undifferentiated inflammatory syndrome. Multivariate analysis showed ear chondritis was associated with increased survival, whereas transfusion dependence and the p.Met41Val variant were independently associated with decreased survival. Using in vitro models and patient-derived cells, we demonstrate that p.Met41Val variant supports less UBA1b translation than either p.Met41Leu or p.Met41Thr, providing a molecular rationale for decreased survival. In addition, we show that these 3 canonical VEXAS variants produce more UBA1b than any of the 6 other possible single-nucleotide variants within this codon. Finally, we report a patient, clinically diagnosed with VEXAS syndrome, with 2 novel mutations in UBA1 occurring in cis on the same allele. One mutation (c.121 A&gt;T; p.Met41Leu) caused severely reduced translation of UBA1b in a reporter assay, but coexpression with the second mutation (c.119 G&gt;C; p.Gly40Ala) rescued UBA1b levels to those of canonical mutations. We conclude that regulation of residual UBA1b translation is fundamental to the pathogenesis of VEXAS syndrome and contributes to disease prognosis.

Background: For elective total joint arthroplasty, tranexamic acid (TXA) is considered safe and efficacious. However, evidence of TXA’s safety in high-risk patients undergoing nonelective surgery for hip fracture is sparse. This study aimed to assess whether TXA administration to high-risk patients with an intertrochanteric (IT) hip fracture increased the risk of thromboembolic complications or mortality. Methods: All patients treated surgically for IT hip fracture between 2015 and 2019 across 4 hospitals of a single hospital system were considered. High- versus low-risk patients and those receiving TXA versus no TXA treatment were identified. Propensity scores adjusted for risk differences between patient groups with TXA and no TXA administration were calculated for (1) high-risk patients (n = 141) and (2) the entire population (n = 316). Postoperative mortality, deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction (MI), and stroke within 90 days of surgery were evaluated. Results: No association between TXA administration and increased risk of mortality or complications in either group was identified. Specifically, out of 282 matched high-risk patients, no differences in mortality (odds ratio [OR], 0.97 [95% confidence interval (CI), 0.90, 1.05]), DVT (OR, 0.97 [95% CI, 0.93, 1.00]), PE (OR 1.00 [95% CI, 0.95, 1.05]), MI (OR, 1.04 [95% CI, 0.98, 1.10]), or stroke (OR, 1.00 [95% CI, 0.95, 1.05]) were identified. Conclusions: In our review of propensity-matched high-risk patients undergoing surgical repair for IT fracture, we found that TXA administration compared with no TXA administration was not associated with an increased risk of mortality, DVT, PE, MI, or stroke within 90 days of surgery. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Background: The specific advantages of spinal anesthesia compared with general anesthesia for primary total hip arthroplasty (THA) remains unknown. Therefore, this study aimed to investigate the pain control, length of stay, and postoperative outcomes associated with spinal anesthesia compared with general anesthesia in a large cohort of primary THAs from a single, high-volume academic institution. Methods: We retrospectively identified 13,730 primary THAs (11,319 patients) from 2001 to 2016 using our total joint registry. Of these cases, 58% had general anesthesia and 42% had spinal anesthesia. The demographic characteristics were similar between groups, with mean age of 64 years, 51% female, and mean body mass index (BMI) of 31 kg/m 2 . Data were analyzed using an inverse probability of treatment weighted model based on a propensity score that accounted for numerous patient and operative factors. The mean follow-up was 6 years. Results: Patients treated with spinal anesthesia had lower Numeric Pain Rating Scale (NPRS) scores (p < 0.001) and required fewer postoperative oral morphine equivalents (OMEs) at all time points evaluated (p < 0.001). Patients treated with spinal anesthesia also had shorter hospital length of stay (p = 0.02), fewer altered mental status events (odds ratio [OR], 0.7; p = 0.02), and fewer intensive care unit (ICU) admissions (OR, 0.7; p = 0.01). There was no difference in the incidence of deep vein thrombosis (p = 0.8), pulmonary embolism (p = 0.4), 30-day readmissions (p = 0.17), 90-day readmissions (p = 0.18), all-cause revisions (p = 0.17), or all-cause reoperations (p = 0.14). Conclusions: In this large, single-institution study, we found that spinal anesthesia was associated with reduced pain scores and OME use postoperatively. Furthermore, spinal anesthesia resulted in fewer altered mental status events and ICU admissions. These data favor the use of spinal anesthesia in primary THAs. Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Background: Tranexamic acid (TXA) is considered safe and efficacious for elective total joint arthroplasty. However, evidence of TXA’s safety in high-risk patients with hip fracture requiring nonelective arthroplasty has been lacking. This study aimed to assess whether TXA administration to high-risk patients with a hip fracture requiring arthroplasty increased the risk of thrombotic complications or mortality. Methods: All patients who underwent hip hemiarthroplasty (HHA) or total hip arthroplasty (THA) for displaced femoral neck fractures between 2011 and 2019 at 4 sites within 1 hospital system were retrospectively identified. Patients were grouped by risk (high-risk or low-risk) and TXA treatment (with or without TXA). Propensity scores were used for risk adjustment in comparisons between surgery with and without TXA for only the high-risk group (n = 1,066) and the entire population (n = 2,166). Differences in the occurrence of postoperative mortality, deep venous thrombosis, pulmonary embolism, myocardial infarction, and stroke within 90 days of hip arthroplasty were evaluated. Results: TXA administration was not associated with an increased risk of thrombotic complications or mortality within 90 days in either high-risk or all-patient groups. Specifically, among 1,066 matched high-risk patients who did not or did receive TXA, there were no significant differences in mortality (14.82% and 10.00%; p = 0.295), deep venous thrombosis (3.56% and 3.04%; p = 0.440), pulmonary embolism (2.44% and 1.96%; p = 0.374), myocardial infarction (3.38% and 2.14%; p = 0.704), or stroke (4.32% and 5.71%; p = 0.225). Conclusions: In our review of 1,066 propensity-matched high-risk patients undergoing hip arthroplasty for displaced femoral neck fractures, we found that TXA administration (compared with no TXA administration) was not associated with an increased risk of mortality, deep venous thrombosis, pulmonary embolism, myocardial infarction, or stroke. Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Background: Spinal anesthesia provides several benefits for patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA), but historically comes at the cost of slow and unpredictable return of lower-extremity motor function related to the use of long-acting local anesthetics. In this prospective, double-blinded, randomized clinical trial we sought to determine if an alternative local anesthetic, mepivacaine, would allow more consistent return of motor function compared with low-dose bupivacaine spinal anesthesia during primary THA and TKA. Methods: This trial was conducted at a single academic institution. Prior to trial initiation an internal pilot study determined that 154 patients were required to achieve 80% power. Patients were randomized in a 1:1 fashion with use of advanced computerized stratification based on procedure, age group, sex, and body mass index. Following the surgical procedure, motor function was assessed every 15 minutes in the nonoperative lower extremity according to the Bromage scale and discontinued once Bromage 0 was achieved (spontaneous movement at hip, knee, and ankle). Results: Return of lower-extremity function was more predictable in patients who received mepivacaine than in those who received low-dose bupivacaine. Among patients who received mepivacaine, 1% achieved motor function return beyond 5 hours compared with 11% of patients who received bupivacaine (p = 0.013). The mean time to return of lower-extremity motor function was 26 minutes quicker in patients who received mepivacaine (185 minutes; 95% confidence interval, 174 to 196 minutes) compared with low-dose bupivacaine (210 minutes; 95% confidence interval, 193 to 228 minutes) (p = 0.016). There were no significant differences in safety outcomes including pain scores, time to participation in physical therapy, incidence of orthostatic hypotension, urinary retention, or transient neurologic symptoms in patients receiving mepivacaine compared with low-dose bupivacaine. Conclusions: In patients undergoing primary THA and TKA, spinal anesthesia with mepivacaine allowed more consistent return of lower-extremity motor function compared with low-dose bupivacaine, without a concomitant increase in complications potentially associated with spinal anesthetics. This is particularly of value in an era of short-stay and outpatient surgical procedures. Level of Evidence: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

144 Background: Many patients require hospitalization after mastectomy, predominantly for pain management and treatment of postoperative nausea and vomiting (PONV). In order to improve a woman's perioperative experience after mastectomy and facilitate mastectomy on an outpatient basis, we initiated a clinical pathway for perioperative management of unilateral mastectomy patients at Mayo Clinic Rochester. Methods: The clinical pathway consists of preoperative oral medications (celecoxib and gabapentin), preoperative ultrasound guided paravertebral block using bupivacaine, intraoperative anesthesia management with total intravenous anesthetic, and minimal use of long-acting opioids and postoperative acetaminophen and oxycodone. All patients are evaluated by the surgical team on the afternoon after surgery and if patients are recovering well are discharged on the day of surgery. The following morning, the surgical team telephones the patient to follow up on management of pain, nausea or vomiting, and drain output. Results: Eighteen patients have been treated on this clinical pathway. Mean age of patients was 66 (range 51-81). Majority of patients (n=16, 89%) underwent unilateral mastectomy with sentinel lymph node biopsy, with 1 patient undergoing bilateral mastectomy and 1 patient undergoing mastectomy and axillary dissection. All patients are evaluated by the surgical team on the afternoon of surgery. Fourteen patients (78%) were without evidence of hematoma or PONV, pain was well-controlled on oral medications and they were discharged on the day of surgery. On morning after telephone calls, pain scale ratings ranged from 1 to 3 and no patients verbalized complaints of nausea. Four patients (22%) treated on this clinical pathway required overnight observation in the hospital, one for urinary retention, two for pain control, and one for high sanguineous drain output. Conclusions: The clinical pathway presented provides preemptive analgesia and regional anesthesia for patients undergoing mastectomy, enabling the majority of patients to be discharged on the day of surgery. The clinical pathway is a safe and effective way to improve the perioperative experience of breast surgery patients and decrease hospital admission.