A Pilot Study of Pembrolizumab Combined With Stereotactic Ablative Radiotherapy for Patients With Advanced or Metastatic Sarcoma.

OBJECTIVES: Immunotherapy with immune checkpoint inhibitors has shown only limited success in the management of metastatic soft tissue sarcoma. Overall response rates (ORR) with single agent pembrolizumab were 18% and median PFS was 18 weeks on the clinical trial SARC028. One strategy to improve the responses to immunotherapy is with stereotactic body radiation therapy (SBRT), which can enhance the antitumor CD8 T cell response through the release of tumor-specific antigens, potentially priming a more diverse class of T cell receptors. METHODS: This is a phase 0, pilot prospective study taking place at a single center with 2 arms. In Arm A, patients are treated with pembrolizumab 400 mg IV infusion on day 1 of a 42-day cycle. Stereotactic body radiation therapy (SBRT) is delivered in 1-5 fractions starting on C1D15-28 and given every other day. In Arm B, patients who have started an immune checkpoint inhibitor within 60 days are treated with SBRT in addition to the current therapy. RESULTS: In this study we outline testing the feasibility of adding SBRT to pembrolizumab. CONCLUSION: The ultimate goal of combination therapy is improved overall response, including tumors not treated with SBRT. This trial can be found registered online: NCT05488366.

The Correlation Between Lymphocyte Nadir and Radiation Therapy for Soft Tissue Sarcoma: Defining Key Dosimetric Parameters and Outlining Clinical Significance.

Purpose: The objectives of this study were to identify key dosimetric parameters associated with postradiation therapy lymphopenia and uncover any effect on clinical outcomes. Methods and Materials: This was a retrospective review of 69 patients (between April 2010 and January 2023) who underwent radiation therapy (RT) as a part of curative intent for soft tissue sarcoma (STS) at a single academic institution. All patients with treatment plans available to review and measurable absolute lymphocyte count (ALC) nadir within a year after completion of RT were included. Results: Median follow-up was 22 months after the start of RT. A decrease in lymphocyte count was noted as early as during treatment and persisted at least 3 months after the completion of RT. On multivariable linear regression, the strongest correlations with ALC nadir were mean body dose, body V10 Gy, mean bone dose, bone V10 Gy, and bone V20 Gy. Five-year overall survival was 60% and 5-year disease-free survival was 44%. Advanced T-stage, chemotherapy use, use of intensity-modulated RT, lower ALC nadir, and the development of grade ≥2 lymphopenia at nadir were associated with worse overall survival and disease-free survival. Conclusions: Post-RT lymphopenia was associated with worse outcomes in STS. There were associations between higher body V10 Gy and bone V10 Gy and lower post-RT ALC nadir, despite the varying sites of STS presentation, which aligns with the well-known radiosensitivity of lymphocyte cell lines. These findings support efforts to reduce treatment-related hematopoietic toxicity as a way to improve oncologic outcomes. Additionally, this study supports the idea that the effect of radiation on lymphocyte progenitors in the bone marrow is more significant than that on circulating lymphocytes in treatments with limited involvement of the heart and lung.

Risk factors for postoperative delirium in orthopaedic hip surgery patients: a database review.

BACKGROUND: Postoperative delirium is a common problem affecting admitted patients that decreases patient satisfaction and increases the cost and complexity of care. The purpose of this study was to use the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database to compare rates and risk factors of postoperative delirium for total hip arthroplasty (THA) and hemiarthroplasty patients indicated for osteoarthritis or proximal femur fracture. METHODS: The 2021 NSQIP database was queried for patients using Current Procedural Terminology (CPT) codes for THA and hemiarthroplasty and ICD-10 codes for osteoarthritis or proximal femur fracture. Demographic, past medical history, preoperative labs, and functional status data were recorded. Procedural data were also collected. Finally, postoperative outcomes and complications were reviewed. RESULTS: Overall, 16% of patients had postoperative delirium. Delirium patients were older on average (82.4 years vs. 80.7 years, p < 0.001), had a lower BMI (19.5 vs. 24.8, p < 0.001), were more likely to have a history of dementia (54.6% vs. 13.6%, p < 0.001), were less likely to have an independent functional status (p < 0.001) or live alone (p < 0.001), and were more likely to have sustained a recent fall (p < 0.001). Delirium patients were more likely to be hyponatremic or hypernatremic (p = 0.002), anemic (p < 0.001), and severely dehydrated (p < 0.001), among other lab abnormalities. Delirium patients were also more likely to experience additional postoperative complications, including pneumonia, pulmonary embolism, urinary tract infection, stroke, cardiac arrest, sepsis, and unplanned reoperation and readmission after discharge (all p < 0.05). CONCLUSIONS: In this study, factors associated with postoperative delirium in patients undergoing hemiarthroplasty and THA were identified, including older age, lower BMI, certain medical conditions, decreased functional status, certain lab abnormalities, and postoperative complications. These findings can be used by clinicians to better inform care and to determine when orthopaedic joint replacement patients may be at an increased risk for postoperative delirium.

Surgical management of a rare myxopapillary ependymoma of the gluteal region: A case report.

BACKGROUND: Ependymomas are rare tumors originating from neuroepithelial cells lining the wall of the ventricles or central canal of the spinal cord. While these tumors mainly occur within the central nervous system (CNS), there are occasional reports in children and young adult patients with a primary tumor occurrence outside of the CNS. Ependymomas of the sacrococcygeal region have been infrequently described in the literature with no standard of care established. We present a case report and review of the literature regarding this rare entity. CASE DESCRIPTION: A 24-year-old woman presented with right gluteal pain worsened by sitting and a palpable soft tissue mass of the sacrococcygeal region. Magnetic resonance imaging revealed a 3.7 cm cystic mass centered in the right gluteal region. She underwent a biopsy at an outside institution, with histology revealing myxopapillary ependymoma. The patient was referred to our hospital and underwent an interdisciplinary neurosurgical and orthopedic oncology en bloc resection of the ependymoma, which intraoperatively appeared to originate from the coccygeal nerve. CONCLUSION: In the present report, the authors demonstrate that a myxopapillary ependymoma may present as an isolated gluteal mass attached to the coccygeal nerve, without frank CNS involvement. Furthermore, an interdisciplinary approach to surgical resection of this lesion appears to represent an effective treatment modality.

Resident Participation in Fixation of Intertrochanteric Hip Fractures: Analysis of the NSQIP Database.

BACKGROUND: Future generations of orthopaedic surgeons must continue to be trained in the surgical management of hip fractures. This study assesses the effect of resident participation on outcomes for the treatment of intertrochanteric hip fractures. METHODS: The National Surgical Quality Improvement Program (NSQIP) database (2010 to 2013) was queried for intertrochanteric hip fractures (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] code 820.21) treated with either extramedullary (Current Procedural Terminology [CPT] code 27244) or intramedullary (CPT code 27245) fixation. Demographic variables, including resident participation, as well as primary (death and serious morbidity) and secondary outcome variables were extracted for analysis. Univariate, propensity score-matched, and multivariate logistic regression analyses were performed to evaluate outcome variables. RESULTS: Data on resident participation were available for 1,764 cases (21.0%). Univariate analyses for all intertrochanteric hip fractures demonstrated no significant difference in 30-day mortality (6.3% versus 7.8%; p = 0.264) or serious morbidity (44.9% versus 43.2%; p = 0.506) between the groups with and without resident participation. Multivariate and propensity score-matched analyses gave similar results. Resident involvement was associated with prolonged operating-room time, length of stay, and time to discharge when a prolonged case was defined as one above the 90th percentile for time parameters. CONCLUSIONS: Resident participation was not associated with an increase in morbidity or mortality but was associated with an increase in time-related secondary outcome measures. While attending surgeon supervision is necessary, residents can and should be involved in the care of these patients without concern that resident involvement negatively impacts perioperative morbidity and mortality. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Return to Sports Activity following UKA and TKA.

Unicompartmental medial knee arthritis can be successfully treated with either unicompartmental or total knee arthroplasty (UKA or TKA). Active patients often inquire about the relative likelihood of returning to a sport-related activity after surgery. Some advocates of UKA suggest that UKA can lead to a higher rate of return to sports activity postoperatively, but little information is available comparing the outcomes of UKA versus TKA. We identified 33 patients with UKA and 39 patients with TKA with minimum 2-year follow-up (4 ± 1.2 years) who had similar preoperative clinical and radiographic examinations. Clinical evaluation revealed no difference in the number of patients who returned to sports or their satisfaction, but patients with UKA returned to sports more quickly and exhibited better postoperative knee scores than TKA patients.

Preliminary validation of the Review of Musculoskeletal System (ROMS) questionnaire.

BACKGROUND: Measurement of clinical outcomes is necessary to define best practice. It requires a validated tool that can be easily applied as part of clinical practice. We present the preliminary validation of a brief self-reported Review of Musculoskeletal System (ROMS) questionnaire that captures functional limitations due to musculoskeletal problems and other medical and emotional conditions. METHODS: Data were derived from a clinical outcomes database (Orthopaedic Minimal Data Set [OrthoMiDaS]) that combines patient-reported data collected as part of routine care and secondary data extracted from electronic medical records. The study utilized 82,873 encounters collected from 24,116 consecutive patients with problems in the upper and lower extremities. In addition to the ROMS, the study used version 2 of the Short Form-12 (SF-12v2), the Penn Shoulder Score (PSS), the Hip disability and Osteoarthritis Outcome Score (HOOS), and the Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaires. Fifteen cross-sectional samples were used to evaluate the floor and ceiling effects as well as the construct and content validity. Five longitudinal cohorts were used to measure test-retest reliability and responsiveness. Standard statistical tests were applied. RESULTS: The floor and ceiling effects of the ROMS questionnaire in patients with shoulder, hip, and knee problems ranged from 1.3% to 8.5%. Construct-validity tests confirmed convergent and divergent validity of the ROMS. The tests also justified its additional value when the ROMS was used with joint-specific tools. When measuring test-retest reliability of the ROMS scales, intraclass correlation ranged from 0.80 to 0.90 at approximately one week and from 0.71 to 0.87 at approximately four weeks. Responsiveness of the ROMS was greater than that of the SF-12 and less than that of the joint-specific questionnaires. CONCLUSIONS: The ROMS is compatible with routine clinical process and has good psychometric properties in patients with shoulder, hip, and knee disorders. It can be used as a primary outcome tool for large observational studies and can supplement more specific tools in controlled studies. CLINICAL RELEVANCE: The ROMS was developed as a tool to measure and monitor the clinical status of the musculoskeletal system in a population of patients during and after treatment as well as over time.

Isolated adrenal hematoma presenting as acute right upper quadrant pain.

BACKGROUND: Adrenal hematoma is an infrequent occurrence in the setting of adult trauma care. It is typically associated with diffuse abdominal injury, and its presence is commonly correlated with high injury severity and mortality. OBJECTIVES: To discuss the recognition of adrenal hematoma as a cause of right upper quadrant pain. CASE REPORT: We present the case of a 23-year-old man who presented to the Emergency Department (ED) with acute right upper quadrant pain after blunt trauma to the area; he was initially diagnosed with an abdominal contusion with an incidental adrenal adenoma. After experiencing continued pain for 2 days, the patient returned to the ED for re-evaluation. Subsequent imaging revealed that the adrenal mass had enlarged, and it was determined that this patient had suffered an acute adrenal hematoma. The lesion was determined to be self-limited and the patient was treated with supportive care. Follow-up images 8 weeks later revealed resolution of the hematoma and the patient reported complete resolution of symptoms. We also discuss adrenal hematoma in the trauma setting and explain that in our patient, given the clinical scenario and statistical evidence, an initial diagnosis of adrenal hematoma should be favored over abdominal contusion with incidental adenoma. CONCLUSION: We describe a case of a traumatic isolated adrenal hematoma that presents acutely as right upper quadrant pain. This unusual presentation highlights the need for recognition of the adrenal gland as a potential cause of right upper quadrant pain in the trauma setting.