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Abstract Bone marrow is the primary immune organ responsible for stem cell maintenance and hematopoiesis. However, the contribution of the bone marrow niche for the generation of adaptive immune responses is less well-understood. We therefore assessed the capacity of virus antigen-specific CD8 T cells to be generated and expanded in bone marrow following acute neurotropic virus infection. Intracranial infection with the neurotropic Theiler’s Murine Encephalomyelitis Virus (TMEV) results in an acute infection in the C57BL/6 mouse which is cleared within 4 weeks post infection due to the generation of an antigen-specific CD8 T cell response against the immunodominant epitope VP2 121-130 . We determined that 1-10% of CD8 T cells present in the femoral, and sternal bone marrow were virus antigen-specific 5-7 days after intracranial TMEV infection. We determined that antigen-specific CD8 T cells were generated in the bone marrow with similar kinetics to that of conventional responses in the secondary lymphoid organs. Importantly, continuous treatment with FTY720, which sequesters T cells outside of the blood, did not eliminate antigen-specific CD8 T cells in the bone marrow compartment indicating generation within the bone marrow niche. Similarly, injection of Poly I:C admixed with fluorescently labeled ovalbumin into the brain generated a similar antigen-specific CD8 T cell response in the bone marrow indicating these responses occur following various brain insults. This model also identified the likely antigen presenting cell (APC) responsible for scavenging antigens from the brain and trafficking into the bone marrow as a migratory myeloid-derived APC. Moreover, following clearance of TMEV infection, CD8 T cells in the bone marrow established durable memory. Antigen-specific memory CD8 T cells in the bone marrow reactivated and expanded upon cognate antigen reencounter. Antigen-specific reactivation of memory CD8 T cells within the bone marrow caused a concurrent increase in Lineage-, Sca-1+, c-Kit+ (LSK) and CD11b+ MHCII+ myeloid cells. This increase in the LSKs and myeloid cells in the bone marrow niche was abrogated with CD8 T cell depletion. We conclude that brain viral infections induce in situ effector and memory T cell responses within the bone marrow compartment. Memory recall CD8 T cell responses induce niche dysregulation by expanding LSK cells and lead to an influx of MHCII+ myeloid cells. Our data pave the way for crucial studies of bone marrow resident antigen-specific CD8 T cells in health and diseases.

Study Design. Modified Delphi consensus process Objective. To establish a standardized, consensus-driven definition for postoperative spine infection (PSI) for research, diagnosis, and management. Summary of Background Data. Postoperative infection is a devastating and common complication following spine surgery. Rates of PSI in the literature range from 0% to over 20% depending on surgical indication and invasiveness. Despite the implications of PSI, there is no universally accepted diagnostic standard or consensus definition for infection following spine surgery, hindering research and treatment of this challenging clinical condition. Methods. A multispecialty workgroup convened by the Musculoskeletal Infection Society (MSIS) conducted a systematic literature review. Using data from the systematic review, an expert panel completed a modified Delphi process to achieve consensus. The panel included nine fellowship-trained, board-certified physicians with expertise in infectious diseases, orthopaedic and neurologic spine surgery, and musculoskeletal radiology. Iterative rounds focused on criterion selection, importance ranking, categorical grouping, and final constellation development for PSI diagnosis. Consensus was defined as a 2/3 majority, with a target of 100%. Results. The workgroup achieved 100% consensus on a new PSI definition, which incorporates six clinical domains: wound features, microbiology, imaging, inflammatory biomarkers, intraoperative findings, and histology. A single microbiological stand-alone criterion—identification of a phenotypically indistinguishable organism from two or more deep operative site specimens—was established as pathognomonic for postoperative spine infection. Additional primary and secondary supporting criteria were defined, with specific combinations required to classify cases as definite or probable PSI. Final definitions were ratified by the boards of MSIS and the European Bone & Joint Infection Society (EBJIS) Conclusion. This consensus-based definition provides a standardized framework for diagnosing postoperative spine infection, facilitating research and clinical management. The criteria balance sensitivity and specificity across diverse clinical scenarios and represent the first multispecialty, society-endorsed definition for PSI.

Abstract Purpose Acetabular overcoverage (pincer morphology) has been suggested to be both a source of pain and dysfunction as well as potentially protective against osteoarthritic change. The purpose of this study was to compare minimum 5-year clinical outcomes of patients undergoing primary hip arthroscopic labral repair with a lateral center edge angle (LCEA) of ≥ 40° as compared to non-dysplastic controls with an LCEA of 25-40°. Methods We identified all patients that underwent primary hip arthroscopy with labral repair between 2009-2019 at a single academic institution. Patients with LCEA ≥ 40° (pincer) were propensity matched to non-dysplastic controls with LCEA 25-40° on a 1:2 basis by sex, age, body mass index (BMI), and year of surgery. Patient-reported outcome measures (PROMs) including Visual Analog Scale (VAS) for pain, Tegner activity score, modified Harris Hip Score (mHHS), International Hip Outcome Tool (iHOT-12), and Hip Outcome Score (HOS) were analyzed, as were reoperations and conversions to total hip arthroplasty (THA). Results Fifty-five patients with pincer morphology (mean preoperative LCEA: 41.9°, Tonnis angle: -7.3°, alpha angle: 58.8°) were matched to 110 non-dysplastic controls (LCEA: 31.2°, Tonnis angle: 2.2°, alpha angle: 58.9°), resulting in a total of 165 hips in 163 patients (67% females, mean age: 37.7 years, BMI: 26.8 kg/m2). Pincer patients were corrected to a mean postoperative LCEA of 38.7° (p<0.0001), with 22 pincer patients having residual overcoverage, namely a postoperative LCEA ≥ 40° (range: 40.0-45.8°). At mean 7.8 years follow-up (range: 5.1-13.2), there was no difference in any postoperative PROMs between pincers and controls (p>0.15) and no difference in PROMs between patients with residual overcoverage and pincer patients with a postoperatively normalized LCEA (p>0.25). At final follow-up, 4 patients in the pincer cohort (7%) and 21 controls (19%) had converted to THA (p=0.046). Conclusion Patients with lateral acetabular overcoverage demonstrated similar and satisfactory postoperative PROMs at a minimum of 5-year follow-up compared to propensity-matched non-dysplastic controls, regardless of if the LCEA was corrected to <40°. Of note, non-dysplastic controls demonstrated an increased rate of conversion to THA, supporting the potentially chondroprotective role of acetabular overcoverage.

Abstract Introduction Understanding factors that impact outcomes of total hip arthroplasty (THA) can aid clinical decision-making and patient counselling. The purpose of this study was to investigate functional outcomes, complications, and reoperation rates among patients undergoing primary THA after hip arthroscopy (HA-THA) compared to a matched cohort of primary THA patients without prior arthroscopy (THA-only). Methods A retrospective review was performed to identify all patients who underwent primary THA after prior hip arthroscopy from 2009-2022 at a single institution. Patients with a history of revision arthroscopy were excluded. Cases were propensity-matched with primary THA controls in a 1:4 ratio by age at time of THA, sex, body mass index, surgical approach, and year of surgery. At minimum 2-year follow-up, patient-reported outcomes (PROs) including Forgotten Joint Score (FJS), Modified Harris Hip Score (mHHS), Hip Disability and Osteoarthritis Outcome Score Pain (HOOS pain), and Visual Analog Pain Scale (VAS) were analyzed. Results Sixty-three hips in 60 patients (age: 47.3±9.4 years, BMI: 29.8±6.2 kg/m2) were matched to 252 THA-only hips, with patients converting to THA at a mean 3.1 years (range 0.3-10.3) following hip arthroscopy. While both HA-THA and THA patients demonstrated significant (p<0.001) postoperative improvements in PROs, HA-THA patients reported significantly lower postoperative FJS, mHHS, HOOS pain, and VAS pain scores (p<0.001) as compared to THA-only controls. At mean 6.6±3.2 years follow-up, HA-THA patients with preoperative Tönnis grades 2-3 reported significantly increased FJS, mHHS, and HOOS pain compared to those with preoperative Tönnis grades of 0-1 (p≤0.03). Additionally, HA-THA patients with preoperative Tönnis grades 0-1 exhibited worse PROs (p<0.001) as compared to THA-only controls. While there were no differences in complication rates between HA-THA patients and THA-only controls (8% vs. 5%, p=0.49), all-cause reoperation was greater amongst HA-THA patients compared to THA-only (10% vs. 2%, p=0.01). Conclusion While improved compared to preoperatively, patients undergoing THA after prior hip arthroscopy demonstrated inferior outcomes at mid-term follow up as compared to a demographically age-matched cohort without prior arthroscopy. When considering conversion to THA following arthroscopy, clinicians should consider counseling patients regarding improved outcomes in the setting of advanced radiographic osteoarthritis, and potentially increased all-cause reoperation.

Abstract Background Femoral version plays a critical role in pre-arthritic hip pain, particularly in femoroacetabular impingement (FAI). Variations in femoral version may contribute to hip instability or impingement. This study examines the outcomes of hip arthroscopy for FAI across different femoral version groups. Methods A prospective multicenter cohort of 677 FAI patients undergoing primary hip arthroscopy was collected, with 603 patients in this study based on recorded femoral version. Inclusion criteria were patients aged 14-45 years with idiopathic FAI, while previous ipsilateral hip procedures, associated disorders, or Tönnis 2 or greater osteoarthritis were excluded. Femoral version was measured on low-dose computed tomography (CT) utilizing the Yoshioka oblique method and categorized into five subgroups: <5°, 6°-15°, 16°-25°, 26°-35°, 35°+. Patient-reported outcomes (PROs) were obtained at minimum one-year follow-up. The modified Harris hip score (mHHS) was assessed relative to minimal clinically important difference (MCID) of 8 and patient acceptable symptom state (PASS) of 74. Additional PROs included HOOS Pain and Sports/Recreation subscores and iHOT-12 score. Composite failure was defined as reoperation for persistent symptoms or failure to achieve either the mHHS MCID or PASS. Results Males had statistically lower femoral version than females (14.0 vs 18.0; p<0.001). In females, 38.0% had a femoral version of 16°-25°, 17.9% between 26°-35°, and 3.6% greater than 35°, compared to 27.6%, 9.2%, and 1.8% in males, respectively (all p<0.001). Increased or decreased femoral versions appear to have similar outcomes to normal version. The mildly increased femoral anteversion groups of 16°-25° and 26°-35° demonstrated the best outcomes with changes in HOOS pain and sports subscores being significantly higher. Severely increased femoral anteversion, >35°, only present in 2.8% of patients, demonstrated a higher composite failure rate (15.4%) compared to moderately increased, 26°-35°, femoral version (3.1%). The decreased femoral version group, ≤5°, had a composite failure of 10.4% compared to normal femoral version, 16°-25° (10.2%). Conclusions The general anatomy differences between males and females lends males to be more in retroversion while females tend to be more anteverted. Overall, outcomes did not seem to differ between increased or decreased femoral versions but were superior at mildly increased femoral versions.

Objective The incidence of hip osteoarthritis (OA) is increasing with the aging population, leading to interest in intra-articular orthobiologic injections to alleviate symptoms and potentially slow disease progression. This systematic review aims to evaluate the clinical outcomes associated with six orthobiologic therapies for hip OA: hyaluronic acid (HA), platelet-rich plasma (PRP), autologous cells therapy (ACT), microfragmented adipose tissue (MFAT), and bone marrow aspirate (BMA) and its concentration (BMAC). Methods We conducted a literature search according to the PRISMA guidelines. Studies were included in our review if they used at least one of the four orthobiologic therapies and reported on the clinical outcome using patient reported outcome measures (PROMs). Since there is a large variability among clinical outcomes, we focused on the three most utilized PROMs (VAS, WOMAC, and HHS) and the latest follow-up time point. Results Of the 716 studies reviewed, thirty-six studies (n=36) fit inclusion criteria. There were 21 studies examining HA, 11 on PRP, 3 for MFAT, 2 for ACT, and 3 on BMA/BMAC. Eight studies were randomized controlled trials and 28 were cohort studies. The mean age of the patient population ranged from 45 ± 17.0 to 74 ± 8.0. The baseline grade of osteoarthritis ranged from 1-4 but was most reported as moderate (2-3). Overall, there was an improvement in PROMs at the latest follow-up after receiving orthobiologic interventions. Discussion Orthobiologic injections have shown promise for improving PROMs in patients with hip OA. Future studies should evaluate long-term efficacy and include randomized trials to establish efficacy.

An ST-segment elevation myocardial infarction is a life-threatening condition within the spectrum of acute coronary syndrome, with well-recognized implications for short-term and long-term health outcomes. Retrospective review of our institutional electronic health records identified patterns of inaccurate acute coronary syndrome diagnostic assignment, including the presence of erroneous ST-segment elevation myocardial infarction diagnoses in discharge records. Such erroneous diagnoses in the durable health record may increase risk to patients through inadequate risk assessment and inappropriate follow-up care. Misapplication of a shortcut in our electronic health record system for rapidly ordering emergent cases was identified as a potential cause of the quality gap. To address this issue, a nurse-led quality improvement project was developed by using the define, measure, analyze, improve, and control framework. The project intervention decreased the percentage of patients with erroneous diagnoses from 24% to 7% and marginally improved nursing staff satisfaction. Our project successfully addressed an institutional quality concern. Our goal of reducing erroneous discharge diagnoses with minimal disruption to our existing practice was achieved, positively affecting our patients. Including both nurse leaders and frontline health care workers ensured the success of our project.

Background: Among the 1.5 million cases of cutaneous squamous cell carcinoma (cSCC) diagnosed annually in the United States, a subset of aggressive tumors recur or metastasize. Treatment options include total margin-controlled surgery, such as Mohs micrographic surgery or other forms of peripheral and deep en face margin assessment (MMS/PDEMA), and standard excision with postoperative vertical section margin assessment (SEVMA). NCCN Guidelines recommend MMS/PDEMA for the management of cSCC classified as very high risk based on NCCN risk stratification criteria. This study aims to validate the recommendation of MMS/PDEMA as the preferred surgical approach for NCCN very high-risk cSCCs, using data from a multicenter, multinational cohort. Methods: A multicenter cohort study was conducted across 12 sites, including 10 in the United States, 1 in Spain, and 1 in Brazil, comprising 2,752 primary NCCN very high-risk cSCCs treated with MMS/PDEMA or SEVMA. Propensity score–weighted analysis was used to balance baseline characteristics. Outcomes included local recurrence (LR), nodal metastasis (NM), distant metastasis (DM), and disease-specific death (DSD). Results: After balancing baseline characteristics, SEVMA was associated with a 2-fold higher rate of poor outcomes, including recurrence, metastasis, and DSD, compared with MMS/PDEMA. The 3-year cumulative incidence of poor outcomes was higher for SEVMA: LR (12.5% vs 5.9%), NM (11.6% vs 6.0%), DM (4.3% vs 1.9%), and DSD (6.2% vs 3.3%). Conclusions: This study supports the NCCN recommendation of MMS/PDEMA for NCCN very high-risk cSCC, showing reduced recurrence, metastasis, and cSCC-specific mortality compared with SEVMA.

Abstract Background 0.05% Chlorhexidine gluconate (CHG) is now commonly used as an antiseptic irrigation for inflatable penile prosthesis (IPP) surgery. Limited in vitro data suggest compatibility of 0.05% CHG with antibiotic impregnated IPP devices; however, very little clinical research exists to guide use of 0.05% CHG in this population. Aim Assess the relationship of 0.05% CHG and antibiotic impregnated IPP infection in a large multi-institutional cohort. Methods We retrospectively reviewed a multi-institutional cohort of patients who underwent antibiotic impregnated IPP implantation. We identified cases using intraoperative 0.05% CHG and an equal number of consecutive control cases without 0.05% CHG use from each center for comparison. The primary outcome was IPP infection requiring explantation. Patient demographics and surgical variables were analyzed using chi-square tests and multivariable logistic regression to identify variables associated with infection. Outcomes The primary outcome was IPP infection requiring device explanation. Results Among 14 participating institutions, 761 cases using an antibiotic impregnated IPP were analyzed. Of these, 348 (45.7%) had 0.05% CHG used during the case. Median follow-up was 4 months (interquartile range 1-12) for the 0.05% CHG group and 8 months (interquartile range 2-21) for the control group. Intraoperative 0.05% CHG utilization was not associated with antibiotic impregnated IPP infection rate (1.9% vs. 2.0%, P = .9). On multivariable analysis, prior IPP infection (OR 6.32, 95% CI 1.32-30.2, P = .021) and prior priapism (OR 10.01, 95% CI 1.18-89.7, P = .039) were associated with increased infection risk. Clinical implications The use of 0.05% CHG irrigation with antibiotic impregnated IPPs was associated with similar infection rates compared to antibiotic irrigation. Strengths and limitations Limitations include the use of a historical comparator cohort which may introduce unknown confounders, practice variation between multiple sites, shorter follow-up in the 0.05% CHG cohort, and the low incidence of IPP infection which may limit statistical power despite a large sample. The major strengths include the large, multi-institutional cohort, and the use of consecutive patients to minimize selection bias. Conclusion 0.05% CHG utilization was not associated with infection rates in antibiotic impregnated IPPs.