Citations

Background: Treatment of severe patellar bone loss during revision total knee arthroplasty (TKA) is difficult. Patellar bone-grafting is a simple procedure that can improve patient outcomes following revision TKA. Description: The patient is prepared and draped in the usual sterile fashion. The previous longitudinal knee incision is utilized for exposure. Scar tissue is excised from the medial gutter. However, tissue in the lateral gutter is largely maintained. An assessment of the surrounding quadriceps and patellar scar tissue ensues. This tissue can be utilized to create an envelope for holding the bone graft in place. If insufficient tissue is present, fascia from the iliotibial band or vastus medialis, allograft fascia, or synthetics can be used. A careful assessment of component fixation and rotation is critical to the success of patellar bone-grafting. Component revision for aseptic loosening or malrotation should be performed in the usual fashion. During component revision, it is recommended to preserve any additional bone as autograft for the patellar bone-grafting procedure. Common sites of autograft harvest include the femoral box cut and proximal tibial resection. The patella is then addressed by carefully removing the previous implant to avoid additional bone loss. This step is performed with a combination of an oscillating saw, osteotomes, and high-speed burr. The retropatellar bone is then prepared by debriding excess soft tissue, cysts, or cement. A high-speed burr is then utilized to produce a punctate bleeding surface for bone-graft incorporation. The harvested tissue is closed around the perimeter of the patella with use of interrupted nonabsorbable sutures, leaving a window to pack in the bone graft. The bone graft (allograft and autograft) is morselized and place through the window. The optimal patellar thickness is variable. After packing the bone graft through the soft-tissue window, the thickness is measured with a caliper. It is recommended to acquire a thickness of >20 mm because bone-graft resorption and remodeling occur with knee range of motion. The remaining soft-tissue window is closed with use of nonabsorbable sutures. The knee is cycled through a range of motion to ensure optimal patellofemoral tracking. If necessary, a lateral release or medial soft-tissue advancement can be performed to ensure patellofemoral tracking is adequate. Finally, the wound is irrigated and closed in layers. Alternatives: Nonsurgical: Surgical: Gull-wing osteotomy Patellar resurfacing with biconvex patella Bulk allograft reconstruction Partial or complete patellectomy Patelloplasty Interpositional arthroplasty Tantalum metal-backed reconstruction Rationale: There is a myriad of surgical options for severe patellar bone loss following TKA. Patellar bone-grafting is simple, reproducible, and relatively cost-effective 1,2 , and avoids the need for the amount of bone for reconstruction that may be required for metal-backed or biconvex patellar implants 3,4 . The procedure allows for the restoration of the quadriceps lever arm, which may not be restored with other techniques, such as gull-wing osteotomy or patellectomy 5 . Patellar bone-grafting avoids the cost and risks of disease transmission associated with allograft reconstruction 6 . Finally, the procedure provides excellent long-term survivorship and patient-reported outcomes. Expected Outcomes: Following this procedure, patients should experience a reduction in knee pain and improved patient-reported outcomes 2,6 , with a prior study showing that the percentage of patients reporting anterior knee pain decreased from 51% to 27% following patellar bone-grafting. Patients also demonstrated an improvement in knee range of motion, with a mean increase in knee flexion of 7 o and knee extension of 2 o1 . Complications related to this procedure are minimal. Bone stock restoration can be utilized for patellar resurfacing in the future 1 . Radiographically, patellar bone resorption, loss of patellar height, and patellar remodeling do occur; however, despite these radiographic changes, Knee Society scores increased from 50 to 85 at the time of the latest follow-up. Important Tips:

Background: The cementation of a new liner into a well-fixed acetabular component is common during revision total hip arthroplasty (THA) for many indications, but most commonly for lack of a modern, compatible, highly cross-linked polyethylene (HXLPE) liner. However, little is known about the intermediate-term to long-term durability of this strategy. The purpose of this study was to evaluate the implant survivorship, risk of complications, clinical outcomes, and radiographic results of cementing a new HXLPE liner into a well-fixed acetabular component. Methods: We retrospectively identified 323 revision THAs in which a nonconstrained HXLPE liner was cemented into a well-fixed acetabular component. The mean age at the time of the revision THA was 63 years, and 50% of patients were female. The most common indications for revision THA were polyethylene wear and osteolysis (48%), aseptic femoral loosening (35%), and hip instability (8%). The mean follow-up was 9 years. Results: Polyethylene liner failure occurred in 11 cases (3%). In all cases, the cemented liner dissociated from the acetabular component. At 10 years, the survivorship free from any revision was 80% (95% confidence interval [CI], 75% to 84%) and the survivorship free from any reoperation was 77% (95% CI, 72% to 82%). The most common reason for re-revision was dislocation (45% of reoperations). A dislocation occurred in 17% of cases. Hips that underwent revision for instability were significantly more likely to dislocate compared with hips that underwent revision for liner wear (hazard ratio [HR], 2.3 [95% CI, 1.2 to 4.5]; p = 0.02). Elevated rim or face-changing liners were significantly more likely to dissociate than flat liners (HR, 9.0 [95% CI, 1.2 to 70.6]; p = 0.04). Conclusions: Cementation of a nonconstrained HXLPE liner into a well-fixed acetabular component during revision THA provided durable fixation with only a small number of failures at the cement interface (3%). Instability after this procedure remains a concern, but this is multifactorial in nature. These data support the continued use of this technique, when necessary, during revision THA. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Objectives/Introduction: Laryngology is an expanding field that has been increasingly incorporated into otolaryngology resident training programs nationwide. The exposure to the field is variable across training programs, despite the fact that laryngological complaints comprise a large proportion of consultations to otolaryngologists. Laryngology education is vital for the care of patients with voice, swallowing, and airway complaints as well as for the appropriate referral of patients to the laryngology team for specialized care. Speech-language pathologists (SLPs) specialized in voice and swallowing disorders are well-trained in the assessment and treatment for these populations. This team recently published a paper regarding the experience of laryngology education in residency. During analysis of the results, an interesting beneficial trend developed regarding the positive impact of exposure to SLPs. This appeared to be distinct and deserved further analysis and discussion. We propose that involving SLPs in resident education may greatly enhance their training in laryngology. Methods: As per our previous paper, a cross sectional, multi-institutional study was designed to assess the exposure of residents to laryngology. Descriptive statistics were obtained for questions involving exposure to SLPs. Fisher’s exact test was used to compare differences between groups. Results: Most respondents (135/151, 89.4%) indicated having SLPs specializing in voice and swallowing disorders in their departments, although only half (77/151, 51.0%) stated that they spent formal time with them during training. Results show that residents with formal training with SLPs were more comfortable interpreting videofluoroscopic swallow studies (VFSS) ( P = .0032). Residents with SLPs in their departments were also more likely to feel confident in terminology to describe different dysphonic voices ( P = .0213). Conclusion: Formal time with SLPs within otolaryngology residency programs varies across the country. Speech-language pathologists are a useful resource for laryngology resident training and should be included in their education.

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.

Background: Total knee arthroplasties (TKAs) with cementless fixation have been studied in multiple series with varying success. The aim of this study was to prepare a systematic review of the literature to evaluate clinical outcomes and revtpdelision rates of patients undergoing contemporary cementless TKA. Methods: A search of PubMed and MEDLINE was conducted for English-language articles published between 2005 and 2018 to identify studies examining survivorship and clinical outcomes of cementless TKAs. Studies that reported clinical and/or radiographic outcomes were included. Data collected included the number of TKAs, implant utilized, primary diagnosis, mean age and follow-up, implant survivorship, complications, revisions, and clinical outcome scores. All hybrid constructs and revision TKAs were excluded. Poisson regression analysis was used to determine the revision incidence rates per 1,000 person-years. Results: Forty-three studies with 10,447 TKAs met inclusion criteria, of which 8,187 were primary cementless TKAs. The mean follow-up was 7 years. The revision incidence per 1,000 person-years was 4.8 for all cementless designs. The complication rate for all cementless TKAs was 6%, with deep venous thrombosis being the most common complication. The mean postoperative Knee Society Score and Functional Score were 92 and 83, respectively. Conclusions: While newer-generation cementless designs have shown improved survivorship and clinical outcomes compared with earlier-generation cementless designs, the literature for cementless designs remains limited when compared with cemented designs. Further studies are needed to determine if cementless TKA can achieve the same benefits that have been realized with cementless total hip arthroplasty. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Abstract Background: Sex differences in non-small cell lung cancer (NSCLC) outcomes have been described. Immune-related adverse events (IRAEs) have emerged as a serious clinical problem in the use of immune checkpoint inhibitors (ICI). Risk factors for IRAEs and their association with response to therapy remain controversial. Sex differences in innate and adaptive immune responses have been observed but the association of these differences with IRAEs remains unclear. Therefore, we studied sex differences in IRAEs and their association with response to therapy. Methods: All patients with metastatic NSCLC treated with anti-PD1 and anti-PDL1 therapy at Mayo Clinic Rochester and Florida from 2015 to 2018 were reviewed. Patients receiving treatment at an outside facility with history autoimmune disorders or radiation-induced pneumonitis were excluded. Chi-square test was used to estimate differences in categorical data. Kaplan-Meier method was used for time-to-event analysis. Results: A total of 231 patients were identified; 120 (52%) were women and 111 (48%) were men. Baseline characteristics and ICI distribution were similar among groups. Women were more likely to experience IRAEs compared to men (48% vs. 31%, p<0.008). Among patients with IRAEs, women were more likely to be prescribed systemic steroids (63% vs. 41%, p<0.02). On the other hand, no significant differences were observed in the administration of intravenous steroids. Women were more likely to develop pneumonitis (23% vs. 12%, p<0.03) and arthralgias (17% vs. 3%, p<0.04). However, dermatologic toxicities (35% vs. 9%, p<0.002) were more commonly seen in men. In 17% of women the ICI was discontinued due to toxicity (men 7%). Besides sex, no other clinical characteristic was associated with increased IRAEs. Women with IRAEs were more likely to have a radiographic response compared with women without IRAEs (78% vs. 23%, p<0.0001), although this was not observed in men (37% vs. 26%, p>0.22). Better PFS was observed in women with IRAEs (10 months vs. 3.3 months, p<0.0006) compared to women without IRAEs. Conclusions: Women with metastatic NSCLC are more likely to experience IRAEs compared to men. We also observed sex differences in the frequency of certain IRAEs. In addition, an association between IRAEs and response to therapy was observed in women. Larger studies are needed to investigate the mechanisms underlying these associations. Citation Format: Narjust Duma, Abdel-Ghani Azzouqa, Siddhartha Yadav, Kahterine Hoversten, Clay Reed, Andrea Sitek, Elizabeth Enninga, Jonas Paludo, Lisa Kottschade, Aaron Mansfield, Rami Manochakian, Roxana Dronca, Alex Adjei. Sex differences in tolerability and response to immune checkpoint inhibitors in non-small cell lung cancer patients [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr A120.

Abstract Large-scale sequencing studies of hematologic malignancies have revealed notable epistasis among high-frequency mutations. One of the most striking examples of epistasis occurs for mutations in RNA splicing factors. These lesions are among the most common alterations in myeloid neoplasms and generally occur in a mutually exclusive manner, a finding attributed to their synthetic lethal interactions and/or convergent effects. Curiously, however, patients with multiple-concomitant splicing factor mutations have been observed, challenging our understanding of one of the most common examples of epistasis in hematologic malignancies. In this study, we performed bulk and single-cell analyses of patients with myeloid malignancy who were harboring ≥2 splicing factor mutations, to understand the frequency and basis for the coexistence of these mutations. Although mutations in splicing factors were strongly mutually exclusive across 4231 patients (q < .001), 0.85% harbored 2 concomitant bona fide splicing factor mutations, ∼50% of which were present in the same individual cells. However, the distribution of mutations in patients with double mutations deviated from that in those with single mutations, with selection against the most common alleles, SF3B1K700E and SRSF2P95H/L/R, and selection for less common alleles, such as SF3B1 non-K700E mutations, rare amino acid substitutions at SRSF2P95, and combined U2AF1S34/Q157 mutations. SF3B1 and SRSF2 alleles enriched in those with double-mutations had reduced effects on RNA splicing and/or binding compared with the most common alleles. Moreover, dual U2AF1 mutations occurred in cis with preservation of the wild-type allele. These data highlight allele-specific differences as critical in regulating the molecular effects of splicing factor mutations as well as their cooccurrences/exclusivities with one another.

Abstract Background Owing to patient intolerance or drug interactions, alternative agents to rifampin are needed for management of staphylococcal periprosthetic joint infection. In the current study, we evaluated rifabutin, rifapentine and rifampin, with and without vancomycin, in a rat model of foreign body osteomyelitis. Methods Proximal tibiae were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and a Kirschner wire (K-wire) implanted in each. After 4 weeks of infection, rifampin, rifabutin, or rifapentine were administered, alone or with vancomycin. Tibiae and K-wires were cultured, and medians were reported as log10 colony-forming units (CFUs) per gram of bone or log10 CFUs per K-wire, respectively. Results Rifampin, rifabutin or rifapentine administered with vancomycin yielded less MRSA from bones (0.10, 3.02, and 0.10 log10 CFUs/g, respectively) than did no treatment (4.36 log10 CFUs/g) or vancomycin alone (4.64 log10 CFUs/g) (both P ≤ .02). The K-wires of animals receiving no treatment or vancomycin monotherapy recovered medians of 1.76 and 2.91 log10 CFUs/g per K-wire, respectively. In contrast, rifampin, rifabutin and rifapentine administered with vancomycin yielded medians of 0.1 log10 CFUs per K-wire, respectively. Rifampin resistance was detected in a single animal in the rifampin monotherapy group. Conclusions Rifabutin or rifapentine with vancomycin were as active as rifampin with vancomycin against MRSA in rat foreign body osteomyelitis, suggesting that rifabutin and/or rifapentine may be alternatives to rifampin in the clinical management of staphylococcal periprosthetic joint infections.

Aims Arthrofibrosis is a relatively common complication after joint injuries and surgery, particularly in the knee. The present study used a previously described and validated rabbit model to assess the biomechanical, histopathological, and molecular effects of the mast cell stabilizer ketotifen on surgically induced knee joint contractures in female rabbits. Methods A group of 12 skeletally mature rabbits were randomly divided into two groups. One group received subcutaneous (SQ) saline, and a second group received SQ ketotifen injections. Biomechanical data were collected at eight, ten, 16, and 24 weeks. At the time of necropsy, posterior capsule tissue was collected for histopathological and gene expression analyses (messenger RNA (mRNA) and protein). Results At the 24-week timepoint, there was a statistically significant increase in passive extension among rabbits treated with ketotifen compared to those treated with saline (p = 0.03). However, no difference in capsular stiffness was detected. Histopathological data failed to demonstrate a decrease in the density of fibrous tissue or a decrease in α-smooth muscle actin (α-SMA) staining with ketotifen treatment. In contrast, tryptase and α-SMA protein expression in the ketotifen group were decreased when compared to saline controls (p = 0.007 and p = 0.01, respectively). Furthermore, there was a significant decrease in α-SMA (ACTA2) gene expression in the ketotifen group compared to the control group (p < 0.001). Conclusion Collectively, these data suggest that ketotifen mitigates the severity of contracture formation in a rabbit model of arthrofibrosis. Cite this article: Bone Joint Res 2020;9(6):302–310.

AbstractThere is interest in novel synovial fluid biomarkers for the detection of periprosthetic joint infection (PJI). Here, we assessed the diagnostic accuracy of 23 simple or sophisticated synovial fluid biomarkers for periprosthetic hip or knee infection detection. One hundred seven subjects were studied, 57 of whom had aseptic failure (AF) and 50 PJI. The following synovial fluid biomarkers were tested using spectrophotometric assays, immunoassays, lateral flow tests, or test strips: leukocyte count, monocyte percentage, lymphocyte percentage, neutrophil percentage, C‐reactive protein (CRP), glucose, lactate, granulocyte‐macrophage colony‐stimulating factor, interferon‐γ, interleukin‐1β (IL‐1β), IL‐2, IL‐4, IL‐5, IL‐6, IL‐8, IL‐10, IL‐12p70, IL‐13, IL‐17A, IL‐23, tumor necrosis factor‐α, α‐defensin, and leukocyte esterase. The best‐performing synovial fluid biomarkers to differentiate PJI from AF—that is, those with highest area under the curve compared to all other biomarkers—were leukocyte count, percent neutrophils and percent monocytes, CRP, and α‐defensin (P < .0001).