Team Approach: Osseointegration Amputation Surgery.

¼ The purpose of this article was to review the multidisciplinary, team-based approach necessary for the optimal management of patients with limb loss undergoing osseointegration surgery.¼ In this study, we describe the interdisciplinary process of screening, counseling, and surgical and rehabilitation considerations with an emphasis on principles rather than specific implants or techniques.¼ Integrated perioperative management and long-term surveillance are crucial to ensure the best possible outcomes.¼ We hope this model will service as an implant-agnostic guide to others seeking to development an osseointegration center of excellence.

What is the Case Volume of Orthopaedic Trauma Surgeons in the Military Health System? An Assessment of Wartime Readiness and Skills Sustainment.

INTRODUCTION: Complex, high-energy extremity trauma secondary to explosive mechanisms has been increasingly common in modern warfare, accounting for a majority of combat wounds throughout the conflicts in Iraq and Afghanistan. Fellowship-trained orthopaedic trauma surgeons treated many of these complex injuries; however, as the number of casualties continue to decrease during a period of relative peace, a growing concern over maintaining military trauma readiness exists. METHODS: The Military Health System Data Repository was queried for all Common Procedural Terminology (CPT) codes associated with 18 fellowship-trained orthopaedic trauma surgeons from 2013 to 2019. The codes were further analyzed and categorized based on common trauma subspecialty procedures such as fracture fixation of the pelvic ring, acetabulum, upper and lower extremity, peri-articular, and nonunion/malunion surgery. We used descriptive statistics to quantify both the average number of cases per surgeon per year in each of the subcategories and case volume among Military Treatment Facilities (MTFs) during the study period. RESULTS: We identified 7,769 CPT codes for surgical procedures throughout the study period. The most common surgical procedures performed were: removal of implant (n = 836, 11%), knee arthroscopy (n = 507, 7%), and debridement of devitalized tissue (n = 345, 4%). The total trauma subspecialty procedural codes and average cases per surgeon per year were as follows: pelvic ring (n = 54, <1 case/year), acetabulum (n = 90, 1 case/year), upper extremity (n = 1,314, 15 cases/year), lower extremity (n = 2,286, 25 cases/year), peri-articular (n = 675, 8 cases/year), and nonunion/malunion (n = 288, 3 cases/year). San Antonio Military Medical Center (SAMMC) accounted for the most fracture-related CPT codes overall (35%), while all other MTFs contributed approximately 10% or less of all fracture-related codes. CONCLUSIONS: These results highlight the lack of orthopaedic trauma volume at other MTFs outside of SAMMC, raising concern for maintaining military readiness during an inter-war period of relative peace. The DoD continues to make concerted efforts to maintain readiness through civilian partnerships and subsequently increase surgical case volume for military trauma surgeons. Future efforts should include an in-depth analysis of caseloads of military trauma surgeons providing care at both MTFs and civilian institutions to optimize preparedness in future conflicts.

Pain Management in Staged Osseointegration Procedures: A Retrospective Study and Foundation for Future Optimization.

INTRODUCTION: Osseointegration is an innovative procedure to attach an external prosthetic device directly to the skeleton. The technique has been shown to improve physical function and quality of life relative to conventional socket prosthetic devices. While much of the research in osseointegration has focused on functional outcomes, less is known regarding perioperative pain management. The purpose of this study was to describe perioperative and postoperative pain management approaches received by patients undergoing osseointegration procedures at a tertiary medical center. MATERIALS AND METHODS: This retrospective study was determined to be exempt from Institutional Review Board review by the Walter Reed National Military Medical Center Department of Research Programs. Perioperative and postoperative pain management approaches received by 41 patients who underwent 76 staged osseointegration procedures from 2016 to 2021 at Walter Reed National Military Medical Center were described. RESULTS: Pain management approaches included perioperative ketamine (51% stage I, 55% stage II), epidurals (76% stage I, 77% stage II) with a median of 3-4 days across stages, peripheral nerve catheters (27% stage I, 16% stage II), and/or single-shot peripheral nerve block (<10% across stages). The median morphine equivalent dose provided during surgery was 65 mg across both stages, with 56% and 54% of patients also requiring opioid medication in the post-anesthesia care unit. In 11 of 76 (15%) procedures, patients required an increase in the rate or concentration of epidural or peripheral nerve catheter infusion. In six (8%) unique recovery periods, patients experienced a dislodged catheter. In 27 of 76 (36%) unique recovery periods, patients experienced a significant increase in postoperative pain requiring acute pain service intervention in the form of catheter adjustment, intravenous pain medications, and/or the addition of intravenous patient-controlled analgesia. Adequate pain control was achieved with minimal epidural or peripheral nerve catheter trouble-shooting and a bolus for 24 patients (89% requiring intervention). Summed 24-hour pain scores (SPI24) did not vary across stages. SPI24 was positively correlated with opioid doses received. Patients with single, relative to multiple, limb amputations had similar SPI24 values (P > .05). CONCLUSIONS: Variability in pain management requirements calls forth opportunities to optimize osseointegration analgesia care and future research. As osseointegration becomes more accessible, the need for optimizing pain management through patient-centered research becomes more salient.

Deep Learning and Multimodal Artificial Intelligence in Orthopaedic Surgery.

This review article focuses on the applications of deep learning with neural networks and multimodal neural networks in the orthopaedic domain. By providing practical examples of how artificial intelligence (AI) is being applied successfully in orthopaedic surgery, particularly in the realm of imaging data sets and the integration of clinical data, this study aims to provide orthopaedic surgeons with the necessary tools to not only evaluate existing literature but also to consider AI's potential in their own clinical or research pursuits. We first review standard deep neural networks which can analyze numerical clinical variables, then describe convolutional neural networks which can analyze image data, and then introduce multimodal AI models which analyze various types of different data. Then, we contrast these deep learning techniques with related but more limited techniques such as radiomics, describe how to interpret deep learning studies, and how to initiate such studies at your institution. Ultimately, by empowering orthopaedic surgeons with the knowledge and know-how of deep learning, this review aspires to facilitate the translation of research into clinical practice, thereby enhancing the efficacy and precision of real-world orthopaedic care for patients.

Thighplasty at the Time of Stage-1 Bone-Anchored Osseointegration Surgery.

Background: For patients with transfemoral amputations and difficulty tolerating conventional socket-based prostheses, osseointegrated (OI) implants have enabled increased prosthetic use, improved patient satisfaction, and shown promising functional outcomes1,2. Although the use of OI implants effectively eliminates the soft-tissue-related challenges that have plagued socket-based prostheses, the presence of a permanent, percutaneous implant imparts a host of new soft-tissue challenges that have yet to be fully defined. In patients undergoing OI surgery who have redundant soft tissue, we perform a thighplasty to globally reduce excess skin and fat, tighten the soft-tissue envelope, and improve the contour of the residual limb. Description: First, the orthopaedic surgical team prepares the residual femur for implantation of the OI device. After the implant is inserted, the residual hamstrings and quadriceps musculature are closed over the end of the femur, and the subcutaneous tissue and skin are closed in a layered fashion. Although the anatomic location and amount of excess soft tissue are patient-dependent, we perform a standard pinch test to determine the amount of soft tissue that can be safely removed for the thighplasty. Once the proposed area of resection is marked, we proceed with longitudinal, sharp dissection down to the level of the muscular fascia. At this point, we use another pinch test to confirm the amount of soft-tissue resection that will allow for adequate resection without undue tension3. Excess subcutaneous fat and skin are carefully removed along the previously marked incisions, typically overlying the medial compartment of the thigh in the setting of patients with transfemoral amputations. The thighplasty incision is closed in a layered fashion over 1 or 2 Jackson-Pratt drains, depending on the amount of resection. Alternatives: Depending on the amount of redundant soft tissue, thighplasty may not be necessary at the time of OI surgery; however, in our experience, excess soft tissue surrounding the transcutaneous aperture can predispose the patient to increased shear forces at the aperture, increased drainage, and increased risk of infection4. Rationale: Although superficial infectious complications are most common following OI surgery, the need for soft-tissue refashioning and excision is one of the most common reasons for reoperation1,5. Our group has been more aggressive than most in our use of a vertical thighplasty procedure to globally reduce soft-tissue motion in the residual limb to avoid reoperation. Expected Outcomes: Although much of the OI literature has focused on infectious complications, recent studies have demonstrated reoperation rates of 18% to 36% for redundant soft tissue following OI surgery1,5. We believe that thighplasty at the time of OI not only reduces the likelihood of reoperation but may also decrease infectious complications by reducing relative motion and inflammation at the skin-implant interface4,6. Important Tips: The thighplasty procedure is ideally performed as part of the first stage of the OPRA (Osseointegrated Prosthesis for the Rehabilitation of Amputees) procedure to limit the likelihood of problematic ischemia-related complications.We utilize a confirmatory pinch test both before and throughout the thighplasty procedure to ensure adequate resection without undue tension.The thighplasty excision pattern utilizes a long vertical limb designed to decrease the circumferential laxity of the residual limb. Maximal tension is borne on the vertical limb and not on the transverse extensions, as these are prone to scar widening and distortion of surrounding tissues.Closed-suction drainage is utilized liberally to decrease the likelihood of a symptomatic seroma. Acronyms and Abbreviations: OI = osseointegratedOPRA = Osseointegrated Prosthesis for the Rehabilitation of AmputeesPVNS = pigmented villonodular synovitisT-GCT = tenosynovial giant-cell tumor.BMI = body mass indexPMH = past medical history.

Utility of Thermal Imaging in Predicting Superficial Infections in Transfemoral Osseointegrated Implants.

Background: Superficial infection is a common minor complication of transcutaneous implants that can be challenging to predict or diagnose. Although it remains unclear whether superficial infections progress to deep infections (which may require implant removal), predicting and treating any infection in these patients is important. Given that flap thinning during stage II surgery requires compromising vascularity for stability of the skin penetration aperture, we hypothesized that early skin temperature changes predict long-term superficial infection risk. Methods: We obtained standardized thermal imaging and recorded surface temperatures of the aperture and overlying flaps 2 weeks postoperatively for the first 34 patients (46 limbs) treated with the Osseointegrated Prosthesis for the Rehabilitation of Amputees transfemoral implant system. We used two-sided t tests to compare temperatures surrounding the aperture and adjacent soft tissues in patients with and without subsequent infection. Results: During median follow-up of 3 years, 14 limbs (30.4%) developed 23 superficial infections. At patients' initial 2-week visit, mean skin temperature surrounding the aperture was 36.3ºC in limbs that later developed superficial infections and 36.7ºC in uninfected limbs (P = 0.35). In four patients with bilateral implants who later developed superficial infection in one limb, average temperature was 1.5ºC colder in the infected limb (P = 0.12). Conclusions: Superficial infections remain a frequent complication of transfemoral osseointegration surgery. We did not find differences in early heat signatures between limbs subsequently complicated and those not complicated by superficial infection. Further research should explore more objective measures to predict, diagnose, and prevent infections after osseointegration surgery.

Life Expectancy After Treatment of Metastatic Bone Disease: An International Trend Analysis.

INTRODUCTION: The decision to treat metastatic bone disease (MBD) surgically depends in part on patient life expectancy. We are unaware of an international analysis of how life expectancy among these patients has changed over time. Therefore, we asked (1) how has the life expectancy for patients treated for MBD changed over time, and (2) which, if any, of the common primary cancer types are associated with longer survival after treatment of MBD? METHODS: We reviewed data collected from 2000 to 2022 in an international MBD database, as well as data used for survival model validation. We included 3,353 adults who underwent surgery and/or radiation. No patients were excluded. Patients were grouped by treatment date into period 1 (2000 to 2009), period 2 (2010 to 2019), and period 3 (2020 to 2022). Cumulative survival was portrayed using Kaplan-Meier curves; log-rank tests were used to determine significance at P < 0.05. Subgroup analyses by primary cancer diagnosis were performed. RESULTS: Median survival in period 2 was longer than in period 1 ( P < 0.001). Median survival (at which point 50% of patients survived) had not been reached for period 3. Median survival was longer in period 2 for all cancer types ( P < 0.001) except thyroid. Only lung cancer reached median survival in period 3, which was longer compared with periods 1 and 2 ( P < 0.001). Slow-growth, moderate-growth, and rapid-growth tumors all demonstrated longer median survival from period 1 to period 2; only rapid-growth tumors reached median survival for period 3, which was longer compared with periods 1 and 2 ( P < 0.001). DISCUSSION: Median duration of survival after treatment of MBD has increased, which was a consistent finding in nearly all cancer types. Longer survival is likely attributable to improvements in both medical and surgical treatments. As life expectancy for patients with MBD increases, surgical methods should be selected with this in mind. LEVEL OF EVIDENCE: VI.

Symptomatic Neuroma Development following En Bloc Resection of Skeletal and Soft-Tissue Tumors: A Retrospective Analysis of 331 Cases.

BACKGROUND: Although symptomatic neuroma formation has been described in other patient populations, these data have not been studied in patients undergoing resection of musculoskeletal tumors. This study aimed to characterize the incidence and risk factors of symptomatic neuroma formation following en bloc resection in this population. METHODS: The authors retrospectively reviewed adults undergoing en bloc resections for musculoskeletal tumors at a high-volume sarcoma center from 2014 to 2019. The authors included en bloc resections for an oncologic indication and excluded non-en bloc resections, primary amputations, and patients with insufficient follow-up. Data are provided as descriptive statistics, and multivariable regression modeling was performed. RESULTS: The authors included 231 patients undergoing 331 en bloc resections (female, 46%; mean age, 52 years). Nerve transection was documented in 87 resections (26%). There were 81 symptomatic neuromas (25%) meeting criteria of Tinel sign or pain on examination and neuropathy in the distribution of suspected nerve injury. Factors associated with symptomatic neuroma formation included age 18 to 39 [adjusted OR (aOR), 3.6; 95% CI, 1.5 to 8.4; P < 0.01] and 40 to 64 (aOR, 2.2; 95% CI, 1.1 to 4.6; P = 0.04), multiple resections (aOR, 3.2; 95% CI, 1.7 to 5.9; P < 0.001), preoperative neuromodulator requirement (aOR, 2.7; 95% CI, 1.2 to 6.0; P = 0.01), and resection of fascia or muscle (aOR, 0.5; 95% CI, 0.3 to 1.0; P = 0.045). CONCLUSION: The authors' results highlight the importance of adequate preoperative optimization of pain control and intraoperative prophylaxis for neuroma prevention following en bloc resection of tumors, particularly for younger patients with a recurrent tumor burden. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Functional outcomes after open reconstruction or nonoperative management of 81 pathologic acetabular fractures from metastatic bone disease.

Background: Pathologic acetabular fracture secondary to skeletal metastasis may result in debilitating pain, inability to ambulate, and impaired quality of life, which may mark the first period of dependent care in cancer patients. Acetabular reconstruction may involve morbid procedures with increased complication rates. This study aimed to evaluate the evolution of pain, performance status, and ambulation following nonoperative management or open reconstruction of pathologic acetabular fractures. Methods: A retrospective cohort of 2630 adult patients with osseous metastatic disease treated at a high-volume cancer center between 2005 and 2021 was screened for pathologic fractures of the acetabulum. The study outcomes were pain, performance status, and the ability to ambulate. We identified 78 patients (median age, 60 years; 37 female patients [46%]) with 81 fractures. Of these, treatment consisted of open reconstruction (n = 34) or nonoperative management alone (n = 47). The mean follow-up in surviving patients was 3.4 years. Results: Open reconstruction was performed more frequently for displaced fractures (P < 0.01), Harrington class III or IV acetabula (P < 0.01), and patients with a performance status ≥3 at hospitalization (P = 0.00). Open reconstruction was associated with clinically meaningful improvements in pain (adjusted odds ratio [aOR], 8.3; 95% CI, 1.4-50.6; P = 0.02) and performance status (aOR, 10.9; 95% CI, 1.7-71.0; P = 0.01) at discharge and a restoration of ambulation (aOR, 7.5; 95% CI, 1.9-29.8; P < 0.01) at final follow-up. Conclusions: In patients with pathologic acetabular fracture due to osseous metastatic disease, functional improvements in pain, performance status, and ambulation were observed following open acetabular reconstruction in carefully selected patients, with no impact on survival, while noninferior improvements were observed in patients receiving nonoperative management when considering their larger clinical context. Level of evidence: Level III, therapeutic study.

Incidence of and Risk Factors for Thromboembolism After Endoprosthetic Reconstruction in Musculoskeletal Oncology Patients.

BACKGROUND: The aim of the present study was to assess the incidence of and risk factors for thromboembolic events-including assessment of the intraoperative use of tranexamic acid and postoperative use of chemical thromboprophylaxis-in patients undergoing operative treatment of primary bone or soft-tissue sarcoma or oligometastatic bone disease. METHODS: This study was performed as a secondary analysis of prospective data collected from the Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) randomized controlled trial, which included 604 patients ≥12 years old who underwent surgical resection and endoprosthetic reconstruction for either primary bone or soft-tissue sarcoma or oligometastatic disease of the femur or tibia. We determined the incidence of thromboembolic events in these patients and evaluated potential risk factors, including patient age, sex, antibiotic treatment group, type of tumor (i.e., primary bone or soft-tissue sarcoma or metastatic bone disease), intraoperative tranexamic acid, tourniquet use, operative time, pathologic characteristics (i.e., American Joint Committee on Cancer grade, vascular invasion, and percent necrosis), postoperative chemical thromboprophylaxis regimen, and surgical site infection. Continuous variables were assessed with use of the Student t test. Categorical variables were assessed with use of the Pearson chi-square test, except when the expected cell counts were <5, in which case the Fisher exact test was utilized. Significance was set at 0.05. RESULTS: Postoperative thromboembolic events occurred in 11 (1.8%) of 604 patients. Patients who experienced a thromboembolic event had a significantly higher mean (± standard deviation) age (59.6 ± 17.5 years) than those who did not experience a thromboembolic event (40.9 ± 21.8; p = 0.002). Patients randomized to the long-term antibiotic group had a significantly higher incidence of thromboembolic events (9 of 293; 3.1%) than those randomized to the short-term antibiotic group (2 of 311; 0.64%; p = 0.03). Neither intraoperative tranexamic acid nor postoperative chemical thromboprophylaxis were significantly associated with the occurrence of a thromboembolic event. CONCLUSIONS: Although relatively rare in the PARITY cohort, thromboembolic events were more likely to occur in older patients and those receiving long-term prophylactic antibiotics. Intraoperative tranexamic acid and postoperative chemical thromboprophylaxis were not associated with a greater incidence of thromboembolic events. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Does the Use of Negative Pressure Wound Therapy and Postoperative Drains Impact the Development of Surgical Site Infections?: A PARITY Trial Secondary Analysis.

BACKGROUND: Surgical site infections (SSIs) represent a major complication following oncologic reconstructions. Our objectives were (1) to assess whether the use of postoperative drains and/or negative pressure wound therapy (NPWT) were associated with SSIs following lower-extremity oncologic reconstruction and (2) to identify factors associated with the duration of postoperative drains and with the duration of NPWT. METHODS: This is a secondary analysis of the Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) trial, a multi-institution randomized controlled trial of lower-extremity oncologic reconstructions. Data were recorded regarding the use of drains alone, NPWT alone, or both NPWT and drains, including the total duration of each postoperatively. We analyzed postoperative drain duration and associations with tourniquet use, intraoperative thromboprophylaxis or antifibrinolytic use, incision length, resection length, and total operative time, through use of a linear regression model. A Cox proportional hazards model was used to evaluate the independent predictors of SSI. RESULTS: Overall, 604 patients were included and the incidence of SSI was 15.9%. Postoperative drains alone were used in 409 patients (67.7%), NPWT alone was used in 15 patients (2.5%), and both postoperative drains and NPWT were used in 68 patients (11.3%). The median (and interquartile range [IQR]) duration of drains and of NPWT was 3 days (IQR, 2 to 5 days) and 6 days (IQR, 4 to 8 days), respectively. The use of postoperative drains alone, NPWT alone, or both drains and NPWT was not associated with SSI (p = 0.14). Increased postoperative drain duration was associated with longer operative times and no intraoperative tourniquet use, as shown on linear regression analysis (p < 0.001 and p = 0.03, respectively). A postoperative drain duration of ≥14 days (hazard ratio [HR], 3.6; 95% confidence interval [CI], 1.3 to 9.6; p = 0.01) and an operative time of ≥8 hours (HR, 4.5; 95% CI, 1.7 to 11.9; p = 0.002) were independent predictors of SSI following lower-extremity oncologic reconstruction. CONCLUSIONS: A postoperative drain duration of ≥14 days and an operative time of ≥8 hours were independent predictors of SSI following lower-extremity oncologic reconstruction. Neither the use of postoperative drains nor the use of NPWT was a predictor of SSI. Future research is required to delineate the association of the combined use of postoperative drains and NPWT with SSI. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Bone Homeostasis and Physiology in Normal and Orthopaedic Disease Conditions.

Some of the most common human systemic diseases-both benign and malignant-affect bone regulation, formation, and homeostasis (the cellular balance regulated by osteocytes, osteoblasts, and osteoclasts). This review discusses our current understanding of the molecular components and mechanisms that are responsible for homeostasis and interactions resulting in dysregulation (dysfunction due to the loss of the dynamic equilibrium of bone homeostasis). Knowledge of key pathways in bone biology can improve surgeon understanding, clinical recognition, and treatment of bone homeostasis-related diseases.

Central role for neurally dysregulated IL-17A in dynamic networks of systemic and local inflammation in combat casualties.

Dynamic Network Analysis (DyNA) and Dynamic Hypergraphs (DyHyp) were used to define protein-level inflammatory networks at the local (wound effluent) and systemic circulation (serum) levels from 140 active-duty, injured service members (59 with TBI and 81 non-TBI). Interleukin (IL)-17A was the only biomarker elevated significantly in both serum and effluent in TBI vs. non-TBI casualties, and the mediator with the most DyNA connections in TBI wounds. DyNA combining serum and effluent data to define cross-compartment correlations suggested that IL-17A bridges local and systemic circulation at late time points. DyHyp suggested that systemic IL-17A upregulation in TBI patients was associated with tumor necrosis factor-α, while IL-17A downregulation in non-TBI patients was associated with interferon-γ. Correlation analysis suggested differential upregulation of pathogenic Th17 cells, non-pathogenic Th17 cells, and memory/effector T cells. This was associated with reduced procalcitonin in both effluent and serum of TBI patients, in support of an antibacterial effect of Th17 cells in TBI patients. Dysregulation of Th17 responses following TBI may drive cross-compartment inflammation following combat injury, counteracting wound infection at the cost of elevated systemic inflammation.

Venous malformation may be a feature of EXT1-related hereditary multiple exostoses: A report of two unrelated probands.

Hereditary multiple exostoses (HME), also known as hereditary multiple osteochondroma (HMO), is an autosomal dominant disorder caused by pathogenic variants in exostosin-1 or -2 (EXT1 or EXT2). It is characterized by the formation of multiple benign growing osteochondromas (exostoses) that most commonly affect the long bones; however, it may also occur throughout the body. Although many of these lesions are clinically asymptomatic, some can lead to chronic pain and skeletal deformities and interfere with adjacent neurovascular structures. Here, we report two unrelated probands that presented with a clinical and molecular diagnosis of HME with venous malformation, a clinical feature not previously reported in individuals with HME.

External validation of the PATHFx decision-support tool on Turkish patients with skeletal metastasis.

Objective: Accurate determination of life expectancy becomes very important when determining the treatment of patients with pathologic fractures. We aimed to investigate the predictive role of the PATHFx model in Turkish patients by estimating the area under curve (AUC) of the receiver operator characteristic (ROC) and externally validating the results of PATHFx on the Turkish population. Methods: The data of 122 patients who presented to one of four orthopaedic oncology referral centres in Istanbul (2010-2017) and underwent surgical management of pathologic fractures were retrospectively collected. Patients were evaluated according to age, sex, type of pathologic fracture, presence of organ metastasis, presence of lymph node metastasis, haemoglobin concentration at presentation, primary oncologic diagnosis, number of bone metastases, and Eastern Cooperative Oncology Group (ECOG) status. Estimations of the PATHFx program by months were statistically evaluated using ROC analysis. Results: In our study population (122 patients), all survived the first month, 102 survived the third month, 89 were alive at 6 months, and 58 patients survived at 12 months. At 18 and 24 months, 39 and 27 patients were alive, respectively. The AUC value was 0.677 at 3 months, 0.695 at 6 months, 0.69 at 12 months, 0.674 at 18 months, and 0.693 at 24 months. The 3-, 6-, 12-, 18-, and 24-month survival rates were statistically significant (P < 0.01 and P < 0.05). ECOG performance status was 0-2 points in 33 patients (Memorial Sloan-Kettering Cancer Center (MSKCC) data set: 93 cases, our data set: 33 cases). ECOG performance status was 3-4 points in 89 patients (MSKCC data set: 96 cases, our data set: 89 cases). Conclusions: The objective data used by PATHFx for prediction provided statistically accurate estimates on Turkish patients, who are presumed to have mixed genomes through history from both Europe and Asia, and demonstrates its applicability to the Turkish population.

Is the Lifetime Malignancy Risk in United States Military Personnel Sustaining Combat-related Trauma Increased Because of Radiation Exposure From Diagnostic Imaging?

BACKGROUND: Patients with complex polytrauma in the military and civilian settings are often exposed to substantial diagnostic medical radiation because of serial imaging studies for injury diagnosis and subsequent management. This cumulative radiation exposure may increase the risk of subsequent malignancy. This is particularly true for combat-injured servicemembers who receive care at a variety of facilities worldwide. Currently, there is no coordinated effort to track the amount of radiation exposure each servicemember receives, nor a surveillance program to follow such patients in the long term. It is important to assess whether military servicemembers are exposed to excessive diagnostic radiation to mitigate or prevent such occurrences and monitor for carcinogenesis, when necessary. The cumulative amount of radiation exposure for combat-wounded and noncombat-wounded servicemembers has not been described, and it remains unknown whether diagnostic radiation exposure meets thresholds for an increased risk of carcinogenesis. QUESTIONS/PURPOSES: We performed this study to (1) quantify the amount of exposure for combat-wounded servicemembers based on medical imaging in the first year after injury and compare those exposures with noncombat-related trauma, and (2) determine whether the cumulative dose of radiation correlates to the Injury Severity Score (ISS) across the combat-wounded and noncombat-wounded population combined. METHODS: We performed a retrospective study of servicemembers who sustained combat or noncombat trauma and were treated at Walter Reed National Military Medical Center from 2005 to 2018. We evaluated patients using the Department of Defense Trauma Registry. After consolidating redundant records, the dataset included 3812 unique servicemember encounters. Three percent (104 of 3812) were excluded because of missing radiation exposure data in the electronic medical record. The final cohort included 3708 servicemembers who had combat or noncombat injury trauma, with a mean age at the time of injury of 26 ± 6 years and a mean ISS of 18 ± 12. The most common combat trauma mechanisms of injury were blast (in 65% [2415 of 3708 patients]), followed by high-velocity gunshot wounds (in 22% [815 of 3708 patients]). We calculated the cumulative diagnostic radiation dose exposure at 1 year post-traumatic injury in patients with combat-related trauma and those with noncombat trauma. We did this by multiplying the number of imaging studies by the standardized effective radiation dose for each imaging study type. We then performed analysis of variance for four data subsets (battle combat trauma, nonbattle civilian trauma, high ISS, and high radiation exposure [> 50 mSv]) independently. To evaluate whether the total number of imaging studies, radiation exposure, and ISS values differed between battle-wounded and nonbattle-wounded patients, we performed a pairwise t-test. RESULTS: The mean radiation exposure for combat-related injuries was 35 ± 26 mSv while the mean radiation exposure for noncombat-related injuries was 22 ± 33 mSv in the first year after injury. In the first year after trauma, 44% of patients (1626 of 3708) were exposed to high levels of radiation that were greater than 20 mSv, and 23% (840 of 3708) were exposed to very high levels of radiation that were greater than 50 mSv. Servicemembers with combat trauma-related injuries had eight more imaging studies than those who sustained noncombat injuries. Servicemembers with combat trauma injuries (35 ± 26 mSv) were exposed to more radiation (approximately 4 mSv) than patients treated for noncombat injuries (22 ± 33 mSv) (p = 0.01). We found that servicemembers with combat injuries had a higher ISS than servicemembers with noncombat trauma (p < 0.001). We found a positive correlation between radiation exposure and ISS for servicemembers. The positive relationship between radiation exposure and ISS held for combat trauma (r 2 = 0.24; p < 0.001), noncombat trauma (r 2 = 0.20; p < 0.001), servicemembers with a high ISS (r 2 = 0.10; p < 0.001), and servicemembers exposed to high doses of radiation (r 2 = 0.09; p < 0.001). CONCLUSION: These data should be used during clinical decision-making and patient counseling at military treatment facilities and might provide guidance to the Defense Health Agency. These recommendations will help determine whether the benefits of further imaging outweigh the risk of carcinogenesis. If not, we need to develop interdisciplinary clinical practice guidelines to reduce or minimize radiation exposure. It is important for treating physicians to seriously weigh the risk and benefits of every imaging study ordered because each test does not come without a cumulative risk. LEVEL OF EVIDENCE: Level III, therapeutic study.

Can a Bayesian belief network for survival prediction in patients with extremity metastases (PATHFx) be externally validated in an Asian cohort of 356 surgically treated patients?

BACKGROUND AND PURPOSE: Predicted survival may influence the treatment decision for patients with skeletal extremity metastasis, and PATHFx was designed to predict the likelihood of a patient dying in the next 24 months. However, the performance of prediction models could have ethnogeographical variations. We asked if PATHFx generalized well to our Taiwanese cohort consisting of 356 surgically treated patients with extremity metastasis. PATIENTS AND METHODS: We included 356 patients who underwent surgery for skeletal extremity metastasis in a tertiary center in Taiwan between 2014 and 2019 to validate PATHFx's survival predictions at 6 different time points. Model performance was assessed by concordance index (c-index), calibration analysis, decision curve analysis (DCA), Brier score, and model consistency (MC). RESULTS: The c-indexes for the 1-, 3-, 6-, 12-, 18-, and 24-month survival estimations were 0.71, 0.66, 0.65, 0.69, 0.68, and 0.67, respectively. The calibration analysis demonstrated positive calibration intercepts for survival predictions at all 6 timepoints, indicating PATHFx tended to underestimate the actual survival. The Brier scores for the 6 models were all less than their respective null model's. DCA demonstrated that only the 6-, 12-, 18-, and 24-month predictions appeared useful for clinical decision-making across a wide range of threshold probabilities. The MC was < 0.9 when the 6- and 12-month models were compared with the 12-month and 18-month models, respectively. INTERPRETATION: In this Asian cohort, PATHFx's performance was not as encouraging as those of prior validation studies. Clinicians should be cognizant of the potential decline in validity of any tools designed using data outside their particular patient population. Developers of survival prediction tools such as PATHFx might refine their algorithms using data from diverse, contemporary patients that is more reflective of the world's population.

Quantitative preoperative patient assessments are related to survival and procedure outcome for osseous metastases.

Aims: Our objective was to determine if preoperative patient-reported assessments are associated with survival after surgery for stabilization of skeletal metastases. Patients and Methods: All patients with metastatic cancer to bone and indications for skeletal stabilization surgery were approached to participate in a prospective cohort study at a tertiary care center from 2012 to 2017. Of the 208 patients who were eligible, 195 (94%) completed the 36-item Short Form Health Survey (SF-36) preoperatively and underwent surgical treatment of skeletal metastases with complete or impending fractures; the sample encompassed a range of cancer diagnoses and included cases of both internal fixation and endoprosthetic replacement. Cox proportional hazards models were used to identify associations between SF-36 scores and survival. Results: In a model adjusted for clinical factors, patients' mental and physical SF-36 component summary scores were significantly associated with survival, as was their SF-36 composite score (P = 0.004, P = 0.015, and P < 0.001, respectively). Scores in the general health, vitality, and mental health domains were each strongly associated with survival (P < 0.001). Conclusions: Patients' preoperative assessments of their health status are associated with their survival after surgery for skeletal metastases. Patient-reported assessments have the potential to contribute unique information to models that estimate patient survival, as part of efforts to provide optimal, individualized care and make informed decisions about the type and magnitude of surgery for metastatic bone disease that will last the patient's lifetime.

Machine learning algorithms to estimate 10-Year survival in patients with bone metastases due to prostate cancer: toward a disease-specific survival estimation tool.

BACKGROUND: Prognostic indicators, treatments, and survival estimates vary by cancer type. Therefore, disease-specific models are needed to estimate patient survival. Our primary aim was to develop models to estimate survival duration after treatment for skeletal-related events (SREs) (symptomatic bone metastasis, including impending or actual pathologic fractures) in men with metastatic bone disease due to prostate cancer. Such disease-specific models could be added to the PATHFx clinical-decision support tool, which is available worldwide, free of charge. Our secondary aim was to determine disease-specific factors that should be included in an international cancer registry. METHODS: We analyzed records of 438 men with metastatic prostate cancer who sustained SREs that required treatment with radiotherapy or surgery from 1989-2017. We developed and validated 6 models for 1-, 2-, 3-, 4-, 5-, and 10-year survival after treatment. Model performance was evaluated using calibration analysis, Brier scores, area under the receiver operator characteristic curve (AUC), and decision curve analysis to determine the models' clinical utility. We characterized the magnitude and direction of model features. RESULTS: The models exhibited acceptable calibration, accuracy (Brier scores < 0.20), and classification ability (AUCs > 0.73). Decision curve analysis determined that all 6 models were suitable for clinical use. The order of feature importance was distinct for each model. In all models, 3 factors were positively associated with survival duration: younger age at metastasis diagnosis, proximal prostate-specific antigen (PSA) < 10 ng/mL, and slow-rising alkaline phosphatase velocity (APV). CONCLUSIONS: We developed models that estimate survival duration in patients with metastatic bone disease due to prostate cancer. These models require external validation but should meanwhile be included in the PATHFx tool. PSA and APV data should be recorded in an international cancer registry.