Management of Scaphotrapeziotrapezoid Osteoarthritis: A Critical Analysis Review.

¼ The scaphotrapeziotrapezoid (STT) joint is a common location of degenerative osteoarthritis (OA) in the wrist.¼ STT OA may occur in isolation or with concomitant thumb carpometacarpal joint (CMCJ) OA or scapholunate advanced collapse (SLAC) and other wrist OA patterns.¼ Nonoperative management strategies include activity modification, bracing, anti-inflammatory medications, occupational therapy, and injections.¼ Surgical treatment may be determined by whether the STT OA occurs in isolation or with concomitant thumb CMCJ or SLAC OA and includes STT arthrodesis, distal scaphoid excision with or without interposition or implant arthroplasty, trapeziectomy with proximal trapezoid excision, four-corner fusion in combination with scaphoid/radial column excision, and proximal row carpectomy.

No Differences in Exercise Performance, Perceptual Response, or Safety Were Observed Among 3 Blood Flow Restriction Devices.

Purpose: To compare 3 separate blood flow restriction (BFR) systems in their capacity to reduce repetitions to failure, impact perceptual responses, and cause adverse events during a low-load free-flow exercise. Methods: The study included healthy subjects aged 18 years or older who presented to an ambulatory-care sports medicine clinic. On day 1, participants' demographic characteristics and anthropomorphic measurements were recorded. Each participant performed dumbbell biceps curl repetitions to failure using 20% of his or her 1-repetition maximum weight with each arm. Participants were exposed to 3 different tourniquet systems for familiarization. On day 2, each participant's arm was randomized to a cuff system, and the participant performed 2 sets of biceps curl repetitions to failure with the cuff inflated. Repetitions to failure, rating of perceived effort (RPE), rating of perceived discomfort, and pulse oxygenation levels were recorded after each set. On day 3, participants completed a survey of their perceived delayed-onset muscle soreness. Results: The final analysis was performed on 42 arms, with 14 limbs per system. The study population had a mean age of 28.7 ± 2.4 years and a mean body mass index of 24.9 ± 4.3. All 3 systems successfully reduced repetitions to failure compared with unrestricted low-load exercise from baseline to BFR set 1 and from baseline to BFR set 2. There were no significant between-group differences among BFR systems regarding the number of repetitions to failure performed at baseline versus BFR set 1 or BFR set 2. The Delfi Personalized Tourniquet System (PTS) cohort had the greatest reductions in repetitions to failure from BFR set 1 to BFR set 2 (P = .002) and reported the highest RPE after set 2 (P = .025). Conclusions: The Delfi PTS, SmartCuffs Pro, and BStrong BFR systems were each safe and were able to significantly reduce repetitions to failure compared with a low-load free-flow condition when used in a BFR exercise protocol. The Delfi PTS system may produce a higher RPE with prolonged use in comparison to the other systems. Level of Evidence: Level II, prospective cohort study.

Increasing severity of preoperative anemia is associated with higher postoperative medical and surgical complications after primary shoulder arthroplasty.

BACKGROUND: Anemia is a major cause of morbidity worldwide and compounds numerous medical conditions. Studies have found associations between anemia and both medical and surgical complications after shoulder arthroplasty (SA); however, most of these studies have used commercially available national databases with limited information on outcomes and typically short-term follow-up. Our study sought to evaluate the midterm outcomes of primary SA at a single institution when stratified by the degree of preoperative anemia. METHODS: Between 2000 and 2020, 5231 primary SA (477 hemiarthroplasties, 2091 anatomic total SA, and 2335 reverse SA) with preoperative hematocrit values available and a minimum follow-up of 2 years were collected from a single-institution joint registry database. The severity of anemia was subclassified as no anemia (hematocrit >39% for males, >36% for females; n = 4194 [80.2%]), mild anemia (hematocrit 33%-39% for males, 33%-36% for females; n = 742 [14.2%]), and moderate-to-severe anemia (hematocrit <33% for both males and females; n = 295 [5.6%]). The mean follow-up time for the entire cohort was 5.9 years (range, 2-22 years). Medical and surgical complications, reoperations, revisions, and implant survivorship were assessed. RESULTS: SA with moderate-to-severe anemia had the highest rate of nonfatal and nontransfusion medical complications (5.1%) relative to the nonanemic (1.2%; P < .001) and mild anemic groups (1.5%; P < .001). Similarly, SA with moderate-to-severe anemia had the highest rate of surgical complications (19.3%) compared with mild anemia (14.3%; P = .044) and no anemia (11.6%; P < .001). Postoperative transfusion was most frequent in the moderate-to-severe anemia cohort (40.3%) compared with the mild anemia (14.2%; P < .001) and nonanemic groups (2.5%; P < .001). Furthermore, SA who received postoperative transfusions had a higher risk of nonfatal medical complications (8.2% vs. 1.0%; P < .001), 90-day mortality (1.5% vs. 0.03%; P = .001), and surgical complications (19.5% vs. 12.0%; P < .001) when compared with those without transfusion. CONCLUSIONS: Moderate-to-severe anemia (hematocrit <33% for both males and females) was identified in approximately 5.6% of patients who underwent SA at a single institution and was associated with increased medical and surgical complications. Patients who received postoperative transfusions presented elevated rates of medical complications, 90-day mortality, and surgical complications. Health care teams should be aware of these risks in order to provide more individualized medical optimization and postoperative monitoring.

Parathyroid hormone therapy improves MRSA-infected fracture healing in a murine diabetic model.

Introduction: Diabetes mellitus (DM) impairs fracture healing and is associated with susceptibility to infection, which further inhibits fracture healing. While intermittent parathyroid hormone (1-34) (iPTH) effectively improves fracture healing, it is unknown whether infection-associated impaired fracture healing can be rescued with PTH (teriparatide). Methods: A chronic diet-induced type 2 diabetic mouse model was used to yield mice with decreased glucose tolerance and increased blood glucose levels compared to lean-fed controls. Methicillin-resistant Staphylococcus aureus (MRSA) was inoculated in a surgical tibia fracture model to simulate infected fracture, after which mice were treated with a combination of antibiotics and adjunctive teriparatide treatment. Fracture healing was assessed by Radiographic Union Scale in Tibial Fractures (RUST), micro-computed tomography (µCT), biomechanical testing, and histology. Results: RUST score was significantly poorer in diabetic mice compared to their lean nondiabetic counterparts. There were concomitant reductions in micro-computed tomography (µCT) parameters of callus architecture including bone volume/total volume, trabecular thickness, and total mineral density in type 2 diabetes mellitus (T2DM) mice. Biomechanicaltesting of fractured femora demonstrated diminished torsional rigidity, stiffness, and toughness to max torque. Adjuvant teriparatide treatment with systemic antibiotic therapy improved numerous parameters of bone microarchitecture bone volume, increased connectivity density, and increased trabecular number in both the lean and T2DM group. Despite the observation that poor fracture healing in T2DM mice was further impaired by MRSA infection, adjuvant iPTH treatment significantly improved fracture healing compared to antibiotic treatment alone in infected T2DM fractures. Discussion: Our results suggest that teriparatide may constitute a viable adjuvant therapeutic agent to improve bony union and bone microarchitecture to prevent the development of septic nonunion under diabetic conditions.

Subacromial Balloon Implantation for the Treatment of Irreparable Posterosuperior Rotator Cuff Tears.

Despite the development of various therapeutic options, surgical management of irreparable rotator cuff tears (IRCTs) remains controversial. Recently, implantation of a biodegradable subacromial balloon spacer (InSpace, Stryker Corporation; Kalamazoo, MI) has gained considerable interest for the treatment of certain IRCTs. The reported outcome of balloon implantation has not been consistent, likely due to differing indications and technical approaches. The purpose of this article is to present a reproducible arthroscopic technique for implantation of a subacromial balloon and to review the literature published to date, regarding the efficacy and outcomes of this procedure.

Percutaneous Ablation, Osteoplasty, Reinforcement, and Internal Fixation for Pain and Ambulatory Function in Periacetabular Osteolytic Malignancies.

Background Osteolytic neoplasms to periacetabular bone frequently cause pain and fractures. Immediate recovery is integral to lifesaving ambulatory oncologic care and maintaining quality of life. Yet, open acetabular reconstructive surgeries are associated with numerous complications that delay cancer treatments. Purpose To determine the effectiveness for short- and long-term pain and ambulatory function following percutaneous ablation, osteoplasty, reinforcement, and internal fixation (AORIF) for periacetabular osteolytic neoplasm. Materials and Methods This retrospective observational study evaluated clinical data from 50 patients (mean age, 65 years ± 14 [SD]; 25 men, 25 women) with osteolytic periacetabular metastases or myeloma. The primary outcome of combined pain and ambulatory function index score (range, 1 [bedbound] through 10 [normal ambulation]) was assessed before and after AORIF at 2 weeks and then every 3 months up to 40 months (overall median follow-up, 11 months [IQR, 4-14 months]). Secondary outcomes included Eastern Cooperative Oncology Group (ECOG) score, infection, transfusion, 30-day readmission, mortality, and conversion hip arthroplasty. Serial radiographs and CT images were obtained to assess the hip joint integrity. The paired t test or Wilcoxon signed-rank test and Kaplan-Meier analysis were used to analyze data. Results Mean combined pain and ambulatory function index scores improved from 4.5 ± 2.4 to 7.8 ± 2.1 (P < .001) and median ECOG scores from 3 (IQR, 2-4) to 1 (IQR, 1-2) (P < .001) at the first 2 weeks after AORIF. Of 22 nonambulatory patients, 19 became ambulatory on their first post-AORIF visit. Pain and functional improvement were retained beyond 1 year, up to 40 months after AORIF in surviving patients. No hardware failures, surgical site infections, readmissions, or delays in care were identified following AORIF. Of 12 patients with protrusio acetabuli, one patient required a conversion hemiarthroplasty at 24 months. Conclusion The ablation, osteoplasty, reinforcement, and internal fixation, or AORIF, technique was effective for short- and long-term improvement of pain and ambulatory function in patients with periacetabular osteolytic neoplasm. © RSNA, 2023.

Demographics and Characteristics of Orthopaedic Surgery Residency Program Directors: A Cross-sectional Review.

To date, there has been a paucity of research evaluating the demographics, characteristics, and surgical training of orthopaedic residency program directors (PDs). Purpose: To determine the objective characteristics of orthopaedic residency PDs by analyzing their demographic characteristics, academic backgrounds, institutional histories, research productivity, and professional leadership affiliations. Methods: Data for each PD were collected by searching publicly available curriculum vitae, LinkedIn, Healthgrades, Doximity, and/or institutional biographies and consolidated into a database. Research productivities were collected by searching PubMed and Scopus. Results: Of the 210 PDs, 188 (89.5%) were male and 22 (10.5%) were female. One hundred seventy-four (82.9%) were non-Hispanic White, 14 (6.7%) Asian American and Pacific Islander, 12 (5.7%) Black or African American, 4 (1.9%) Hispanic or Latino, and 6 (2.9%) other/unknown. Twenty-four (11.4%) PDs had a military affiliation. Moreover, the most common subspecialties among orthopaedic PDs were orthopaedic traumatology (19.5%, n = 41), sports medicine (15.7%, n = 33), and hand surgery (11.9%, n = 25). The mean Scopus h-index, total number of publications at the time of data collection (June 2022), and total number of citations for all orthopaedic residency PDs were 10.5 ± 9.5, 33.9 ± 51.0, and 801.9 ± 1,536.4, respectively. Among all PDs, the mean tenure in the position was 8.9 ± 6.2 years to date, and the mean time from completion of residency to appointment as PD was 10.0 ± 6.2 years. Conclusions: Among orthopaedic surgery residency PDs, there is sparse female and minority representation. Overarchingly, orthopaedic PDs are White men in their early 50s. Moreover, 59.1% of PDs were appointed at an institution where they completed medical school, residency, or fellowship. orthopaedic traumatology (19.5%), sports medicine (15.7%), and hand surgery (11.9%) were the subspecialties most represented in current orthopaedic surgery PDs. Clinical Relevance: This study outlines important demographic characteristics among orthopaedic surgery residency PDs. Level of Evidence: III.

Outcome of Multidisciplinary Treatment of Merkel Cell Carcinoma of the Hand and Wrist.

BACKGROUND/AIM: Skin cancers are the most common malignancy of the hand and wrist. Merkel cell carcinoma (MCC) is a rare, aggressive non-melanoma skin cancer arising from cutaneous neuroendocrine cells and is known for local and distant recurrence. The purpose of the current study was to examine the treatment outcome of patients with MCC of the hand and wrist. PATIENTS AND METHODS: We reviewed 25 patients (18 males:7 females) with MCC that occurred in the hand and wrist. The mean age at the time of biopsy of 71±11 years. RESULTS: Tumors were located on the hand (n=13), finger/thumb (n=9), and wrist (n=3). Local control included wide local excision (n=22). This included 21 non-amputation resections and one 5th digit ray amputation. Sentinel lymph node biopsy was performed in 21 patients with positive nodal disease in seven cases. Adjuvant radiotherapy was delivered to the primary site in 17 patients and additionally to the regional lymph node basin in six patients. Recurrence within five years was noted in 40% of patients (mean time to recurrence 18.4±20.6 months). Recurrence-free and disease-specific survival rates at 5-years were 54.8% and 67.6%. CONCLUSION: MCC is a rare cutaneous neuroendocrine carcinoma with a high propensity for regional nodal spread. Despite aggressive local treatment, adjuvant radiotherapy to the primary site and regional nodes, MCC of the hand and wrist has a high rate of recurrence and mortality within five years of diagnosis.

Chronic Q fever presenting as bilateral extensor tenosynovitis: a case report and review of the literature.

Musculoskeletal manifestations of Coxiella burnetii are rare. We describe an elderly, immunosuppressed male with bilateral Coxiella burnetii extensor tenosynovitis treated with incision and debridement and chronic doxycycline and hydroxychloroquine. Additionally, disease etiology, risk factors, pertinent features of the history, testing modalities, and treatment strategies of musculoskeletal Q fever are reviewed.

Impact of sickle cell disease in shoulder arthroplasty: a matched cohort analysis.

BACKGROUND: Sickle cell disease (SCD) is a genetic disorder of abnormal hemoglobin synthesis that is known to cause glenohumeral avascular necrosis (AVN). Little has been published on the use of shoulder arthroplasty (SA) for the treatment of glenohumeral AVN in SCD. We report on the clinical and radiographic results and postoperative complications following SA in the patient cohort. METHODS: A retrospective review was performed identifying 17 primary SAs (9 hemiarthroplasties, 7 anatomic total SAs, and 1 reverse total SA) in patients with a confirmed diagnosis of SCD and a minimum of 2-year follow-up. This cohort was matched (1:2) according to age, sex, body mass index, type of prosthesis, and year of surgery with patients who had undergone hemiarthroplasty or total SA for osteoarthritis (OA) or reverse total SA for cuff tear arthropathy. Outcomes included the visual analog scale (VAS) for pain, American Shoulder and Elbow Surgeons score, range of motion, and strength measurements in forward elevation (FE), external rotation (ER), and internal rotation (IR). RESULTS: Our cohort included 9 (52.9%) men with a mean age of 43 yr. The average follow-up time was 5.9 yr. In patients with SCD, SA provided significant improvements in VAS pain (9.1-3.8; P < .001), FE (95°-128°; P < .001), ER (24°-38°; P < .001), IR score (3.2-5.2; P < .001), FE strength (4.2-4.8; P < .001), ER strength (4.1-4.7; P < .001), IR strength (4.1-4.7; P < .001), and American Shoulder and Elbow Surgeons scores (48.6-73.5; P < .001). When compared to the matched cohort, the SCD group demonstrated higher preoperative (9.1 vs. 3.8; P < .001) and postoperative VAS scores (3.8 vs. 1.3; P < .001). Other clinical outcomes demonstrated no significant differences. There were 5 (29%) complications, 2 (11.8%) episodes of sickle cell crisis, and 3 (18%) reoperations in the SCD cohort. When compared to the matched cohort, there were no statistical differences with respect to complications (29% vs. 12%; P = .140) or reoperations (18% vs. 12%; P = .387). CONCLUSIONS: SA is an effective treatment modality for glenohumeral AVN in patients with SCD. Patients may expect improvements in pain, function, motion, and strength. However, final postoperative pain relief may be less than those treated with SA without SCD. Unique perioperative management is necessary to mitigate the risk of postoperative sickle cell crises.

Concurrent targeting of glycolysis in bacteria and host cell inflammation in septic arthritis.

Intracellular infiltration of bacteria into host cells complicates medical and surgical treatment of bacterial joint infections. Unlike soft tissue infections, septic arthritis and infection-associated inflammation destroy cartilage that does not regenerate once damaged. Herein, we show that glycolytic pathways are shared by methicillin-resistant Staphylococcus aureus (MRSA) proliferation and host inflammatory machinery in septic arthritis. MRSA readily penetrates host cells and induces proinflammatory cascades that persist after conventional antibiotic treatment. The glycolysis-targeting drug dimethyl fumarate (DMF) showed both bacteriostatic and anti-inflammatory effects by hindering the proliferation of intracellular MRSA and dampening excessive intraarticular inflammation. Combinatorial treatment with DMF and vancomycin further reduced the proliferation and re-emergence of intracellular MRSA. Combinatorial adjuvant administration of DMF with antibiotics alleviated clinical symptoms of septic arthritis by suppressing bacterial burden and curbing inflammation to protect cartilage and bone. Our results provide mechanistic insight into the regulation of glycolysis in the context of infection and host inflammation toward development of a novel therapeutic paradigm to ameliorate joint bioburden and destruction in septic arthritis.

Enhancement of Impaired MRSA-Infected Fracture Healing by Combinatorial Antibiotics and Modulation of Sustained Inflammation.

Fracture healing is impaired in the setting of infection, which begets protracted inflammation. The most problematic causative agent of musculoskeletal infection is methicillin-resistant Staphylococcus aureus (MRSA). We hypothesized that modulation of excessive inflammation combined with cell-penetrating antibiotic treatments facilitates fracture healing in a murine MRSA-infected femoral fracture model. Sterile and MRSA-contaminated open transverse femoral osteotomies were induced in 10-week-old male C57BL/6 mice and fixed via intramedullary nailing. In the initial therapeutic cohort, empty, vancomycin (V), rifampin (R), vancomycin-rifampin (VR), or vancomycin-rifampin-trametinib (VRT) hydrogels were applied to the fracture site intraoperatively. Rifampin was included because of its ability to penetrate eukaryotic cells to target intracellular bacteria. Unbiased screening demonstrated ERK activation was upregulated in the setting of MRSA infection. As such, the FDA-approved mitogen-activated protein kinase kinase (MEK)1-pERK1/2 inhibitor trametinib was evaluated as an adjunctive therapeutic agent to selectively mitigate excessive inflammation after infected fracture. Two additional cohorts were created mimicking immediate and delayed postoperative antibiotic administration. Systemic vancomycin or VR was administered for 2 weeks, followed by 2 weeks of VRT hydrogel or oral trametinib therapy. Hematologic, histological, and cytokine analyses were performed using serum and tissue isolates obtained at distinct postoperative intervals. Radiography and micro-computed tomography (µCT) were employed to assess fracture healing. Pro-inflammatory cytokine levels remained elevated in MRSA-infected mice with antibiotic treatment alone, but increasingly normalized with trametinib therapy. Impaired callus formation and malunion were consistently observed in the MRSA-infected groups and was partially salvaged with systemic antibiotic treatment alone. Mice that received VR alongside adjuvant MEK1-pERK1/2 inhibition displayed the greatest restoration of bone and osseous union. A combinatorial approach involving adjuvant cell-penetrating antibiotic treatments alongside mitigation of excessive inflammation enhanced healing of infected fractures. © 2022 American Society for Bone and Mineral Research (ASBMR).

Biomechanical restoration of metastatic cancer-induced peri-acetabular bone defects by ablation-osteoplasty-reinforcement-internal fixation technique (AORIF): To screw or not to screw?

BACKGROUND: Minimally invasive percutaneous polymethyl methacrylate cement augmentation procedures offer numerous clinical advantages for patients with periacetabular osteolytic metastatic bone defects in contrast to open reconstructive procedures that are associated with many complications. Several techniques, such as Ablation-Osteoplasty-Reinforcement-Internal Fixation (AORIF), cementoplasty alone, and screw fixation alone are currently used. There is no consensus on optimal skeletal reinforcement of diseased bones. The purpose of this study was to determine the most effective technique of percutaneous acetabular augmentation for joint preservation, with respect to resilience on cyclic loading and fracture pattern at maximal load to failure. METHODS: Five cohorts of hemipelvis composite bones with uniform periacetabular defects and various types of reinforcement techniques were utilized to simulate osteolytic metastasis in the weight bearing dome of the acetabulum. Five groups of hemipelves underwent finite element analysis and biomechanical testing for load to failure, energy absorption to failure, stress relaxation on cyclic loading, and fracture locations. RESULTS: The combination of screws and bone cement augmentation demonstrated significant higher energy absorption than the cement or screw only groups (p < 0.05), and better protection of acetabulum from displaced intraarticular fractures than the screws alone oror cement only groups (p < 0.05). Resilience to cyclic loading was higheest in the screw with cement fixation group than the screw only repair (p < 0.01), though not the cement fixation only group. INTERPRETATION: These data support the hypothesis that cementoplasty combined with screw augmentation such as the AORIF technique provides the best protection of acetabulum from massive metastatic cancer-induced acetabular fractures compared to augmentation with screws or cement alone.

Association of Demographic Factors and Medical School Experiences With Students' Intention to Pursue a Surgical Specialty and Practice in Underserved Areas.

Importance: The surgical workforce shortage is a threat to promoting health equity in medically underserved areas. Although the Health Resources and Services Administration and the American College of Surgeons have called to increase the surgical pipeline for trainees to mitigate this shortage, the demographic factors associated with students' intention to practice in underserved areas is unknown. Objective: To evaluate the association between students' demographics and medical school experiences with intention to pursue surgery and practice in underserved areas. Design, Setting, and Participants: This cross-sectional study surveyed graduating US allopathic medical students who matriculated between 2007-2008 and 2011-2012. Analysis began June 2020 and ended December 2020. Main Outcomes and Measures: Intention to pursue surgery and practice in underserved areas were retrieved from the Association of American Medical Colleges graduation questionnaire. Logistic regression models were constructed to evaluate (1) the association between demographic factors and medical students' intention to pursue surgical specialties vs medical specialties and (2) the association between demographic factors and medical school electives with intention to practice in underserved areas. Results: Among 57 307 students who completed the graduation questionnaire, 48 096 (83.9%) had complete demographic data and were included in the study cohort. The mean (SD) age at matriculation was 23.4 (2.5) years. Compared with students who reported intent to pursue nonsurgical careers, a lower proportion of students who reported intent to pursue a surgical specialty identified as female (3264 [32.4%] vs 19 731 [51.9%]; χ2 P < .001). Multiracial Black and White students (adjusted odds ratio [aOR], 1.72; 95% CI, 1.11-2.65) were more likely to report an intent for surgery compared with White students. Among students who reported an intention to pursue surgery, Black/African American students (aOR, 3.24; 95% CI, 2.49-4.22), Hispanic students (aOR, 2.00; 95% CI, 1.61-2.47), multiracial Black and White students (aOR, 2.27; 95% CI, 1.03-5.01), and Indian/Pakistani students (aOR, 1.31; 95% CI, 1.02-1.69) were more likely than White students to report an intent to practice in underserved areas. Students who reported participating in community health (aOR, 1.61; 95% CI, 1.42-1.83) or global health (aOR, 1.83; 95% CI, 1.61-2.07) experiences were more likely to report an intention to practice in underserved areas. Conclusions and Relevance: This study suggests that diversifying the surgical training pipeline and incorporating health disparity and community health in undergraduate or graduate medical education may promote students' motivation to practice in underserved areas.

Inflammatory conversion of quiescent osteoblasts by metastatic breast cancer cells through pERK1/2 aggravates cancer-induced bone destruction.

Disruption of bone homeostasis caused by metastatic osteolytic breast cancer cells increases inflammatory osteolysis and decreases bone formation, thereby predisposing patients to pathological fracture and cancer growth. Alteration of osteoblast function induces skeletal diseases due to the disruption of bone homeostasis. We observed increased activation of pERK1/2 in osteolytic breast cancer cells and osteoblasts in human pathological specimens with aggressive osteolytic breast cancer metastases. We confirmed that osteolytic breast cancers with high expression of pERK1/2 disrupt bone homeostasis via osteoblastic ERK1/2 activation at the bone-breast cancer interface. The process of inflammatory osteolysis modulates ERK1/2 activation in osteoblasts and breast cancer cells through dominant-negative MEK1 expression and constitutively active MEK1 expression to promote cancer growth within bone. Trametinib, an FDA-approved MEK inhibitor, not only reduced breast cancer-induced bone destruction but also dramatically reduced cancer growth in bone by inhibiting the inflammatory skeletal microenvironment. Taken together, these findings suggest that ERK1/2 activation in both breast cancer cells and osteoblasts is required for osteolytic breast cancer-induced inflammatory osteolysis and that ERK1/2 pathway inhibitors may represent a promising adjuvant therapy for patients with aggressive osteolytic breast cancers by altering the shared cancer and bone microenvironment.

Dual therapeutic targeting of intra-articular inflammation and intracellular bacteria enhances chondroprotection in septic arthritis.

Bacterial infections involving joints and vital organs represent a challenging clinical problem because of the two concurrent therapeutic goals of bacterial eradication and tissue preservation. In the case of septic arthritis, permanent destruction of articular cartilage by intense host inflammation is commonly seen even after successful treatment of bacterial infection. Here, we provide scientific evidence of a novel treatment modality that can protect articular cartilage and enhanced eradication of causative bacteria in septic arthritis. Locally delivered cell-penetrating antibiotics such as rifampicin effectively eradicate intracellular reservoirs of methicillin-resistant Staphylococcus aureus within joint cells. Furthermore, mitigation of intra-articular inflammation by targeting the NLRP3 (nucleotide-binding oligomerization domain-, leucine-rich repeat- and pyrin domain-containing 3) inflammasome protects articular cartilage from damage in a murine model of knee septic arthritis. Together, concurrent mitigation of intra-articular inflammation and local adjuvant targeting of intracellular bacteria represents a promising new therapeutic strategy for septic arthritis.

Predictors and Sequelae of Postoperative Delirium in a Geriatric Patient Population With Hip Fracture.

INTRODUCTION: Postoperative delirium is common for patients with hip fracture. Predictors of postoperative delirium and its association with preexisting dementia and adverse postoperative outcomes in a geriatric hip fracture population were assessed. METHODS: Patients with hip fracture aged 60 years and older were identified in the 2016 and 2017 National Surgical Quality Improvement Program Procedure Targeted Databases. Independent risk factors of postoperative delirium were identified. Associations with mortality, readmission, and revision surgery were evaluated using moderation and mediation analysis. RESULTS: Of 18,754 patients with hip fracture, 30.2% had preoperative dementia, 18.8% had postoperative delirium, and 8.3% had both preoperative dementia and postoperative delirium. Independent predictors of postoperative delirium were as follows: older age, male sex, higher American Society of Anesthesiologists score, dependent functional status, nongeneral anesthesia, preoperative diabetes, bleeding disorder, and preoperative dementia. Preoperative dementia and postoperative delirium each had an independent correlation with 30-day mortality (odds ratios = 2.06 and 1.92, respectively, with P < 0.001 for both). However, when both were present, those with preoperative dementia and postoperative delirium had an even higher odds of mortality based on moderation analysis (odds ratio = 2.25, P < 0.001). Readmissions and reoperations were significantly correlated with postoperative delirium, but not with preoperative dementia. The combination of preoperative dementia and postoperative delirium, however, did have compounding effects. Furthermore, a significant proportion of the total effect of preoperative dementia on mortality and readmission was accounted for by the development of postoperative delirium based on mediation analysis (medeff: 7%, P < 0.001 and medeff: 35%, P < 0.001). DISCUSSION: Postoperative delirium is a potentially preventable postoperative adverse outcome that was seen in 18.8% of 18,754 patients with hip fracture. Those with preoperative dementia seem to be a particularly at-risk subpopulation. Quality improvement initiatives to minimize postoperative delirium in this hip fracture population should be considered and optimized.

Ablation, Osteoplasty, Reinforcement, and Internal Fixation for Percutaneous Endoskeletal Reconstruction of Periacetabular and Other Periarticular Osteolytic Metastases.

For osteolytic metastatic disease in the pelvis and acetabulum of patients with unpredictable and limited lifespans, first-line treatment focuses on targeting the primary cancer with anticancer drugs, osteoclastogenesis inhibitors, analgesics, and radiation therapy. Uncontrolled pain and progressive bone destruction refractory to these interventions often warrant surgical stabilization. Conventional open surgical procedures using metal implants or prostheses may provide immediate biomechanical stability but are associated with various complications without local cancer control. Outcomes of conventional open surgical reconstructive procedures depend on local cancer progression and progressive bone loss. Percutaneous cancer ablation and bone augmentation with polymethyl methacrylate cement alone often lack optimal internal fixation and integration with surrounding bone. The current literature demands a multipurpose minimally invasive surgical intervention that provides local cancer control, bone protection, and stabilization. An overview of new, alternative percutaneous procedure consisting of image-guided ablation, balloon osteoplasty, cement reinforcement, and internal fixation, which offers a minimally invasive percutaneous treatment option for patients with osteolytic metastatic cancers with the advantages of concurrent thermal necrotization of cancers, zoledronate-loaded bone cementoplasty, and surgical stabilization in an ambulatory surgery setting, is warranted. Early clinical results have shown that the ablation, balloon osteoplasty, cement reinforcement, and internal fixation is a safe and effective alternative solution for stabilizing and palliating osteolytic lesions in patients seeking new effective therapies in the era of rapidly evolving oncologic care.

Smoking Alters Inflammation and Skeletal Stem and Progenitor Cell Activity During Fracture Healing in Different Murine Strains.

Smokers are at a higher risk of delayed union or nonunion after fracture repair. Few specific interventions are available for prevention because the molecular mechanisms that result in these negative sequelae are poorly understood. Murine models that mimic fracture healing in smokers are crucial in further understanding the local cellular and molecular alterations during fracture healing caused by smoking. We exposed three murine strains, C57BL/6J, 129X1/SvJ, and BALB/cJ, to cigarette smoke for 3 months before the induction of a midshaft transverse femoral osteotomy. We evaluated fracture healing 4 weeks after the osteotomy using radiography, micro-computed tomography (µCT), and biomechanical testing. Radiographic analysis demonstrated a significant decrease in the fracture healing capacity of smoking 129X1/SvJ mice. µCT results showed delayed remodeling of fracture calluses in all three strains after cigarette smoke exposure. Biomechanical testing indicated the most significant impairment in the functional properties of 129X1/SvJ in comparison with C57BL/6J and BALB/cJ mice after cigarette smoke exposure. Thus, the 129X1/SvJ strain is most suitable in simulating smoking-induced impaired fracture healing. Furthermore, in smoking 129X1/SvJ murine models, we investigated the molecular and cellular alterations in fracture healing caused by cigarette smoking using histology, flow cytometry, and multiplex cytokine/chemokine analysis. Histological analysis showed impaired chondrogenesis in cigarette smoking. In addition, the important reparative cell populations, including skeletal stem cells and their downstream progenitors, demonstrated decreased expansion after injury as a result of cigarette smoking. Moreover, significantly increased pro-inflammatory mediators and the recruitment of immune cells in fracture hematomas were demonstrated in smoking mice. Collectively, our findings demonstrate the significant cellular and molecular alterations during fracture healing impaired by smoking, including disrupted chondrogenesis, aberrant skeletal stem and progenitor cell activity, and a pronounced initial inflammatory response. © 2020 American Society for Bone and Mineral Research (ASBMR).

Locally delivered adjuvant biofilm-penetrating antibiotics rescue impaired endochondral fracture healing caused by MRSA infection.

Infection is a devastating complication following an open fracture. We investigated whether local rifampin-loaded hydrogel can combat infection and improve healing in a murine model of methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis. A transverse fracture was made at the tibia midshaft of C57BL/6J mice aged 10-12 weeks and stabilized with an intramedullary pin. A total of 1 × 106 colony-forming units (CFU) of MRSA was inoculated. A collagen-based hydrogel containing low-dose (60 µg) and high-dose (300 µg) rifampin was applied before closure. Postoperative treatment response was assessed through bacterial CFU counts from tissue and hardware, tibial radiographs and microcomputed tomography (µCT), immunohistochemistry, and histological analyses. All untreated MRSA-infected fractures progressed to nonunion by 28 days with profuse MRSA colonization. Infected fractures demonstrated decreased soft callus formation on safranin O stain compared to controls. Areas of dense interleukin-1ß stain were associated with poor callus formation. High-dose rifampin hydrogels reduced the average MRSA load in tissue (p < 0.0001) and implants (p = 0.041). Low-dose rifampin hydrogels reduced tissue bacterial load by 50% (p = 0.021). Among sterile models, 88% achieved union compared to 0% of those infected. Mean radiographic union scale in tibia scores improved from 6 to 8.7 with high-dose rifampin hydrogel (p = 0.024) and to 10 with combination local/systemic rifampin therapy (p < 0.0001). µCT demonstrated reactive bone formation in MRSA infection. Histology demonstrated restored fracture healing with bacterial elimination. Rifampin-loaded hydrogels suppressed osteomyelitis, prevented implant colonization, and improved healing. Systemic rifampin was more effective at eliminating infection and improving fracture healing. Further investigation into rifampin-loaded hydrogels is required to correlate these findings with clinical efficacy.